Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity
Open accessAbstract
Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy. Apart of the known factors involved in fusion, OPA1 and mitofusins, and fission, DRP1 and FIS1, emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation. Mitochondria is also affected by sexual hormones that suffer drastic changes during ageing. The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver. In this article, the role of mitochondrial homeostasis in ageing and age-dependent fat accumulation is revised. This review highlights the importance of mitochondria in the accumulation of fat during ageing and related diseases such as obesity, metabolic syndrome or type 2 diabetes mellitus.
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TL;DR
This narrative review argues that mitochondrial dysfunction sits at the centre of age-dependent fat accumulation, linking the mTOR/AMPK/sirtuin nutrient-sensing network to mitochondrial biogenesis, fusion/fission dynamics and mito-/autophagy. It contrasts the fusion-prone, giant-mitochondria phenotype of ageing with the fission-driven, small damaged mitochondria seen in obesity and high-fat feeding, and adds hormonal, inflammatory and newly described peptide regulators to the picture.
Key findings
- Three major nutritional sensors — mTOR, AMPK and sirtuins — control mitochondrial biogenesis, dynamics (fusion via OPA1/mitofusins, fission via DRP1/FIS1) and turnover through mito- and autophagy; AMPK and SIRT1 modulate PGC1α by phosphorylation and deacetylation respectively.
- Ageing and obesity diverge in mitochondrial morphology: ageing is associated with accumulation of giant, highly interconnected dysfunctional mitochondria (reported in human lymphocytes and mouse cells), whereas fat accumulation and obesity are associated with increased fission, fragmentation and reduced Mfn2, producing small, low-potential mitochondria.
- Reduced Mfn2 expression is reported in skeletal muscle of both obese and T2DM patients, with the reduction directly proportional to BMI and inversely proportional to insulin response (Pich et al., 2005, as cited).
- A study of 248 non-diabetic participants from the Baltimore Longitudinal Study of Aging is cited as associating impaired mitochondrial capacity with greater insulin resistance (Fabbri et al., 2016).
- Emerging regulators are highlighted: prohibitins (PHB-1/PHB-2, linked to OPA1 stabilization and, when overexpressed in adipocytes, to obesity development in mice), sestrins (Sesn2/Sesn3, AMPK activation and mTORC1 repression), and mitochondrial-derived peptides MOTS-c and humanin (a 24-amino-acid peptide) with protective effects against age- and diet-induced insulin resistance and obesity in mice.
- Oestrogen decline during ageing is proposed as a key driver of mitochondrial dysfunction and fat redistribution, via effects on PGC1α, fusion genes and prohibitin expression; rising FSH is also linked to visceral fat accumulation.
- Mitochondrial dysfunction is proposed to activate the NLRP3 inflammasome via ROS, creating a vicious cycle with caspase-1, fat cell senescence and SASP.
Methods
- Narrative review; no primary experimental data, systematic search strategy or meta-analysis is described.
- Evidence is synthesised from cited animal models (mice, rats, *Drosophila*, *C. elegans*) and human studies (skeletal muscle, liver, adipose tissue, breast cancer cell lines, POMC/NPY-Agrp neurons).
- Organised thematically: molecular regulation of mitochondrial physiology; ageing effects on activity and turnover; age-dependent fat accumulation; metabolic syndrome; inflammation; sexual hormones; and hypothalamic control of satiety.
Limitations
- Stated by the paper: the factors controlling changes in mitochondrial dynamics during ageing "have not been determined yet"; whether mitochondrial dysfunction causes or is a consequence of fat accumulation "is not clear"; the role of mitochondria in muscle in high-fat-diet-induced T2DM "is not completely clear," with discrepant rat studies showing either reduced or increased mitochondrial content and lipid oxidation; and no information is available on sestrin activity in adipose tissue or its behaviour during ageing, with no human studies performed yet.
- Evident from the text: as a narrative review it presents no new data, and several key claims (e.g., sestrins as regulators of fat accumulation, oestrogen–mitochondria links in fat) rest on indirect or hypothetical evidence the author himself flags as requiring further study; the manuscript also appears in a pre-publication form containing tracked reviewer-response text and grammatical inconsistencies.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 317 cited sources checked · 0 supported · 0 flagged
- Findingcitation§ Inflammation and lipid accumulation.
NLRP3 activity increases in mouse liver during ageing.
“In fact, we have recently found that NLRP3 activity increases in mouse liver during ageing but this activity is inhibited by RSV probably by reducing the level of oxidative stress increasing the mitochondrial turnover and eliminating by this mechanism ROS-producing deficient mitochondria (Baur et al., 2006; Tung et al., 2015a).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Baur et al., 2006 source
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- cites Tung et al., 2015a
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- Findingcitation§ Inflammation and lipid accumulation.
NLRP3 activity in mouse liver during ageing is inhibited by resveratrol.
“In fact, we have recently found that NLRP3 activity increases in mouse liver during ageing but this activity is inhibited by RSV probably by reducing the level of oxidative stress increasing the mitochondrial turnover and eliminating by this mechanism ROS-producing deficient mitochondria (Baur et al., 2006; Tung et al., 2015a).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Baur et al., 2006 source
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- cites Tung et al., 2015a
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- Findingcitation§ Inflammation and lipid accumulation.
NLRP3 activity in mouse liver during ageing is inhibited by RSV.
“this activity is inhibited by RSV”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Baur et al., 2006 source
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- cites Tung et al., 2015a
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- Premisecitation§ Introduction
Obesity is associated with adipose tissue dysfunction characterized by adipocyte hypertrophy, proinflammatory processes, impaired insulin signalling and insulin resistance.
“Obesity is associated with adipose tissue dysfunction characterized by adipocyte hypertrophy, proinflammatory processes, impaired insulin signalling and insulin resistance”
- Also stated in: § Introduction · plain
“Obesity is associated with adipose tissue dysfunction characterized by adipocyte hypertrophy, proinflammatory processes, impaired insulin signalling and insulin resistance (Karakelides et al., 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Karakelides et al., 2010 source
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- Also stated in: § Introduction · plain
- Premisenone given§ Regulation of AMPK and mTOR controls energy metabolism.
AMPK stimulates cellular catabolism of sugars, proteins and lipids.
“AMPK stimulates cellular catabolism of sugars, proteins and lipids.”
- Also stated in: § Regulation of AMPK and mTOR controls energy metabolism. · plain
“AMPK stimulates cellular catabolism of sugars, proteins and lipids.”
Quote in the paperNot a substantial claim - Also stated in: § Regulation of AMPK and mTOR controls energy metabolism. · plain
- Premisecitation§ Introduction
Their dedifferentiation occurs by the decrease of adipogenic factors such as C/EBPalpha and PPAR-γ, a known mitochondrial regulator.
“Their dedifferentiation occurs by the decrease of adipogenic factors such as CCAAT/enhancer binding alpha (C/EBPalpha) and peroxisome proliferator activated receptor gamma (PPAR-γ), a known mitochondrial regulator”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kirkland et al., 2002 source
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- Premisenone given§ Introduction
Mitochondrial activity is modulated by the availability of energy in cells.
“Their activity is modulated by the availability of energy in cells.”
- Also stated in: § Introduction · plain
“Their activity is modulated by the availability of energy in cells.”
Quote in the paperNot a substantial claim - Also stated in: § Introduction · plain
- Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.
Sirtuins act as metabolic sensors by detecting fluctuations in the NAD+/NADH ratio in cells.
“Sirtuins also act as metabolic sensors by detecting fluctuations in the NAD + /NADH ratio in cells.”
Quote in the paperNot a substantial claim - Premisecitation§ Introduction
Mitochondrial dysfunction is associated with the functional decline found in tissues and organs during ageing.
“Mitochondrial dysfunction is associated with the functional decline found in tissues and organs during ageing”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Riera et al., 2016 source
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- Premisecitation§ Introduction
In 248 non-diabetic participants from the Baltimore Longitudinal Study of Aging, impaired mitochondrial capacity was associated with greater insulin resistance.
“a study carried out with 248 non-diabetic participants from the Baltimore Londigutinal Study of Aging has associated impaired mitochondrial capacity with greater insulin resistance”
- Also stated in: § Introduction · plain
“Recently, a study carried out with 248 non-diabetic participants from the Baltimore Londigutinal Study of Aging has associated impaired mitochondrial capacity with greater insulin resistance (Fabbri et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Fabbri et al., 2016
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- Also stated in: § Introduction · plain
- Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
AMPK inhibits by phosphorylation several anabolic enzymes such as ACC, GAPT, HMGCR and GS, affecting glycogen and lipid biosynthesis.
“AMPK inhibits by phosphorylation several anabolic enzymes such as acetyl-coenzyme A (CoA) carboxylase (ACC), glycerol phosphate acyl transferase (GAPT), 3-hydroxyl-3-methylglutaryl CoA reductase (HMGCR) and glycogen synthase (GS) affecting glycogen and lipid biosynthesis”
- Also stated in: § Regulation of AMPK and mTOR controls energy metabolism. · plain
“AMPK inhibits by phosphorylation several anabolic enzymes such as acetyl-coenzyme A (CoA) carboxylase (ACC), glycerol phosphate acyl transferase (GAPT), 3-hydroxyl-3-methylglutaryl CoA reductase (HMGCR) and glycogen synthase (GS) affecting glycogen and lipid biosynthesis (Hardie et al., 2012).”
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- Also stated in: § Regulation of AMPK and mTOR controls energy metabolism. · plain
- Premisenone given§ Introduction
Key regulators of metabolism affect mitochondrial activity, dynamics and turnover.
“Key regulators of metabolism not only affect the activity of mitochondria but also their dynamics and turnover.”
- Also stated in: § Introduction · plain
“Key regulators of metabolism not only affect the activity of mitochondria but also their dynamics and turnover.”
Quote in the paperSubstantial claim - Also stated in: § Introduction · plain
- Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.
eNOS is induced by calorie restriction in mice and human muscle.
“eNOS is induced by CR in mice and human muscle”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
AMPK inhibits the transcriptional activity of SREBP, decreasing the expression of genes involved in fatty acid synthesis.
“AMPK also inhibits the transcriptional activity of sterol regulatory element binding protein (SREBP) decreasing the expression of genes involved in fatty acid synthesis”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Li et al., 2011
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- Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.
SIRT1 activates eNOS by deacetylation in human vascular cells.
“SIRT1 has been suggested to play an important role since this enzyme activates eNOS by deacetylation in human vascular cells”
- Also stated in: § Molecular mechanisms involved in the regulation of mitochondrial physiology. · hedged
“SIRT1 has been suggested to play an important role since this enzyme activates eNOS by deacetylation in human vascular cells (Mattagajasingh et al., 2007).”
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- Also stated in: § Molecular mechanisms involved in the regulation of mitochondrial physiology. · hedged
- Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.
SIRT3, a mitochondrial sirtuin, plays a very important role in the regulation of mitochondrial activity, especially in fat metabolism.
“SIRT3, a member located in the mitochondria, seems to a very important role in the regulation of mitochondrial activity especially in fat metabolism”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Kendrick et al., 2011 source
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- Premisenone given§ Molecular mechanisms involved in the regulation of mitochondrial physiology.
Mitochondrial physiology, dynamics and turnover respond to the relationship between the activities of key regulators of cell metabolism.
“Mitochondrial physiology, dynamics and turnover respond to the relationship between the activities of key regulators of cell metabolism.”
Quote in the paperSubstantial claim - Interpretationnone given§ Regulation of AMPK and mTOR controls energy metabolism.
Control of mitochondrial biogenesis and turnover through AMPK and mTOR activities is key in the regulation of cell metabolism and mitochondria.
“Control of mitochondrial biogenesis and turnover through AMPK and mTOR activities is key in the regulation cell metabolism and, in particular, mitochondria.”
Quote in the paperNot a substantial claim - Interpretationcitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Mitochondrial dysfunction plays an important role in obesity and obesity-related diseases such as insulin resistance and fatty liver.
“A considerable body of evidence demonstrate that mitochondrial dysfunction also plays an important role in obesity and obesity-related diseases such as insulin resistance and fatty liver.”
- Also stated in: § Mitochondrial dysfunction is associated with age-dependent fat accumulation. · boosted
“A considerable body of evidence demonstrate that mitochondrial dysfunction also plays an important role in obesity and obesity-related diseases such as insulin resistance and fatty liver.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Putti et al., 2015 source
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- cites Wang et al., 2013 source
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- Rests on an assumption: Mitochondrial dysfunction is a cause, not merely a consequence, of fat accumulation and insulin resistance.
- Also stated in: § Mitochondrial dysfunction is associated with age-dependent fat accumulation. · boosted
- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
MOTS-C activates AMPK.
“The short open reading frame found within the mitochondrial 12S rRNA known as MOTS-C (mitochondrial open reading frame of the 12S rRNA-c) appears mainly in skeletal muscle and activate AMPK (Lee et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lee et al., 2016 source
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- Interpretationcitation§ Regulation of AMPK and mTOR controls energy metabolism.
AMPK and mTORC1 have contrary effects on autophagy and mitophagy.
“AMPK and mTORC1 regulation is their contrary effect on autophagy and mitophagy”
Quote in the paperNot a substantial claim - Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Obesity and T2DM are associated with mitochondrial dysfunction indicated by low expression of mtDNA and reduction of OXPHOS proteins in rodents and humans.
“In several of the models studied including rodents and humans, these diseases are associated with mitochondrial dysfunction indicated by low expression of mtDNA and reduction of the levels of proteins involved in oxidative phosphorylation (OXPHOS).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Patti and Corvera, 2010 source
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- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
Humanin is able to restore mitochondrial function after oxidative injury in retinal pigment epithelial cells.
“Humanin has demonstrated protective capacity in age-related diseases such as T2DM and Alzheimer's disease (Mahboobi et al., 2014) and is able to restore mitochondrial function after oxidative injury in retinal pigment epithelial cells (Sreekumar et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sreekumar et al., 2016 source
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- Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
mTORC1 negatively regulates autophagy through phosphorylating ULK-1 and ULK-2 in inhibitory sites.
“mTORC1 negatively regulates autophagy through phosphorylating the mediators, unc-51-like kinase 1/2 (ULK-1 and ULK-2), in inhibitory sites”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
AMPK positively regulates autophagy by phosphorylating ULK-1 and ULK-2 in their activating sites.
“AMPK positively regulates autophagy by phosphorylating these proteins in their activating sites”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Alers et al., 2012 source
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- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
Defects in mitochondrial activity activate a retrograde response that communicates mitochondrial dysfunction to the nucleus through activation of the AMPK/PGC1α signalling axis.
“Defects in mitochondrial activity activate a retrograde response that communicat mitochondrial dysfunction to nucleus through activation of AMPK/PGC1α signalling axis (Quiros et al., 2016).”
- Also stated in: § Mitochondrial turnover can be regulated by different factors during ageing. · plain
“Defects in mitochondrial activity activate a retrograde response that communicat mitochondrial dysfunction to nucleus through activation of AMPK/PGC1α signalling axis (Quiros et al., 2016).”
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- Also stated in: § Mitochondrial turnover can be regulated by different factors during ageing. · plain
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Induction of mitochondrial dysfunction by blocking respiration or knocking down mitochondrial transcription factor A induces insulin resistance in human adipocytes.
“Further, induction of mitochondrial dysfunction by blocking respiration or knocking down the mitochondrial transcription factor A induce insulin resistance in human adipocytes and affects the secretion of adiponectin in an effect attributed to the increase in ROS production by defective mitochondria (Wang et al., 2013).”
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- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Induced mitochondrial dysfunction affects adiponectin secretion in human adipocytes, an effect attributed to increased ROS production by defective mitochondria.
“Further, induction of mitochondrial dysfunction by blocking respiration or knocking down the mitochondrial transcription factor A induce insulin resistance in human adipocytes and affects the secretion of adiponectin in an effect attributed to the increase in ROS production by defective mitochondria (Wang et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wang et al., 2013 source
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- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Mitochondrial dysfunctions in diet-induced obesity are modulated by caloric restriction and exercise.
“These dysfunctions have been modulated by CR and exercise (Putti et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Putti et al., 2015 source
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- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
MOTS-C appears mainly in skeletal muscle.
“The short open reading frame found within the mitochondrial 12S rRNA known as MOTS-C (mitochondrial open reading frame of the 12S rRNA-c) appears mainly in skeletal muscle and activate AMPK (Lee et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lee et al., 2016 source
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- Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
FoxO are involved in the induction of several stress response genes.
“FoxO are involved in the induction of several stress response genes”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Goto and Takano, 2009
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- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
Humanin has demonstrated protective capacity in age-related diseases such as T2DM and Alzheimer's disease.
“Humanin has demonstrated protective capacity in age-related diseases such as T2DM and Alzheimer's disease (Mahboobi et al., 2014) and is able to restore mitochondrial function after oxidative injury in retinal pigment epithelial cells (Sreekumar et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mahboobi et al., 2014 source
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- Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
Regulation of FoxO proteins during ageing and their modulation by mTOR, AMPK and sirtuins have associated these proteins with the protective effect of calorie restriction, polyphenols or exercise against mitochondrial damage by regulating autophagy and antioxidant protection, preventing progression of ageing-related disease.
“the regulation of FoxO proteins during ageing and their modulation by metabolic regulators such as mTOR, AMPK and sirtuins have associated these proteins with the protective effect of CR, polyphenols or exercise against mitochondrial damage by regulating autophagy and antioxidant protection preventing by these mechanisms the progression of ageing-related disease”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lopez-Lluch and Navas, 2016
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- Interpretationcitation§ Mitochondrial turnover can be regulated by different factors during ageing.
Mitochondria play an important role in the control of fat metabolism.
“Interestingly, treatment with MOTS-C in mice prevent agedependent and high-fat diet induced insulin resistance and obesity indicating an important role of mitochondria in the control of fat metabolism probably producing prolongevity effects (Fuku et al., 2015; Lee et al., 2015).”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Inactivation of sestrins in invertebrates results in metabolic pathologies including oxidative damage, mitochondrial dysfunction and fat accumulation.
“Research performed in invertebrates demonstrate that the inactivation of sestrins results in metabolic pathologies that include oxidative damage, mitochondrial dysfunction and fat accumulation (Lee et al., 2013b).”
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- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
The increase in fat mass is one of the major determinants of insulin resistance.
“The increase in fat mass is one of the major determinants of insulin resistance (Larson-Meyer et al., 2006).”
- Also stated in: § Metabolic syndrome, fat accumulation and mitochondria. · plain
“The increase in fat mass is one of the major determinants of insulin resistance (Larson-Meyer et al., 2006).”
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- Also stated in: § Metabolic syndrome, fat accumulation and mitochondria. · plain
- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
The protective effect of sestrins is probably mediated by eliminating damaged mitochondria, as in rat kidney cells.
“In agreement with this hypothesis, it has been recently demonstrated that the protective effect of sestrins depends on the promotion of autophagic degradation of Keaps 1 and Nrf2 activation by inhibition of mTORC1 (Rhee and Bae, 2015) probably by eliminating damaged mitochondria as in the case of rat kidney cells (Ishihara et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ishihara et al., 2013 source
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- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Resveratrol blocks LXRα-mediated hepatic lipogenesis by inducing Sesn2 gene.
“Resveratrol (RSV), a polyphenol that prevents lipid accumulation in liver, blocks Liver X receptor (LXRα)-mediated hepatic lipogenesis by inducing Sens2 gene (Jin et al., 2013), indicating a putative role of this family of proteins in fat accumulation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Jin et al., 2013 source
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- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
Treatment with MOTS-C in mice prevents age-dependent and high-fat diet-induced insulin resistance and obesity.
“Interestingly, treatment with MOTS-C in mice prevent agedependent and high-fat diet induced insulin resistance and obesity indicating an important role of mitochondria in the control of fat metabolism probably producing prolongevity effects (Fuku et al., 2015; Lee et al., 2015).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Sestrins could be considered key factors in the control of mitochondrial homeostasis in ageing and obesity and probably T2DM.
“All these evidences suggest that sestrins could be considered key factors in the control of mitochondrial homeostasis in ageing and obesity and probably T2DM.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings from animal models (mice, rats, worms) about mitochondrial function and fat metabolism can be extrapolated to humans.
- Interpretationcitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
There is a downregulation of fusion in mitochondria in obesity-related diseases.
“All these reports indicate that there is a downregulation of fusion in mitochondria in obesity related diseases.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
During ageing, the mitochondrial network tends to increase by inducing fusion, probably to maintain mitochondrial capacity.
“This response is opposite to the behaviour found during ageing in which mitochondrial network tends to increase by inducing fusion in a response that probably is triggered to maintain the capacity of mitochondria (Fig. 2).”
Quote in the paperSubstantial claim - Interpretationcitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Sestrins have a putative role in fat accumulation.
“Resveratrol (RSV), a polyphenol that prevents lipid accumulation in liver, blocks Liver X receptor (LXRα)-mediated hepatic lipogenesis by inducing Sens2 gene (Jin et al., 2013), indicating a putative role of this family of proteins in fat accumulation.”
- Also stated in: § Mitochondrial dysfunction is associated with age-dependent fat accumulation. · hedged
“Therefore, the Sens2-dependent repression of LXRα induced by RSV would indicate a key role of these proteins in fat accumulation during ageing.”
Quote in the paperSubstantial claim - Also stated in: § Mitochondrial dysfunction is associated with age-dependent fat accumulation. · hedged
- Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
When fat accumulates, mitochondrial activity can decrease by increasing fission processes and accumulating low-potential small mitochondria.
“When fat accumulates, mitochondrial activity can decrease by increasing fission processes and accumulating then, low potential small mitochondria.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Impaired mitochondrial function and dynamics are associated with diet-induced obesity, mainly affecting liver and skeletal muscle.
“Impaired mitochondrial function and dynamics have been associated with diet induced obesity mainly affecting liver and skeletal muscle (Putti et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Putti et al., 2015 source
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- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Mitochondrial dysfunction has been described in muscle, liver and adipose tissue during ageing and metabolic syndrome.
“Thus, mitochondrial dysfunction has been described in the main organs involved in the development of metabolic syndrome during ageing such as muscle, liver and adipose tissue (Patti and Corvera, 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Patti and Corvera, 2010 source
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- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
The protective effect of sestrins depends on promotion of autophagic degradation of Keaps1 and Nrf2 activation by inhibition of mTORC1.
“In agreement with this hypothesis, it has been recently demonstrated that the protective effect of sestrins depends on the promotion of autophagic degradation of Keaps 1 and Nrf2 activation by inhibition of mTORC1 (Rhee and Bae, 2015) probably by eliminating damaged mitochondria as in the case of rat kidney cells (Ishihara et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Rhee and Bae, 2015
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- Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
The same mechanism (sestrin-dependent autophagy/mTORC1 inhibition) is associated with the protective effect of sestrin2 in rodent dopaminergic neurons against rotenone toxicity.
“The same mechanism has been associated with the protective effect of sestrin2 in rodent dopaminergic neurons against rotenone toxicity (Hou et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hou et al., 2015 source
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- Premisenone given§ Regulation of AMPK and mTOR controls energy metabolism.
Regulation of FoxO proteins plays an essential role in mito- and autophagy.
“The regulation of Forkhead box proteins (FoxO) plays an essential role in mito- and autophagy.”
Quote in the paperNot a substantial claim - Interpretationcitation§ Metabolic syndrome, fat accumulation and mitochondria.
Modification of levels or activity of AMPK could explain the deterioration of adipose tissue physiology during ageing.
“Taken into consideration the central role of AMPK in the control of metabolism and mitochondria (Burkewitz et al., 2014), modification of levels or activity of AMPK could explain the deterioration of adipose tissue physiology during ageing.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Burkewitz et al., 2014 source
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- Premisecitation§ Inflammation and lipid accumulation.
Mitochondria is a central regulator of NLRP3 inflammasome activation through ROS, Ca2+, decrease of NAD+, Mfn or mitochondrial DNA.
“In fact, mitochondria is considered a central regulator of NLRP3 inflammasome activation through ROS, Ca 2+ , decrease of NAD + , Mfn or mitochondrial DNA (Gurung et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gurung et al., 2015 source
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- Interpretationcitation§ Metabolic syndrome, fat accumulation and mitochondria.
AMPK seems to be a key component in the progression of metabolic syndrome and insulin resistance in WAT.
“Among the regulators of metabolism, AMPK seems to be the key component in the progression of metabolic syndrome and insulin resistance in WAT.”
Quote in the paperSubstantial claim - Premisecitation§ Inflammation and lipid accumulation.
Inflammasome activation in fat tissues triggers fat cell senescence, connected with SASP.
“Furthermore, the inflammasome activation in fat tissues will trigger fat cell senescence, a phenomenon connected with the senescenceassociated secretory phenotype (SASP) (Newsholme and de Bittencourt, 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Newsholme and de Bittencourt, 2014
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- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Alterations in mitochondrial dynamics, particularly in Mfn2, are associated with reduced mitochondrial function in skeletal muscle in obesity and T2DM.
“Further, alterations in mitochondrial dynamics and in particular in Mfn2, have been associated with a reduced mitochondrial function in skeletal muscle in obesity and T2DM (Zorzano et al., 2009) and recently aberrant mitochondrial fission has been also associated with insulin resistance in mouse skeletal muscle (Jheng et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zorzano et al., 2009 source
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- Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?
The accumulation of fat during ageing is associated with higher levels of follicle-stimulating hormone (FSH) in both men and women.
“Another interesting paper has associated the accumulation of fat during ageing with higher levels of follicle-stimulating hormone (FSH) in both men and women (Liu et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Liu et al., 2015 source
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- Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In humans, fat deposits depend on gender.
“In humans, fat deposits depend on the gender of the individual (Palmer and Clegg, 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Palmer and Clegg, 2015 source
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- Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In men, the decrease in testosterone levels can be responsible for the increase of adiposity and fat accumulation in non-adipose tissue during ageing.
“In men, the decrease in testosterone levels can be responsible of the increase of adiposity and fat accumulation in non-adipose tissue during ageing (Mudali and Dobs, 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mudali and Dobs, 2004
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- Premisecitation§ Inflammation and lipid accumulation.
Chronically overactive inflammasome activity and production of IL-1β is associated with abnormal lipid accumulation in old rat liver resulting in steatohepatitis.
“Moreover, chronically overactive inflammasome activity and production of IL-1β has been associated with the abnormal lipid accumulation in old rat liver resulting in steatohepatitis (Chung et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chung et al., 2015 source
Not checked in the free run.
- Premisecitation§ Inflammation and lipid accumulation.
The release of danger signals from mitochondria promotes the formation of inflammasomes.
“The release of danger signals from mitochondria promotes the formation of inflammasomes. In fact, mitochondria is considered a central regulator of NLRP3 inflammasome activation through ROS, Ca 2+ , decrease of NAD + , Mfn or mitochondrial DNA (Gurung et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gurung et al., 2015 source
Not checked in the free run.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Aberrant mitochondrial fission is associated with insulin resistance in mouse skeletal muscle.
“Further, alterations in mitochondrial dynamics and in particular in Mfn2, have been associated with a reduced mitochondrial function in skeletal muscle in obesity and T2DM (Zorzano et al., 2009) and recently aberrant mitochondrial fission has been also associated with insulin resistance in mouse skeletal muscle (Jheng et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jheng et al., 2012 source
Not checked in the free run.
- Interpretationreasoning§ Metabolic syndrome, fat accumulation and mitochondria.
The role of mitochondria in muscle in high-fat diet-induced T2DM is not completely clear.
“These discrepancies indicate that the role of mitochondria in muscle in high-fat diet induced T2DM is not completely clear.”
Quote in the paperSubstantial claim - Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
In both rodents and humans, skeletal muscle from high-fat fed conditions shows higher H2O2-mitochondrial production affecting redox state without changes in mitochondrial respiratory function.
“In fact, it has been shown that, in both, rodents and humans, skeletal muscle from high-fat fed conditions show higher H2O2-mitochondrial production affecting the redox state of the cells but without changes in the mitochondrial respiratory function (Anderson et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Anderson et al., 2009 source
Not checked in the free run.
- Interpretationreasoning§ Inflammation and lipid accumulation.
The proinflammatory status that accompanies obesity is an important factor in fat accumulation during ageing.
“Another important fact to be taken into consideration in the accumulation of fat during ageing is the proinflammatory status that accompanies obesity.”
Quote in the paperNot a substantial claim - Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Deficiency in mitochondrial activity in muscle is associated with obesity and T2DM.
“On the other hand, deficiency in mitochondrial activity in muscle is associated with obesity and T2DM.”
- Also stated in: § Metabolic syndrome, fat accumulation and mitochondria. · plain
“deficiency in mitochondrial activity in muscle is associated with obesity and T2DM.”
Quote in the paperSubstantial claim0 of 3 sources checked - Also stated in: § Metabolic syndrome, fat accumulation and mitochondria. · plain
- Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Testosterone therapy prevents the gain in visceral fat in non-obese ageing men.
“In a similar response that women, testosterone therapy prevents the gain in visceral fat in non-obese ageing men (Allan et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Allan et al., 2008 source
Not checked in the free run.
- Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
NLRP3 inflammasome activation is associated with the evolution of hepatosteatosis, obesity and T2DM.
“and the evolution of hepatosteatosis, obesity and T2DM.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
NLRP3 inflammasome activation is associated with cell senescence and SASP.
“This activation is associated with cell senescence and SASP”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
Depletion of Mfn2 in anorexigenic POMC neurons causes severe obesity and leptin resistance, probably by affecting ER-stress.
“However, the depletion of Mfn2 in the anorexigenic POMC neurons causes severe obesity and leptin resistance probably by affecting ER-stress (Schneeberger et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Schneeberger et al., 2013 source
Not checked in the free run.
- Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In rat models, the expression of prohibitins responds to the levels of oestrogens in WAT.
“Further, in rat models, the expression of prohibitins responds to the levels of oestrogens in WAT. The level of prohibitins were stimulated by estradiol in WAT and liver in both, controls and high-fat fed rats (Choi et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Choi et al., 2015 source
Not checked in the free run.
- Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
Inhibition of mTOR in POMC neurons causes reduction of food intake and weight loss in old mice.
“On the contrary, the inhibition of mTOR in these neurons caused reduction of food intake and weight loss in old mice indicating the importance of this regulator in satiety control (Yang et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Yang et al., 2012 source
Not checked in the free run.
- Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
Age-dependent oestrogen decay produces mitochondrial dysfunction.
“This will produce mitochondrial dysfunction.”
Quote in the paperSubstantial claim - Premisenone given§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
Both obesity and ageing are associated with rewiring of a principal brain pathway modulating energy homeostasis through promoting reduced activity of satiety POMC neurons.
“Both obesity and ageing are associated with rewiring of a principal brain pathway modulating energy homeostasis through promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Figure legends.
These events produce an increase of reactive oxygen species.
“These events produce the reduction of respiration, membrane potential and the increase of reactive oxygen species.”
Quote in the paperNot a substantial claim - Premisenone given§ Abstract
The recent literature demonstrates a complex interaction between nutritional sensors and mitochondrial homeostasis in adipose tissue physiology and in fat accumulation in muscle and liver.
“The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Figure legends.
The imbalance in mitochondrial homeostasis causes accumulation of damaged mitochondria (giant or small and damaged).
“causing the accumulation of damaged mitochondria as giant or small and damaged mitochondria.”
Quote in the paperNot a substantial claim - Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
In mice, mitochondrial fusion increases in orexigenic NPY/Agrp neurons, inducing neuronal activity that controls storage of excess energy in fat when mice are fed a high-fat diet.
“In studies performed in mice it has been demonstrated that mitochondrial fusion increases in orexigenic NPY/Agrp neurons inducing neuronal activity that control the storage of excess of energy in fat when mice are fed with high-fat diet (Dietrich et al., 2013).”
- Also stated in: § Mitochondrial function in POMC neurons and its effect on the control of satiety. · boosted
“In studies performed in mice it has been demonstrated that mitochondrial fusion increases in orexigenic NPY/Agrp neurons inducing neuronal activity that control the storage of excess of energy in fat when mice are fed with high-fat diet (Dietrich et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dietrich et al., 2013 source
Not checked in the free run.
- Also stated in: § Mitochondrial function in POMC neurons and its effect on the control of satiety. · boosted
- Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
Visceral fat accumulation contributes to higher mitochondrial dysfunction by inhibiting mito- and autophagy through mTORC1 activity.
“will contribute to higher mitochondrial dysfunction by inhibiting mito- and autophagy through mTORC1 activity”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Figure legends.
These events produce a reduction of respiration.
“These events produce the reduction of respiration, membrane potential and the increase of reactive oxygen species.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Concluding remarks.
In a vicious cycle, insulin resistance and proinflammatory cytokines promote more damage in mitochondria.
“In a vicious cycle, insulin resistance and proinflammatory cytokines promote more damage in mitochondria.”
- Also stated in: § Concluding remarks. · plain
“In a vicious cycle, insulin resistance and proinflammatory cytokines promote more damage in mitochondria.”
Quote in the paperSubstantial claim - Also stated in: § Concluding remarks. · plain
- Interpretationreasoning§ Figure legends.
AMPK/SIRT induce mitochondrial biogenesis through PGC1α and mitophagy.
“induce mitochondrial biogenesis through PGC1α and mitophagy”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Figure legends.
Prolongevity factors prevent fat accumulation.
“preventing then fat accumulation.”
Quote in the paperSubstantial claim - Interpretationnone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
The increase of FSH found in aged individuals contributes to the accumulation of visceral fat.
“the increase of FSH found in aged individuals will contribute to the accumulation of visceral fat”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
A dysfunction in these factors can cause the accumulation of giant mitochondria in ageing.
“A dysfunction in these factors can cause the accumulation of giant mitochondria in ageing”
Quote in the paperNot a substantial claim - Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In MCF-7 cells, estradiol treatment induces mitochondrial biogenesis.
“In these cells, estradiol treatment also induced mitochondrial biogenesis (Sastre-Serra et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sastre-Serra et al., 2012 source
Not checked in the free run.
- Interpretationnone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
Prolongevity interventions such as calorie restriction, exercise and diet rich in nutraceuticals prevent mitochondrial decay.
“prolongevity interventions such as calorie restriction, exercise and diet rich in nutraceuticals prevent mitochondrial decay”
Quote in the paperNot a substantial claim - Premisenone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
Balanced mitochondrial activity maintains a control of mitochondrial population by fusion/fission balance.
“Balanced mitochondrial activity maintains a control of mitochondrial population by fusion/fission balance”
Quote in the paperSubstantial claim - Interpretationnone given§ Figure legends.
Ageing produces an imbalance in mitochondrial homeostasis.
“Ageing and the decay of oestrogens produce an unbalance in mitochondrial homeostasis”
Quote in the paperSubstantial claim - Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
Mitochondrial dysfunction produces NLRP3 inflammasome activation by increasing ROS that acts as Damage-activating molecular pattern.
“Mitochondrial dysfunction produces NLRP3 inflammasome activation by increasing ROS that acts as Damage-activating molecular pattern.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Figure legends.
These events produce a reduction of membrane potential.
“These events produce the reduction of respiration, membrane potential and the increase of reactive oxygen species.”
Quote in the paperSubstantial claim - Premisenone given§ References.
Mitochondrial dysfunction is associated with age-related fat accumulation.
“Mitochondrial dysfunction is associated with age.-related fat accumulation.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.
Mitochondrial dysfunction is at the centre of the regulation of fat metabolism during ageing.
“Mitochondrial dysfunction is at the centre of the regulation of fat metabolism during ageing.”
Quote in the paperSubstantial claim - Interpretationnone given§ Concluding remarks.
Many evidences indicate that mitochondrial dysfunction is associated with the development of obesity and the appearance and progression of age-related diseases.
“Many evidences indicate that mitochondrial dysfunction is associated with the development of obesity and the appearance and progression of age-related diseases (Fig.5).”
Quote in the paperNot a substantial claim- Rests on an assumption: Mitochondrial dysfunction is a cause, not merely a consequence, of fat accumulation and insulin resistance.
- Premisenone given§ Abstract
These nutritional sensors control mitochondrial biogenesis, dynamics, and turnover through mito- and autophagy.
“These nutritional sensors control mitochondrial biogenesis, dynamics, by regulating fusion and fission processes, and turnover through mito- and autophagy.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
Mitochondrial dynamics in NPY/Agrp and POMC neurons play an important role in the regulation of energy balance and in diet- and age-related obesity.
“These and other results suggest that mitochondrial dynamics in NPY/Agrp and POMC neurons also play an important role in the regulation of the energy balance and in diet and agerelated obesity.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
The activity of NPY/Agrp neurons is impaired when mitochondrial fusion mechanism is altered, producing resistance to fat gain during high-fat diet.
“The activity of these neurons is impaired when the mitochondrial fusion mechanism is altered producing resistance to fat gain during high fat diet (Dietrich et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dietrich et al., 2013 source
Not checked in the free run.
- Premisenone given§ Abstract
Dysfunction of mitochondria has been associated with ageing and age-related diseases.
“Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
Mitochondrial dysfunction is associated with functional decline in tissues and organs during ageing.
“Mitochondrial dysfunction is associated with the functional decline found in tissues and organs during ageing (Riera et al., 2016)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Riera et al., 2016 source
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- Premisenone given§ Molecular mechanisms involved in the regulation of mitochondrial physiology.
Mitochondrial physiology, dynamics and turnover respond to the relationship between activities of key regulators of cell metabolism.
“Mitochondrial physiology, dynamics and turnover respond to the relationship between the activities of key regulators of cell metabolism.”
Quote in the paperNot a substantial claim - Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.
Sirtuins act as metabolic sensors by detecting fluctuations in NAD+/NADH ratio.
“Sirtuins also act as metabolic sensors by detecting fluctuations in the NAD + /NADH ratio in cells.”
Quote in the paperNot a substantial claim - Premisecitation§ Introduction
Mitochondrial dysfunction has been associated with age-related diseases such as neurological disorders, cardiovascular disease, liver and kidney diseases, diabetes and cancer.
“it has been associated with a number of age-related diseases such as neurological disorders, cardiovascularCVD, liver and kidney diseases, diabetes and cancer (Lane et al., 2015; Payne and Chinnery, 2015; Ryan et al., 2015; Wallace, 2012).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
AMPK inhibits transcriptional activity of SREBP, decreasing expression of genes involved in fatty acid synthesis.
“AMPK also inhibits the transcriptional activity of sterol regulatory element binding protein (SREBP) decreasing the expression of genes involved in fatty acid synthesis (Li et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Li et al., 2011
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- Premisecitation§ Introduction
Dedifferentiation of these adipose-like cells occurs by decrease of adipogenic factors C/EBPalpha and PPAR-gamma.
“Their dedifferentiation occurs by the decrease of adipogenic factors such as CCAAT/enhancer binding alpha (C/EBPalpha) and peroxisome proliferator activated receptor gamma (PPAR -γ ), a known mitochondrial regulator (Kirkland et al., 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kirkland et al., 2002 source
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- Premisenone given§ Regulation of AMPK and mTOR controls energy metabolism.
Control of mitochondrial biogenesis and turnover through AMPK and mTOR activities is key in regulation of cell metabolism and mitochondria.
“The cControl of mitochondrial biogenesis and turnover through AMPK and mTOR activities is key in the regulation cell metabolism and, in particular, mitochondria.”
Quote in the paperNot a substantial claim - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
In human muscle, ageing is accompanied by a higher need of mitochondria to maintain the same respiratory capacity as in young people, indicating decay in mitochondrial efficiency.
“In human muscle, ageing is accompanied by a higher need of mitochondria to maintain the same respiratory capacity as in young people indicating decay in mitochondrial efficiency (Larsen et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Larsen et al., 2012 source
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- Premisenone given§ Mitochondrial activity and turnover are affected during ageing.
The bioenergetic state of the cell is directly related with the regulation of mitochondrial dynamics.
“The bioenergetic state of the cell is directly related with the regulation of mitochondrial dynamics, ; the balance in fusion/fission processes occurring in the mitochondrial network.”
Quote in the paperNot a substantial claim- Rests on an assumption: The bioenergetic state of the cell is directly related with the regulation of mitochondrial dynamics.
- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Ageing is associated with accumulation of deficient mitochondria that produce a significant increase of ROS generation.
“Some evidence indicate that ageing is associated with the accumulation of deficient mitochondria that produce a significant increase of ROS generation (Chistiakov et al., 2014; Merry, 2002).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
A moderate level of ROS production during life can be beneficial by inducing hormetic responses that reinforce the capacity of the organism to respond to stronger injury.
“a moderate level of ROS production during life can be beneficial by inducing hormetic responses that reinforce the capacity of the organism to respond to stronger injury (Rattan, 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Rattan, 2008 source
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- Interpretationreasoning§ Mitochondrial activity and turnover are affected during ageing.
Control of the accumulation of damaged mitochondria is an important factor in the progression of ageing.
“indicating that the control of the accumulation of damaged mitochondria is an important factor in the progression of ageing.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Correct activity of the quality control of mitochondria is considered a crucial factor in counteracting the ageing process.
“The correct activity of the quality control of mitochondria is considered a crucial factor in counteracting ageing process (Weber and Reichert, 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Weber and Reichert, 2010
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Prolongevity factors such as CR, exercise and polyphenols prevent the accumulation of damaged mitochondria at least in part by inducing mito- and autophagy.
“prolongevity factors such as CR, exercise and polyphenols prevent the accumulation of damaged mitochondria at least in part by inducing mito- and autophagy (Lopez-Lluch and Navas, 2015) (LopezLluch and Navas, 2016)”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Lopez-Lluch and Navas, 2015
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- cites LopezLluch and Navas, 2016
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
In Drosophila, ROS increase with age as mitochondrial function deteriorates.
“a recent study in Drosophila indicates that ROS increase with age as mitochondrial function deteriorates”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Scialo et al., 2016 source
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Mitochondria play a key role in pathophysiology of ageing and in earlier stages of events leading to ageing phenotype.
“Mitochondria play a key role in the pathophysiology of ageing and in earlier stages of the events leading to the ageing phenotype (Gonzalez-Freire et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gonzalez-Freire et al., 2015 source
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
High levels of ROS during the life of an organism act as secondary messengers inducing endogenous protective mechanisms that can increase lifespan in animals.
“high levels of ROS during the life of the organism seems to act as secondary messengers inducing endogenous protective mechanisms in the animals that can increase lifespan (Scialo et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Scialo et al., 2016 source
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- Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
Regulation of FoxO proteins during ageing and their modulation by mTOR, AMPK and sirtuins have associated these proteins with protective effect of calorie restriction, polyphenols or exercise against mitochondrial damage through regulating autophagy and antioxidant protection.
“the regulation of FoxO proteins during ageing and their modulation by metabolic regulators such as mTOR, AMPK and sirtuins have associated these proteins with the protective effect of CR, polyphenols or exercise against mitochondrial damage through by regulating autophagy and antioxidant protection preventing by these mechanisms the progression of ageing-related disease (Lopez-Lluch and Navas, 201”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Lopez-Lluch and Navas, 2015
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- cites Lopez-Lluch and Navas, 2016
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Assembly of mitochondrial electron transport chain complexes in supercomplexes seems to regulate ROS production.
“the assembly of these complexes in supercomplexes seems to regulate ROS production (Goncalves et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Goncalves et al., 2015 source
Not checked in the free run.
- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Near all complexes of the mitochondrial electron transport chain are involved in ROS production.
“Near all the complexes of the mitochondrial electron transport chain are involved in ROS production”
Quote in the paperSubstantial claim - Premisereasoning§ Mitochondrial activity and turnover are affected during ageing.
If ROS production is balanced with antioxidant enzymes, oxidative damage does not occur.
“If ROS production is balanced with antioxidant enzymes, oxidative damage did not occur”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Mitochondrial activity and turnover are affected during ageing.
Maintenance of mitochondrial turnover removing ROS-producing damaged mitochondria at the same time as biogenesis produces new components is essential in the prolongevity effects of CR, exercise and polyphenols.
“Thus, it seems clear that maintenance of mitochondrial turnover removing ROS-producing damaged mitochondria at the same time that biogenesis produces new components is essential in the prolongevity effects of these factors.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Renovation of the mitochondrial network plays a key role in health-span increase after CR.
“rRenovation of the mitochondrial network plays a key role in health-span increase after CR (Lopez-Lluch et al., 2008)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lopez-Lluch et al., 2008 source
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- Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.
FoxO are involved in induction of several stress response genes.
“FoxO are involved in the induction of several stress response genes (Goto and Takano, 2009)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Goto and Takano, 2009
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Fission segregates components of the mitochondrial network that are irreversibly damaged or unnecessary for subsequent removal.
“Fission segregates components of the network that are irreversibly damaged or unnecessary for subsequent removal (Twig et al., 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Twig et al., 2008 source
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Impairment of mitochondrial biogenesis is a factor involved in the decay in mitochondrial turnover during ageing, especially in high energy demanding tissues such as muscle, brain or heart.
“Another factor involved in the decay in mitochondrial turnover during ageing is the impairment of mitochondrial biogenesis, especially in high energy demanding tissues such as muscle, brain or heart (Conley et al., 2000; Short et al., 2005).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Accumulation of damaged mitochondria during ageing is associated with decline of mitochondrial turnover through inhibiting mitophagy.
“Accumulation of damaged mitochondria during ageing is also associated with the decline of the mitochondrial turnover through inhibiting mitophagy; a specific autophagy process that removes damaged mitochondria (Chistiakov et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Chistiakov et al., 2014 source
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Progressive deterioration of supercomplexes during ageing could be the cause of an irreversible increase in ROS during ageing in older organisms.
“a progressive deterioration of supercomplexes in during ageing could be the cause of an irreversible increase in ROS during ageingin older organisms (Genova and Lenaz, 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Genova and Lenaz, 2015
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
If antioxidant enzymes decay during aging, oxidative damage accumulates.
“if these enzymes decay during aging, as has been found in different models (Rodriguez-Bies et al., 2015; Rodriguez-Bies et al., 2016; Tung et al., 2014; Tung et al., 2015b), oxidative damage accumulates.”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Ageing delaying interventions such as CR, exercise or nutraceuticals as resveratrol induce mitochondrial biogenesis in humans and other organisms.
“ageing delaying interventions such as CR, exercise or nutraceuticals as resveratrol also induce mitochondrial biogenesis in humans and other organisms (Baur et al., 2010; Feige et al., 2008; Rodriguez-Bies et al., 2015).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Senescence has been associated with the accumulation of giant dysfunctional mitochondria characterized by highly interconnected networks and ultrastructural abnormalities in human lymphocytes and mice cells.
“senescence has been associated with the accumulation of giant dysfunctional mitochondria characterized by highly interconnected networks and ultrastructural abnormalities in human lymphocytes and mice cells (Beregi and Regius, 1987)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Beregi and Regius, 1987
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Placenta, skeletal muscle, vascular smooth cells and neurons suffer mitochondrial defects by deficiencies in mitochondrial dynamics.
“Placenta, skeletal muscle, vascular smooth cells and neurons suffer mitochondrial defects by deficiencies in mitochondrial dynamics (Chen and Chan, 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chen and Chan, 2005
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
In a Drosophila model of longevity, moderate levels of ROS can induce prolongevity effects by activating recycling mechanisms such as mitophagy and autophagy.
“in a model of longevity in Drosophila it has been recently demonstrated that moderated levels of ROS can induce prolongevity effects (Scialo et al., 2016) by activating recycling mechanisms such as mitophagy and autophagy (Weber and Reichert, 2010).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Scialo et al., 2016 source
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- cites Weber and Reichert, 2010
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Defects in mitochondrial fusion/fission dynamics are essential for the quality control of mitochondria in neurodegeneration and hypothalamic dysfunction.
“or in neurodegeneration and hypothalamic dysfunction (Zorzano and Claret, 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zorzano and Claret, 2015
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
RNAi studies have demonstrated an inverse relationship between fusion capacity and respiration rates mainly affecting complexes I, III and IV in mammals and humans.
“RNAi studies have demonstrated an inverse relationship between fusion capacity and respiration rates mainly affecting complexes I, III and IV in mammals and humans (Chen et al., 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chen et al., 2005
Not checked in the free run.
- Interpretationcitation§ Mitochondrial activity and turnover are affected during ageing.
A functional fission machinery is important to discard damaged mitochondria by autophagy or mitophagy.
“These facts highlight the importance of a functional fission machinery to discard damaged mitochondria by autophagy or mitophagy (Gomes and Scorrano, 2008; Twig et al., 2008).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Gomes and Scorrano, 2008
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- cites Twig et al., 2008 source
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- Interpretationnone given§ Mitochondrial turnover can be regulated by different factors during ageing.
Control of mitochondrial dynamics including turnover plays an essential role in ageing.
“Control of mitochondrial dynamics including turnover seems to play an essential role in ageing.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Blocking the fission process by depleting FIS1 or blocking DRP1 activity leads to cell senescence in human cells accompanied by the accumulation of damaged mitochondria showing lower mitochondrial potential and higher ROS production.
“Blocking the fission process by depleting FIS1 or blocking DRP1 activity leads to cell senescence in human cells accompanied by the accumulation of damaged mitochondria showing lower mitochondrial potential and higher ROS production (Lee et al., 2007; Park et al., 2010).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Mutations in FIS1 disrupt downstream mitochondrial degradation events, indicating the importance of this protein in mitochondrial turnover.
“although mutations in FIS1 disrupt downstream mitochondrial degradation events indicating the importance of this protein in mitochondrial turnover (Shen et al., 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shen et al., 2014 source
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
A decrease in the levels of mitochondrial fission proteins can be a defensive response to maintain functional cell mitochondria.
“or even a defensive response to maintain functional cell mitochondria (Chen and Chan, 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chen and Chan, 2005
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- Interpretationreasoning§ Mitochondrial activity and turnover are affected during ageing.
Dysfunction in the control of mitochondrial dynamics can be associated with the accumulation of damaged mitochondria during ageing in different organs including adipose tissue.
“All these evidence found in mammals models and humans indicate that dysfunction in the control of mitochondrial dynamics can be associated with the accumulation of damaged mitochondria during ageing in different organs including adipose tissue.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
Defects in mitochondrial fusion/fission dynamics are essential for the quality control of mitochondria in many age-related diseases, as in cardiac homeostasis and senescence.
“In other organs, defects in mitochondrial fusion/fission dynamics are also essential for the quality control of mitochondria in many age-related diseases as in the case of cardiac homeostasis and senescence (Biala et al., 2015)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Biala et al., 2015 source
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- Premisecitation§ Mitochondrial activity and turnover are affected during ageing.
AMPK-dependent modulation of FoxO-dependent autophagy and PGC1α-regulated mitochondrial biogenesis are involved in ROS-dependent mechanisms increasing mitochondrial metabolism.
“it seems that the AMPK-dependent modulation of FoxO-dependent autophagy and PGC1α-regulated mitochondrial biogenesis are involved (Li et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Li et al., 2015
Not checked in the free run.
- Interpretationreasoning§ Mitochondrial activity and turnover are affected during ageing.
The balance between ROS production and the capacity of cells to respond to ROS levels could affect cell homeostasis during ageing.
“This means that the balance between ROS production and the capacity of the cells to respond to ROS levels could affect cell homeostasis during ageing.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.
Sestrins regulate mTORC1 activity by binding AMPK, activating it and repressing mTORC1 activity.
“Sestrins are able to bind AMPK activating it and, by this mechanism, repress mTORC1 activity (Budanov and Karin, 2008).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Budanov and Karin, 2008 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans.
“conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans (Cartoni et al., 2005; Dolinsky et al., 2013; Soriano et al., 2006).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
A screen of differentially expressed genes from skeletal muscle of obese rats has identified Mfn2 as a suppressor of obesity.
“a screen of differentially expressed genes from skeletal muscle of obese rats has identified Mfn2 as a suppressor of obesity (Bach et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bach et al., 2003 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Overexpression of prohibitin in adipocytes produces development of obesity in mice accompanied by induction of mitochondrial biogenesis.
“overexpression of prohibitin in adipocytes produces the development of obesity in mice accompanied by the induction of mitochondrial biogenesis (Ande et al., 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ande et al., 2014 source
Not checked in the free run.
- Interpretationcitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
SIRT1 is needed for correct regulation of adipose tissue function.
“This indicates that SIRT1 is needed for a correct regulation of the adipose tissue function (Abdesselem et al., 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Abdesselem et al., 2016 source
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- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Rapamycin has been associated with prevention of age-related diseases and extension of lifespan in both obese and lean mice.
“rapamycin has been associated with the prevention of age-related diseases and the extension of lifespan in both, obese and lean mice (Liu et al., 2014)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Liu et al., 2014 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Metformin-dependent AMPK activation protects mitochondria in Huntington's disease by affecting mitochondrial dynamics.
“metformin-dependent AMPK activation has recently demonstrated protection of mitochondria in huntington's disease by affecting mitochondrial dynamics (Jin et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jin et al., 2016 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Transgenic mice deficient in Sens2 and Sens3 genes have demonstrated the important role of these proteins in the suppression of age and obesity-associated mitochondrial disorders.
“transgenic mice deficient in Sens2 and Sens3 genes have demonstrated the important role of these proteins in the suppression of age and obesity-associated mitochondrial disorders (Bae et al., 2013; Lee et al., 2012).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Lower levels of Mfn2 have been associated with fragmentation of the mitochondrial network and decrease of membrane potential in rat skeletal muscle.
“Lower levels of Mfn2 have been associated with the fragmentation of the mitochondrial network and the decrease of membrane potential in rat skeletal muscle (Pich et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Pich et al., 2005 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Higher mitochondrial fission has been associated with fat accumulation in genetically induced obesity (ob/ob) mice or in high-fat induced obesity.
“higher mitochondrial fission has been also associated with fat accumulation in genetically induced obesity (ob/ob) mice or in high-fat induced obesity (Jheng et al., 2012)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jheng et al., 2012 source
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- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Prolongevity CR mimetics such as rapamycin and metformin have been proposed to modulate mitochondrial dynamics in obesity and age-related diseases.
“Prolongevity CR mimetics such as rapamycin and metformin have also been proposed to modulate mitochondrial dynamics in obesity and age-related diseases (Mercken et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Mercken et al., 2012 source
Not checked in the free run.
- Premisenone given§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
In T2DM and obese people, abnormalities due to lower mitochondrial functionality have been shown.
“In T2DM and obese people abnormalities due to lower mitochondrial functionality have been shown.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Lower bioenergetics efficiency due to Mfn2 loss of function has been associated with development of obesity by reducing energy expenditure and increasing fat energy store in mammals and humans.
“This lower bioenergetics efficiency due to Mfn2 loss of function has been associated with the development of obesity by reducing energy expenditure and increasing fat energy store in mammals and humans (Liesa et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Liesa et al., 2009 source
Not checked in the free run.
- Interpretationnone given§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Mitochondrial dysfunction is associated with ageing progression.
“It seems clear that mitochondrial dysfunction is associated with ageing progression.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
In T2DM and obese people, a transient increase in oxidative capacity was found in human liver at the same time that oxidative stress increases.
“in these cases a transient increase in oxidative capacity was found in human liver at the same time that oxidative stress increases (Koliaki and Roden, 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Koliaki and Roden, 2016
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Impaired mitochondrial function and dynamics have been associated with diet induced obesity mainly affecting liver and skeletal muscle.
“Impaired mitochondrial function and dynamics have been associated with diet induced obesity mainly affecting liver and skeletal muscle (Putti et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Putti et al., 2015 source
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- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
A key role of SIRT1 in hyperplasia of adipocytes has been suggested.
“Very recently, a key role of SIRT1 in hyperplasia, the increase of cell number, of adipocytes, has been suggested.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Abdesselem et al., 2016 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Sestrins-dependent mTORC1 inactivation through AMPK induction is critical in the maintenance of autophagy and elimination of dysfunctional mitochondria.
“sestrins-dependent mTORC1 inactivation through AMPK induction is critical in the maintenance of autophagy and, then, the elimination of dysfunctional mitochondria (Ishihara et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ishihara et al., 2013 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Inactivation of PHB-2 in mice brain affects mitochondrial structure and activity resulting in neurodegeneration by hyperphosphorylation of Tau.
“inactivation of PHB-2 in mice brain affects mitochondrial structure and activity resulting in neurodegeneration by hyperphosphorylation of Tau (Merkwirth et al., 2012)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Merkwirth et al., 2012 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Reduced expression of Mfn2 has been found in skeletal muscle in both obese and T2DM patients.
“Reduced expression of Mfn2 has been found in skeletal muscle in both, obese and T2DM patients (Bach et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bach et al., 2005 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Inactivation of PHB-2 alters beta-cell function in pancreas producing diabetes.
“or alters beta-cell function in pancreas producing diabetes (Supale et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Supale et al., 2013 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Rapamycin reduces lifespan in obese db/db mice.
“a recent paper indicate that rapamycin reduces lifespan in the obese db/db mice (Sataranatarajan et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sataranatarajan et al., 2016 source
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- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Sens3 has been associated with activation of mTORC2 and Akt phosphorylation enhancing insulin sensitivity and glucose metabolism in mice.
“Sens3 has been recently associated with the activation of mTORC2 and Akt phosphorylation enhancing insulin sensitivity and glucose metabolism in mice (Tao et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tao et al., 2015 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Higher mitochondrial fission has been associated with insulin resistance in the same mice model.
“and with insulin resistance in the same mice model (Holmstrom et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Holmstrom et al., 2012 source
Not checked in the free run.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Pin1 rises in high fat state in mouse liver.
“prolyl isomerase, Pin1, has been shown to rise in high fat state in mouse liver (Nakatsu et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Nakatsu et al., 2011 source
Not checked in the free run.
- Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Sens2-dependent repression of LXRα induced by RSV indicates a key role of these proteins in fat accumulation during ageing.
“Therefore, the Sens2-dependent repression of LXRα induced by RSV would indicate a key role of these proteins in fat accumulation during ageing.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
This response is opposite to the behaviour found during ageing in which the mitochondrial network tends to increase by inducing fusion, probably to maintain the capacity of mitochondria.
“This response is opposite to the behaviour found during ageing in which mitochondrial network tends to increase by inducing fusion in a response that probably is triggered to maintain the capacity of mitochondria (Fig. 2).”
Quote in the paperSubstantial claim - Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Obesity is associated with impairment of the ability to transition between fatty acid and glucose metabolism.
“obesity is associated with the impairment of the ability to transit between fatty acid and glucose metabolism.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Griffin et al., 2015
Not checked in the free run.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
In both rodents and humans, skeletal muscle from high-fat fed conditions show higher H2O2-mitochondrial production affecting the redox state of the cells but without changes in mitochondrial respiratory function.
“in both, rodents and humans, skeletal muscle from high-fat fed conditions show higher H 2 O2-mitochondrial production affecting the redox state of the cells but without changes in the mitochondrial respiratory function (Anderson et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Anderson et al., 2009 source
Not checked in the free run.
- Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
When fat accumulates, mitochondrial activity can decrease by increasing fission processes and accumulating low potential small mitochondria.
“When fat accumulates, mitochondrial activity can decrease by increasing fission processes and accumulating then, low potential small mitochondria.”
Quote in the paperSubstantial claim - Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Metabolic inflexibility is present in obese people because they oxidize lipids in insulin-stimulated conditions instead of metabolizing glucose.
“that is present in obese people since they are able to oxidize lipids in insulin-stimulated conditions instead to metabolize glucose”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Storlien et al., 2004 source
Not checked in the free run.
- Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Inactivation of sestrins results in metabolic pathologies that include oxidative damage, mitochondrial dysfunction and fat accumulation.
“Research performed in invertebrates demonstrate that the inactivation of sestrins results in metabolic pathologies that include oxidative damage, mitochondrial dysfunction and fat accumulation (Lee et al., 2013b).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lee et al., 2013b
Not checked in the free run.
- Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Sestrins could be key factors in the control of mitochondrial homeostasis in ageing and obesity and probably T2DM.
“All these evidences suggest that sestrins could be considered key factors in the control of mitochondrial homeostasis in ageing and obesity and probably T2DM.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Sestrins expression decays during ageing.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Aberrant mitochondrial fission has been associated with insulin resistance in mouse skeletal muscle.
“aberrant mitochondrial fission has been also associated with insulin resistance in mouse skeletal muscle (Jheng et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jheng et al., 2012 source
Not checked in the free run.
- Interpretationreasoning§ Metabolic syndrome, fat accumulation and mitochondria.
These discrepancies indicate that the role of mitochondria in muscle in high-fat diet induced T2DM is not completely clear.
“These discrepancies indicate that the role of mitochondria in muscle in high-fat diet induced T2DM is not completely clear.”
Quote in the paperSubstantial claim - Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
Resveratrol blocks LXRα-mediated hepatic lipogenesis by inducing Sens2 gene.
“Resveratrol (RSV), a polyphenol that prevents lipid accumulation in liver, blocks Liver X receptor (LXRα)-mediated hepatic lipogenesis by inducing Sens2 gene (Jin et al., 2013)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Jin et al., 2013 source
Not checked in the free run.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Mitochondrial dysfunction has been described in the main organs involved in the development of metabolic syndrome during ageing such as muscle, liver and adipose tissue.
“mitochondrial dysfunction has been described in the main organs involved in the development of metabolic syndrome during ageing such as muscle, liver and adipose tissue (Patti and Corvera, 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Patti and Corvera, 2010 source
Not checked in the free run.
- Rests on an assumption: Obesity and T2DM are age-related diseases.
- Interpretationreasoning§ Metabolic syndrome, fat accumulation and mitochondria.
Modification of AMPK levels or activity could explain deterioration of adipose tissue physiology during ageing.
“modification of levels or activity of AMPK could explain the deterioration of adipose tissue physiology during ageing.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Burkewitz et al., 2014 source
Not checked in the free run.
- Rests on an assumption: AMPK is the key component in progression of metabolic syndrome and insulin resistance in WAT.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Exposure to prepregnancy maternal obesity impairs the activity of factors involved in mitochondrial dynamics in the offspring.
“exposure to prepregnancy maternal obesity impairs the activity of factors involved in mitochondrial dynamics in the offspring (Borengasser et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Borengasser et al., 2014 source
Not checked in the free run.
- Interpretationcitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.
There is a downregulation of fusion in mitochondria in obesity related diseases.
“All these reports indicate that there is a downregulation of fusion in mitochondria in obesity related diseases.”
Quote in the paperSubstantial claim - Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
In several models including rodents and humans, obesity and T2DM are associated with mitochondrial dysfunction indicated by low expression of mtDNA and reduction of levels of proteins involved in OXPHOS.
“In several of the models studied including rodents and humans, these diseases are associated with mitochondrial dysfunction indicated by low expression of mtDNA and reduction of the levels of proteins involved in oxidative phosphorylation (OXPHOS).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Patti and Corvera, 2010 source
Not checked in the free run.
- Rests on an assumption: Obesity and T2DM are age-related diseases.
- Interpretationreasoning§ Metabolic syndrome, fat accumulation and mitochondria.
Accumulation of damaged mitochondria would explain the increase of ROS in skeletal muscle associated with insulin resistance of obese individuals and the appearance of T2DM and muscle malfunction.
“The accumulation of damaged mitochondria would explain the increase of ROS in skeletal muscle associated with insulin resistance of obese individuals and the appearance of T2DM and muscle malfunction during”
Quote in the paperSubstantial claim - Premisecitation§ Inflammation and lipid accumulation.
Mitochondria are a central regulator of NLRP3 inflammasome activation through ROS, Ca2+, decrease of NAD+, Mfn or mitochondrial DNA.
“mitochondria is considered a central regulator of NLRP3 inflammasome activation through ROS, Ca 2+ , decrease of NAD + , Mfn or mitochondrial DNA (Gurung et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gurung et al., 2015 source
Not checked in the free run.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Mitochondria are the key organelles affecting metabolic inflexibility.
“being mitochondria the key organelles affecting this incapacity (Storlien et al., 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Storlien et al., 2004 source
Not checked in the free run.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Phosphorylated AMPK modulates many downstream substrates, resulting in increased lipid oxidation and glucose uptake.
“Phosphorylated AMPK modulates the activity of many downstream substrates resulting in the increase in lipid oxidation and the uptake of glucose (Jager et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Jager et al., 2007 source
Not checked in the free run.
- Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.
Alterations in mitochondrial dynamics and in particular in Mfn2 have been associated with reduced mitochondrial function in skeletal muscle in obesity and T2DM.
“alterations in mitochondrial dynamics and in particular in Mfn2, have been associated with a reduced mitochondrial function in skeletal muscle in obesity and T2DM (Zorzano et al., 2009)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Zorzano et al., 2009 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Hormone-responsive elements are also found in nuclear genes encoding mitochondrial transcription factors that modulate OXPHOS gene expression.
“tThese hormone-responsible elements are also found in nuclear gene encoding mitochondrial transcription factors that also modulate OXPHOS gene expression (Psarra et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Psarra et al., 2006 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Oestrogens and androgens can affect transcription of mitochondrial OXPHOS components.
“oestrogens and androgens can affect the transcription of mitochondria OXPHOS components (Scheller et al., 2003).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Scheller et al., 2003 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Differences in metabolism of visceral and subcutaneous fat have been related to higher risk of metabolic syndrome in men than women due to higher free fatty acid production in visceral fat than subcutaneous fat.
“The differences in the metabolism of visceral and subcutaneous fat has been related to a higher risk of metabolic syndrome in men than in women due to a higher free fatty acid production in visceral fat than in subcutaneous fat (Palmer and Clegg, 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Palmer and Clegg, 2015 source
Not checked in the free run.
- Premisecitation§ Inflammation and lipid accumulation.
Increased levels of proinflammatory cytokines such as TNF-α and IL-6 found in obesity produce inhibitory effects on Mfn2 expression in human cultured cells.
“the increase of the levels of proinflammatory cytokines such as TNF-α and IL-6 found in obesity produce inhibitory effects on Mfn2 expression in human cultured cells (Bach et al., 2005)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bach et al., 2005 source
Not checked in the free run.
- Premisecitation§ Inflammation and lipid accumulation.
Inflammasome activation in fat tissues will trigger fat cell senescence, a phenomenon connected with SASP.
“the inflammasome activation in fat tissues will trigger fat cell senescence, a phenomenon connected with the senescenceassociated secretory phenotype (SASP) (Newsholme and de Bittencourt, 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Newsholme and de Bittencourt, 2014
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Accumulation of fat during ageing is associated with higher levels of FSH in both men and women.
“the accumulation of fat during ageing with higher levels of follicle-stimulating hormone (FSH) in both men and women (Liu et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Liu et al., 2015 source
Not checked in the free run.
- Premisecitation§ Inflammation and lipid accumulation.
Inflammasome activity has been associated with dysregulation of PPARα and SREBP1c.
“The activity of inflammasome has been associated with dysregulation of PPARα and SREBP1c (Chung et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chung et al., 2015 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Appropriate receptors can interact with these sequences to induce hormone-dependent mitochondrial gene expression.
“The appropriate receptors can interact with these sequences to induce hormone-dependent mitochondrial gene expression (Psarra et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Psarra et al., 2006 source
Not checked in the free run.
- Premisecitation§ Inflammation and lipid accumulation.
Chronically overactive inflammasome activity and production of IL-1β have been associated with abnormal lipid accumulation in old rat liver resulting in steatohepatitis.
“chronically overactive inflammasome activity and production of IL-1β has been associated with the abnormal lipid accumulation in old rat liver resulting in steatohepatitis (Chung et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chung et al., 2015 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
The same effect was found in other breast cancer cell lines.
“The same effect was found in other breast cancer cell lines (SastreSerra et al., 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Sastre-Serra et al., 2013 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
The mitochondrial genome contains sequences similar to nuclear hormone-responsive elements.
“mitochondrial genome contains sequences that are similar to those of nuclear hormone-responsive elements (Sekeris, 1990).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sekeris, 1990
Not checked in the free run.
- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In humans, fat deposits depend on the gender of the individual.
“In humans, fat deposits depend on the gender of the individual (Palmer and Clegg, 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Palmer and Clegg, 2015 source
Not checked in the free run.
- Interpretationcitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Changes in oestrogens during ageing can affect directly the activity of regulators of mitochondria.
“Changes in oestrogens during ageing can also affect directly the activity of regulators of mitochondria.”
Quote in the paperSubstantial claim - Interpretationcitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Mitochondrial dynamics are regulated by sexual hormones.
“mitochondrial dynamics are also regulated by these hormones.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Women with higher subcutaneous fat show less risk for obesity-associated diseases than men with higher visceral fat deposition.
“This will explain why women, with higher levels of subcutaneous fat, show less risk for diseases associated with obesity than men that show higher levels of visceral fat deposition.”
Quote in the paperSubstantial claim- Rests on an assumption: The cause of gender difference in fat distribution resides in sexual hormones.
- Rests on an assumption: Oestrogens and their receptors favour lipid accumulation in subcutaneous depot in women but visceral fat deposition in men.
- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Testosterone therapy in men prevents gain in visceral fat in non-obese ageing men.
“testosterone therapy in men prevents the gain in visceral fat in non-obese ageing men (Allan et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Allan et al., 2008 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In men, decrease in testosterone levels can be responsible for increase of adiposity and fat accumulation in non-adipose tissue during ageing.
“In men, the decrease in testosterone levels can be responsible of the increase of adiposity and fat accumulation in non-adipose tissue during ageing (Mudali and Dobs, 2004).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mudali and Dobs, 2004
Not checked in the free run.
- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Oestrogens directly regulate nuclear DNA-encoded proteins and mitochondrial transcription factors, affecting mitochondrial biogenesis.
“These oestrogens would directly regulate nuclear DNA-encoded proteins and mitochondrial transcription factors affecting by this mechanism mitochondrial biogenesis (Vasconsuelo et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Vasconsuelo et al., 2013 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Accumulation of fat in heart, liver and skeletal muscle during ageing has been attributed to FSH rise since skeletal muscle and liver express FSH-receptor.
“The accumulation of fat in heart, liver and skeletal muscle during ageing has been also attributed to the FSH rise since skeletal muscle and liver also express FSH-receptor (Liu et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Liu et al., 2015 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
These elements have been found in mtDNA accompanied by oestrogen and androgen receptors.
“these elements have been found in mtDNA accompanied by oestrogen and androgen receptors (Demonacos et al., 1995; Demonacos et al., 1996).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In MCF-7 cells, estradiol treatment also induced mitochondrial biogenesis.
“In these cells, estradiol treatment also induced mitochondrial biogenesis (Sastre-Serra et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sastre-Serra et al., 2012 source
Not checked in the free run.
- Interpretationreasoning§ Inflammation and lipid accumulation.
Obesity is responsible for maintenance of a chronic inflammatory status producing a vicious cycle.
“Obesity is, at the same time, responsible of the maintenance of a chronic inflammatory status producing a vicious cycle.”
Quote in the paperSubstantial claim - Interpretationcitation§ Inflammation and lipid accumulation.
The increase in proinflammatory cytokines probably induces dysfunction in mitochondrial homeostasis.
“probably inducing a dysfunction in mitochondrial homeostasis.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
Dysregulation of control of mitochondrial activity and turnover could be associated with dysfunctions in control of satiety.
“a dysregulation of the control of mitochondrial activity and turnover could be also associated with dysfunctions in the control of satiety.”
Quote in the paperSubstantial claim - Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Prohibitin genes are induced by oestrogen receptors.
“prohibitin genes are induced by oestrogen receptors (He et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites He et al., 2011
Not checked in the free run.
- Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
mTOR activity is elevated in POMC neurons in aged mice.
“mTOR activity is elevated in POMC neurons in aged mice.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Yang et al., 2012 source
Not checked in the free run.
- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
In rat models, expression of prohibitins responds to levels of oestrogens in WAT.
“in rat models, the expression of prohibitins responds to the levels of oestrogens in WAT.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Choi et al., 2015 source
Not checked in the free run.
- Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
This increase produces cell hypertrophy that authors associate with obesity-related deterioration of POMC neurons.
“This increase produces cell hypertrophy that the authors associate with obesity-related deterioration of POMC neurons (Yang et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Yang et al., 2012 source
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- Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?
Levels of prohibitins were stimulated by estradiol in WAT and liver in both controls and high-fat fed rats.
“The level of prohibitins were stimulated by estradiol in WAT and liver in both, controls and high-fat fed rats (Choi et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Choi et al., 2015 source
Not checked in the free run.
- Interpretationreasoning§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
Mitochondrial dynamics in NPY/Agrp and POMC neurons play an important role in regulation of energy balance and in diet- and age-related obesity.
“These and other results suggest that mitochondrial dynamics in NPY/Agrp and POMC neurons also play an important role in the regulation of the energy balance and in diet and agerelated obesity.”
Quote in the paperSubstantial claim- Rests on an assumption: Satiety and hunger are controlled by NPY, Agrp and POMC neurons located in the arcuate nucleus of the hypothalamus.
- Rests on an assumption: Both obesity and ageing are associated with rewiring of a principal brain pathway modulating energy homeostasis through promoting reduced activity of satiety POMC neurons.
- Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.
Depletion of Mfn2 in anorexigenic POMC neurons causes severe obesity and leptin resistance probably by affecting ER-stress.
“the depletion of Mfn2 in the anorexigenic POMC neurons causes severe obesity and leptin resistance probably by affecting ER-stress (Schneeberger et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Schneeberger et al., 2013 source
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- Classified as probably not a substantial claim. 75
- May combine two claims. 127
- The quote only partly states this claim. 2
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Premisecitation§ IntroductionThe prevalence of obesity in older people has been considered the major cause of metabolic syndrome.
“the prevalence of obesity in older people has been considered the major cause of metabolic syndrome”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Karakelides et al., 2010 source
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Premisecitation§ IntroductionFat depots sizes in humans reach a peak by middle and early old age.
“Fat depots sizes in humans reach a peak by middle and early old age”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cartwright et al., 2007 source
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Premisenone given§ AbstractThe recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver.
“The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisenone given§ AbstractThese nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy.
“These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ IntroductionLosses of lean mass and shifts to central adiposity have been related to functional decline and considered as predictors of mortality.
“Losses of lean mass and shifts to central adiposity have been related to functional decline and considered as predictors of mortality”
- Also stated in: § Introduction · plain
“Losses of lean mass and shifts to central adiposity have been related to functional decline and considered as predictors of mortality (Kirkland et al., 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kirkland et al., 2002 source
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- Also stated in: § Introduction · plain
Probably not a substantial claim: may not pass S4 (based). May combine two claims.
Premisenone given§ AbstractDysfunction of mitochondria has been associated with ageing and age-related diseases, indicating their importance in the maintenance of cell homeostasis.
“Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ IntroductionIn advanced old age, a decrease in fat tissue occurs, although this decrease has been associated with the accumulation of fat in liver, muscle and bone marrow and other organs.
“in advanced old age, a decrease in fat tissue occurs although this decrease has been associated with the accumulation of fat in liver, muscle and bone marrow and other organs”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kirkland et al., 2002 source
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Premisenone given§ AbstractMitochondria play an essential role in ageing and longevity.
“Mitochondria play an essential role in ageing and longevity.”
- Also stated in: § Abstract · plain
“Mitochondria play an essential role in ageing and longevity.”
Quote in the paperNot a substantial claim- Also stated in: § Abstract · plain
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Premisecitation§ IntroductionChanges in adipose tissue have been recently associated with the development of T2DM.
“changes in adipose tissue have been recently associated with the development of T2DM”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Abranches et al., 2015
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Premisenone given§ AbstractMitochondria are also affected by sexual hormones that suffer drastic changes during ageing.
“Mitochondria are also affected by sexual hormones that suffer drastic changes during ageing.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationreasoning§ IntroductionThe decrease in the capacity to respond to insulin induces ectopic fat deposition in other organs, producing lipotoxicity in muscle, liver and pancreas.
“The decrease in the capacity to respond to insulin induces ectopic fat deposition in other organs producing lipotoxicity in muscle, liver and also in pancreas.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ IntroductionThis redistribution of fat can be related with the preservation of thigh muscle, since loss of thigh muscle was strongly related to mortality whereas no relationship was found with visceral mass.
“This redistribution of fat can be related with the preservation of thight muscle since this study demonstrated a strong relationship between loss of thight muscle and mortality whereas no relationship was found with visceral mass”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Santanasto et al., 2016
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Premisecitation§ IntroductionIn a recent study performed in 70-79 years old men and women, loss of weight was accompanied by the reduction of visceral fat mass and by a gain of intermuscular thigh fat area.
“In a recent study performed in 70-79 years old men and women, it was determined that loss of weight was accompanied by the reduction of visceral fat mass accompanied by a gain of intermuscular thigh fat area”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Santanasto et al., 2016
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Premisecitation§ IntroductionA tendency towards higher visceral adiposity associated with greater morbidity due to increased risk for cardiovascular disease, hypertension and T2DM has been associated with the progression of ageing.
“A tendency towards higher visceral adiposity associated with a greater morbidity due to the increase of risk for cardiovascular disease (CVD), hypertension and T2DM has been associated with the progression of ageing”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matsumoto, 2002
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Premisenone given§ AbstractEmerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation.
“emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation”
- Also stated in: § Abstract · plain
“emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation.”
Quote in the paperNot a substantial claim- Also stated in: § Abstract · plain
Probably not a substantial claim: may not pass S4 (based).
Premisenone given§ AbstractThree major nutritional sensors, mTOR, AMPK and Sirtuins, are involved in the control of mitochondrial physiology.
“Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.SIRT3 knockout mice show repression of PGC1α down regulation and low levels of AMPK phosphorylation after calorie restriction, indicating a key role of this mitochondrial sirtuin in metabolic adaptation to calorie intake.
“SIRT3 KO mice show repression of PGC1α down regulation and low levels of AMPK phosphorylation after CR indicating a key role of this mitochondrial sirtuin in metabolic adaptation to calorie intake”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Palacios et al., 2009
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.SIRT3 levels increase in skeletal muscle after calorie restriction and decrease under high-fat diet feeding, indicating regulation depending on calorie intake.
“SIRT3 levels increase in skeletal muscle after CR and decrease under high-fat diet feeding indicating a regulation depending on the calorie intake”
- Also stated in: § Molecular mechanisms involved in the regulation of mitochondrial physiology. · hedged
“SIRT3 levels increase in skeletal muscle after CR and decrease under high-fat diet feeding indicating a regulation depending on the calorie intake (Palacios et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Palacios et al., 2009
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- Also stated in: § Molecular mechanisms involved in the regulation of mitochondrial physiology. · hedged
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Premisecitation§ IntroductionMitochondria are key organelles in the metabolism of eukaryotic cells.
“Mitochondria are key organelles in the metabolism of eukaryotic cells”
- Also stated in: § Introduction · plain
“Mitochondria are key organelles in the metabolism in of eukaryotic cells (LopezLluch et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Lopez-Lluch et al., 2008
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- cites LopezLluch et al., 2008
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- Also stated in: § Introduction · plain
May combine two claims.
Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.In mammals, calorie restriction induces the expression and activity of sirtuins in many organs, and their activities have been associated with most of the metabolic effects produced by calorie restriction.
“In mammals, CR induces the expression and the activity of sirtuins in many organs and their activities have been associated with most of the metabolic effects produced by CR”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Imai and Guarente, 2010
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.AMPK is one of the major sensitive energy sensors in cells and organisms.
“AMPK is one of the major sensitive energy sensors in cells and organisms.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hardie, 2011 source
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Premisecitation§ IntroductionMitochondrial dysfunction has been associated with a number of age-related diseases such as neurological disorders, CVD, liver and kidney diseases, diabetes and cancer.
“it has been associated with a number of age-related diseases such as neurological disorders, CVD, liver and kidney diseases, diabetes and cancer”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Lane et al., 2015
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- cites Payne and Chinnery, 2015
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- cites Ryan et al., 2015 source
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Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.AMPK inhibits mTORC1 activity both directly and indirectly.
“AMPK also inhibits mTORC1 activity both directly (Gwinn et al., 2008) or indirectly (Inoki et al., 2003).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Premisereasoning§ Molecular mechanisms involved in the regulation of mitochondrial physiology.When nutrients decrease, especially glucose, levels of NAD+ increase and sirtuins are activated.
“When the amount of nutrients decrease, especially in the case of glucose, levels of NAD + increase and sirtuins are then activated.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone given§ IntroductionRegulation of mitochondrial activity in WAT can be associated with the accumulation of fat and a putative disruption of mitochondrial physiology.
“the regulation of mitochondrial activity in WAT can be associated with the accumulation of fat and a putative disruption of mitochondrial physiology”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ IntroductionIn adipose tissue, dysfunctional adipose-like cells appear; they are smaller than normal adipocytes and show a low response to insulin.
“In adipose tissue, dysfunctional adipose-like cells appear. These cells are smaller than normal adipocytes and show a low response to insulin.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kirkland et al., 2002 source
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.mTOR is a complex of different proteins and regulates different pathways involved in angiogenesis, tumour development, insulin resistance, adipogenesis and activation of immune cells.
“This regulator is a complex of different proteins and regulates different pathways involved in angiogenesis, tumour development, insulin resistance, adipogenesis and activation of immune cells”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Laplante and Sabatini, 2009
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.Both mTOR complexes promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation by activating S6K, and downregulate catabolic processes through inhibiting FoxO and autophagy.
“Both complexes promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation by activating ribosomal protein 6 kinase (S6K) and, at the same time, downregulate catabolic processes through inhibiting the transcriptional activity of the forkhead box transcription factors family (FoxO) and autophagy”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S4 (based).
Premisenone given§ IntroductionInformation about the role of mitochondria on white adipose tissue (WAT) is limited in animal models and humans.
“Information about the role of mitochondria on white adipose tissue (WAT) is limited in animal models and humans.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.AMPK and SIRT1 modulate directly PGC1α activity through phosphorylation and deacetylation respectively.
“AMPK and SIRT1, two major metabolic sensors in cells, modulate directly PGC1α activity through phosphorylation and deacetylation respectively”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.Sirtuins are NAD+-dependent deacetylases found in all organisms from prokaryotes to humans and regulate the activity of many enzymes by removing acetyl residues, except mammalian SIRT4 and SIRT5 which show ADP-ribosyl-transferase activity.
“This family of NAD + -dependent deacetylases is found in all the organisms, from prokaryotes to humans, and regulates the activity of many enzymes by removing acetyl residues, except in the case of mammalian SIRT4 and SIRT5 that show ADP-ribosyl-transferase activity”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Santa-Cruz Calvo et al., 2012
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.AMPK is activated in response to an increase of the AMP/ATP ratio, and its activity is reduced when cells are full of energy and the AMP/ATP ratio decreases.
“This kinase is activated in response to the increase of the AMP/ATP ratio, for example, after deprivation of glucose, whereas its activity is reduced when cells are full of energy and the AMP/ATP ratio decreases”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hardie, 2011 source
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Premisecitation§ IntroductionAMPK and sirtuins are activated when energy uptake is limited.
“Opposite regulators are AMP-activated kinase (AMPK) and sirtuins that are activated when energy uptake is limited (Hardie, 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hardie, 2011 source
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Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.It is probable that the incapacity to control mitochondrial dynamics during ageing, when fat accumulates in WAT, liver or muscle, produces the accumulation of damaged mitochondria and consequences such as metabolic unbalance, insulin resistance or oxidative stress.
“It is probable that the incapacity to control mitochondrial dynamics during ageing, when fat accumulates in WAT, liver or muscle, produces the accumulation of damaged mitochondria and the resulting consequences as metabolism unbalance, insulin resistance or oxidative stress.”
Quote in the paperNot a substantial claim- Rests on an assumption: Mitochondrial dysfunction is a cause, not merely a consequence, of fat accumulation and insulin resistance.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Premisenone given§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.To date, there is no information available about the activity of sestrins in adipose tissue and its behaviour during ageing.
“However, to date there is no information available about the activity of sestrins in adipose tissue and its behaviour during ageing.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.Humanin is a 24 amino acid peptide encoded within the 16S ribosomal RNA gene.
“Other mitochondrial-derived peptide is humanin, a 24 aminoacid peptifde encoded within the 16S ribosomal RNA gene (Capt et al., 2016), this peptide has been proposed to produce strong cytoprotective actions against various stress and diseases (Lee et al., 2013a).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Capt et al., 2016
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Premisenone given§ Regulation of AMPK and mTOR controls energy metabolism.FoxO proteins are a family of transcription factors playing key roles in the regulation of cell growth, proliferation, differentiation and longevity.
“These proteins are a family of transcription factors playing key roles in the regulation of cell growth, proliferation, differentiation and longevity.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.In humans, insulin resistance is responsible for the increase of lipids in liver and skeletal muscle and the decrease of the capacity of adipose tissue to store lipids.
“In humans, it has been shown that insulin resistance is responsible of the increase of lipids in liver and skeletal muscle and the decrease of the capacity of adipose tissue to store lipids (Toledo and Goodpaster, 2013).”
- Also stated in: § Metabolic syndrome, fat accumulation and mitochondria. · plain
“In humans, it has been shown that insulin resistance is responsible of the increase of lipids in liver and skeletal muscle and the decrease of the capacity of adipose tissue to store lipids (Toledo and Goodpaster, 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Toledo and Goodpaster, 2013
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- Also stated in: § Metabolic syndrome, fat accumulation and mitochondria. · plain
May combine two claims.
Premisecitation§ Inflammation and lipid accumulation.Casp-1 activates pathways that precipitate mitochondrial disassembly, increase ROS production and break up mitochondrial network, triggering a vicious cycle in which mitochondrial dysfunction activates inflammasome and Casp-1 induces mitochondrial dysfunction.
“On the other hand, Casp-1 activates several pathways that precipitate mitochondrial disassembly, increase ROS production and breaks up mitochondrial network, triggering a vicious cycle in which mitochondrial dysfunction activates inflammasome and Casp-1 induces mitochondrial dysfunction (Yu et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Yu et al., 2014
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Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?Changes in oestrogen levels can modulate the genetic expression of mitochondrial factors and be responsible for mitochondrial dysfunction effect in fat accumulation during ageing.
“Changes in oestrogens levels can also modulate the genetic expression of mitochondrial factors and then, be also responsible of mitochondrial dysfunction effect in fat accumulation during ageing (Vasconsuelo et al., 2013).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Vasconsuelo et al., 2013 source
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Interpretationcitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?An oestrogen-dependent effect can induce accumulation of fat and probably insulin resistance in muscle.
“This suggests that an oestrogendependent effect can induce accumulation of fat and probably insulin resistance in muscle.”
- Also stated in: § Does fat accumulation and mitochondrial dysfunction depend on sexual hormones? · hedged
“This suggests that an oestrogendependent effect can induce accumulation of fat and probably insulin resistance in muscle.”
Quote in the paperSubstantial claim- Also stated in: § Does fat accumulation and mitochondrial dysfunction depend on sexual hormones? · hedged
May combine two claims.
Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.Metabolic inflexibility is present in obese people, who oxidize lipids in insulin-stimulated conditions instead of metabolizing glucose, with mitochondria being key organelles affecting this incapacity.
“This impairment is known as 'metabolic inflexibility' (Griffin et al., 2015), that is present in obese people since they are able to oxidize lipids in insulin-stimulated conditions instead to metabolize glucose being mitochondria the key organelles affecting this incapacity (Storlien et al., 2004).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Storlien et al., 2004 source
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Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?Men tend to accumulate visceral fat whereas women accrue more subcutaneous depots prior to menopause, but after menopause fat depots in women shift to visceral depots.
“Men tend to accumulate visceral fat whereas women accrue more subcutaneous depots prior to menopause but, after menopause, fat depots in women shift to visceral depots (Palmer and Clegg, 2015).”
- Also stated in: § Does fat accumulation and mitochondrial dysfunction depend on sexual hormones? · plain
“Men tend to accumulate visceral fat whereas women accrue more subcutaneous depots prior to menopause but, after menopause, fat depots in women shift to visceral depots (Palmer and Clegg, 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Palmer and Clegg, 2015 source
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- Also stated in: § Does fat accumulation and mitochondrial dysfunction depend on sexual hormones? · plain
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Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?Oestrogens and their receptors favour lipid accumulation in subcutaneous depot in women but visceral fat deposition in men.
“The cause of this difference resides in sexual hormones. Oestrogens and their receptors favour lipid accumulation in subcutaneous depot in women but visceral fat deposition in men.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Palmer and Clegg, 2015 source
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Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.Deficiency in AMPK results in glucose intolerance, lower physical capacity and obesity, symptoms of metabolic disease.
“Moreover, deficiency in AMPK results in glucose intolerance, lower physical capacity and obesity; symptoms of metabolic disease (Steinberg et al., 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Steinberg et al., 2010
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Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?The increase of FSH is responsible for fat accumulation and affects fat redistribution from subcutaneous and abdominal fat to visceral fat.
“In this paper, authors indicate that the increase of this hormone not only is responsible for fat accumulation but also affects fat redistribution from subcutaneous and abdominal fat to visceral fat, a fact associated with ageing (Zamboni et al., 2005).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Liu et al., 2015
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- cites Zamboni et al., 2005
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Premisecitation§ Inflammation and lipid accumulation.NLRP3 inflammasome activity is essential in the development of high-fat diet-induced obesity and insulin resistance.
“Furthermore, a NLRP3 KO mice model has demonstrated that the activity of this inflammasome is essential in the development of high-fat dietinduced obesity and in the development of insulin resistance (Stienstra et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Stienstra et al., 2011 source
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Interpretationcitation§ Inflammation and lipid accumulation.Fat accumulation promotes inflammasome-associated SASP that induces cellular senescence in other tissues, aggravating obesity-dependent chronic inflammation in another vicious cycle.
“Then, fat accumulation would promote inflammasome associated SASP that would induce cellular senescence in other tissues of the organism aggravating by this mechanism the obesity-dependent chronic inflammation in another vicious cycle (Newsholme and de Bittencourt, 2014) (Fig.3).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Newsholme and de Bittencourt, 2014
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Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?Visceral fat accumulation is associated with many age-related diseases and with fat accumulation in heart, liver and skeletal muscle, increasing risk for insulin resistance and cardiovascular disease.
“Visceral fat accumulation is associated with many age-related diseases (Huffman and Barzilai, 2009) accompanied by the accumulation of fat in tissues such as the heart, liver and skeletal muscle which increases risk for insulin resistance and cardiovascular disease (Kuk et al., 2009).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Huffman and Barzilai, 2009 source
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- cites Kuk et al., 2009
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Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?In rats, reduction of oestrogens produced by ovariectomy decreases PGC1α expression and reduces β-oxidation in muscle.
“In rats, a model of menopause by using ovariectomization suggested that reduction of oestrogens produced the decrease of PGC1α expression and the reduction of β-oxidation in muscle (Cavalcanti-de-Albuquerque et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cavalcanti-de-Albuquerque et al., 2014
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Interpretationreasoning§ Inflammation and lipid accumulation.Obesity is responsible for maintaining a chronic inflammatory status, producing a vicious cycle.
“Obesity is, at the same time, responsible of the maintenance of a chronic inflammatory status producing a vicious cycle.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?In premenopausal women, oestrogens protect against weight gain by increasing energy expenditure, whereas postmenopausal women gain weight by the natural decrease in endogenous estradiol levels.
“In premenopausal women, oestrogens protect against weight gain by increasing energy expenditure, whereas postmenopausal women gain weight by the natural decrease in endogenous estradiol levels (Gambacciani et al., 1997).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gambacciani et al., 1997 source
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Interpretationreasoning§ Inflammation and lipid accumulation.Mitochondria can be at the origin of overactivation of inflammasome in liver and other organs, leading to fat accumulation and steatohepatitis.
“These studies suggest that mitochondria can be on the origin of the overactivation of inflammasome in liver and other organs and then, accumulation of fat and development of steatohepatitis.”
Quote in the paperSubstantial claim- Rests on an assumption: Mitochondrial dysfunction is a cause, not merely a consequence, of fat accumulation and insulin resistance.
May combine two claims.
Premisecitation§ Inflammation and lipid accumulation.In patients with diabetes, inhibition of autophagy results in accumulation of dysfunctional mitochondria leading to higher ROS production and activating inflammasome.
“In patients with diabetes, the inhibition of autophagy results in the accumulation of dysfunctional mitochondria leading to higher ROS production and activating inflammasome (Harijith et al., 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Harijith et al., 2014
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Premisenone given§ AbstractDuring ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological functions in the organism.
“During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological functions activities in the organism.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone given§ References.Mitochondrial damage induces inflammasome activity in adipocyte-derived proinflammatory cytokines.
“Mitochondrial damage induces inflammasome activity in adipocytes-derives proinflammatory cytokines.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Premisenone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.AMPK and mTOR1 regulate these processes.
“Regulation of these processes by AMPK and mTOR1 regulate these processes.”
Quote in the paperNot a substantial claimThe quote only partly states this claim.
Interpretationreasoning§ Figure legends.AMPK/SIRT maintain a mitochondrial balanced activity.
“maintaining a mitochondrial balanced activity.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Premisenone given§ References.Estrogens regulate mitochondrial activity and affect age-dependent fat depots.
“Estrogens regulate mitochondrial activity and affect age-dependent fat depots.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Do fat accumulation and mitochondrial dysfunction depend on sexual hormones?In the human breast cancer cell line MCF-7, estradiol treatment increases mRNA levels of mitochondrial fusion genes and decreases FIS1 gene expression.
“In the human breast cancer cell line MCF-7, the mRNA levels of mitochondrial fusion genes increase during estradiol treatment whereas FIS1 gene expression decreases (Sastre-Serra et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sastre-Serra et al., 2012
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Interpretationnone given§ Figure legends.Fat accumulation of T2DM activates mTORC1.
“High fat diets, fat accumulation of T2DM activates mTORC1”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone given§ Figure legends.mTORC1 reduces lipid consumption by affecting mitochondrial biogenesis, turnover and dynamics through inhibiting PGC1α.
“mTORC1 that reduces lipid consumption by affecting mitochondrial biogenesis, turnover and dynamics through inhibiting PGC1α.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone given§ Figure legends.High fat diets activate mTORC1.
“High fat diets, fat accumulation of T2DM activates mTORC1”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone given§ Figure legends.Mitochondrial homeostasis is basic to maintain a balanced metabolic activity in fat-accumulating tissues including adipose tissue, muscle and liver.
“Mitochondrial homeostasis is basic to maintain a balanced metabolic activity in fat accumulating tissues including adipose tissue, muscle and liver.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationreasoning§ Figure legends.AMPK/SIRT inhibit mTORC1.
“AMPK/SIRT that inhibit mTORC1”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Visceral fat accumulation is associated with the appearance and impairment of T2DM, evolution of hepatosteatosis and obesity.
“Visceral fat accumulation is associated with the appearance and impairment of T2DM, evolution of hepatosteatosis and obesity.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Age-dependent oestrogen decay affects mitochondrial dynamics by decreasing mitochondrial fusion and PGC1α activity.
“Age-dependent oestrogen decay will affect mitochondrial dynamics by decreasing mitochondrial fusion and PGC1α activity.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone given§ IntroductionAgeing is a natural and progressive process occurring in all living organisms and characterized by deterioration of structure and functional capacities.
“Ageing is a natural and progressive process occurring in all living organisms and characterized by the deterioration of structure and functional capacities.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). The quote only partly states this claim.
Interpretationreasoning§ Figure legends.A dysfunction in these factors can cause small and damaged mitochondria.
“or small and damaged mitochondria”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone given§ References.Mitochondrial dynamics are key components in fat and aging.
“Mitochondrial dynamics are key components in fat and aging.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Balanced activity of mitochondria is essential to control satiety and prevent the appearance and progression of T2DM, obesity and inflammation.
“The balanced activity of mitochondria is essential to control satiety and prevent the appearance and progression of T2DM, obesity and inflammation”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Fission is regulated by DRP1 and FIS1.
“DRP1 and FIS1 (fission)”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationreasoning§ Concluding remarks.This regulation is affected by sexual hormones that change during ageing, and probably the reduction of oestrogens is one of the key factors involved in mitochondrial dysfunction and fat accumulation in humans.
“This regulation is affected by sexual hormones that change during ageing and probably the reduction of oestrogens is one of the key factors involved in mitochondrial dysfunction and fat accumulation in humans.”
Quote in the paperNot a substantial claim- Rests on an assumption: Findings from animal models (mice, rats, worms) about mitochondrial function and fat metabolism can be extrapolated to humans.
May combine two claims.
Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Prolongevity interventions improve the progression of ageing and fat accumulation during ageing.
“improve the progression of ageing and fat accumulation during ageing.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone given§ AbstractThree main nutritional sensors, mTOR, AMPK and Sirtuins, are involved in the control of mitochondrial physiology.
“Three mainmajor nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ IntroductionAgeing is multifactorial involving genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intracellular communication.
“Ageing is multifactorial involving different molecular and cellular processes such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intracellular communication (Kennedy et al., 2014; Lopez-Otin et al., 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S4 (based). May combine two claims.
Interpretationnone given§ Figure legends.CR, exercise or polyphenols activate AMPK/SIRT.
“effectors such as CR, exercise of polyphenols activate AMPK/SIRT”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone given§ Figure legends.Prolongevity factors such as calorie restriction, exercise or polyphenols can reduce mitochondrial dysfunction by maintaining mitochondrial biogenesis, fusion/fission balance and mito- and autophagy during ageing.
“Prolongevity factors such as calorie restriction, exercise or several nutraceutical such as polyphenols can reduce mitochondrial dysfunction by maintaining mitochondrial biogenesis, fusion/fission balance and mito- and autophagy during ageing”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionA tendency towards higher visceral adiposity associated with greater morbidity due to increased risk for cardiovascular disease, hypertension and type 2 diabetes mellitus has been associated with progression of ageing.
“A tendency towards higher visceral adiposity associated with a greater morbidity due to the increase of risk for cardiovascular disease (CVD), hypertension and T2DM is has been associated with the progression of ageing (Matsumoto, 2002).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matsumoto, 2002
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Interpretationnone given§ Concluding remarks.During ageing, a tendency to increase fusion in mitochondria has been reported in order to maintain mitochondrial activity; however, fat accumulation induces a higher activity of fission mechanisms promoting the accumulation of small and less efficient mitochondria.
“During ageing a tendency to increase fusion in mitochondria has been reported in order to maintain mitochondrial activity; however, fat accumulation induces a higher activity of fission mechanisms promoting the accumulation of small and less efficient mitochondria.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Premisenone given§ AbstractMitochondria are affected by sexual hormones that suffer drastic changes during ageing.
“Mitochondria are also affected by sexual hormones that suffer drastic changes during ageing.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone given§ Concluding remarks.Regulators of metabolism such as mTOR, AMPK and sirtuins are involved in the effect of mitochondrial dysfunction on obesity and age-related diseases, and the complex equilibrium between their activities modulates mitochondrial biogenesis, dynamics and turnover.
“Regulators of metabolism such as mTOR, AMPK and sirtuins are involved in this effect and the complex equilibrium between their activities modulates mitochondrial biogenesis, dynamics and turnover.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Small and damaged mitochondria increase ROS production by decreasing fusion mechanisms and blocking autophagy processes.
“that increase ROS production by decreasing fusion mechanisms and blocking autophagy processes.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Ageing, high fat diet and sexual hormones decay cause mitochondrial dysfunction.
“Ageing, high fat diet and sexual hormones decay causes mitochondrial dysfunction”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionAgeing is characterized by the appearance of chronic diseases such as sarcopenia, type 2 diabetes mellitus, cardiovascular disease, hypercholesterolemia, hypertension or neurodegenerative diseases.
“Ageing is also characterized by the appearance of different chronic diseases such as sarcopenia, type 2 diabetes mellitus (T2DM), cardiovascular disease, hypercholesterolemia, hypertension or neurodegenerative diseases among others (Kennedy et al., 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kennedy et al., 2014 source
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Interpretationreasoning§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.T2DM, obesity and inflammation are hallmarks of age-dependent accumulation of fat.
“hallmarks of age-dependent accumulation of fat.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone given§ Fig. 2. Mitochondrial dynamics during fat accumulation and ageing.Fusion is regulated by Mfn1 and 2, OPA1 and prohibitins.
“regulated by Mfn1 and 2, OPA1 and prohibitins (fusion)”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone given§ Figure legends.Decay of oestrogens produces an imbalance in mitochondrial homeostasis.
“Ageing and the decay of oestrogens produce an unbalance in mitochondrial homeostasis”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationreasoning§ Concluding remarks.Probably these two opposite processes end in the accumulation of damaged mitochondria that increase oxidative damage that contribute to the appearance and impairment of insulin resistance, metabolic dysfunction and the release of proinflammatory mediators.
“Probably these two opposite processes end in the accumulation of damaged mitochondria that increase oxidative damage that contribute to the appearance and impairment of insulin resistance, metabolic dysfunction and the release of proinflammatory mediators.”
Quote in the paperSubstantial claim- Rests on an assumption: Mitochondrial dysfunction is a cause, not merely a consequence, of fat accumulation and insulin resistance.
Probably not a substantial claim: may not pass S4 (based).
Interpretationreasoning§ Figure legends.Decay of mito- and autophagy processes is also affected by these events.
“Decay of mito- and autophagy processes is also affected.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone given§ Figure legends.mTOR and AMPK/SIRT are two major systems involved in the control of metabolism in cells.
“Two major systems are involved in the control of metabolism in cells: mTOR and AMPK/SIRT.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Regulation of AMPK and mTOR controls energy metabolism.mTORC1 negatively regulates autophagy through phosphorylating ULK-1 and ULK-2 in inhibitory sites, whereas AMPK positively regulates autophagy by phosphorylating these proteins in activating sites.
“Whereas mTORC1 negatively regulates autophagy through phosphorylating the mediators, unc-51-like kinase 1/2 (ULK-1 and ULK-2), in inhibitory sites (Chan, 2009; Kim et al., 2011), AMPK positively regulates autophagy by phosphorylating these proteins in their activating sites (Alers et al., 2012).”
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- cites Alers et al., 2012
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Premisenone given§ IntroductionInformation about the role of mitochondria in white adipose tissue is limited in animal models and humans.
“Information about the role of mitochondria on white adipose tissue (WAT) is limited in animal models and humans.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisenone given§ IntroductionDecreased capacity to respond to insulin induces ectopic fat deposition in other organs, producing lipotoxicity in muscle, liver and pancreas.
“The incapacity decrease in the capacity to respond to insulin induces ectopic fat deposition in other organs producing lipotoxicity in muscle, liver and also in pancreas.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Interpretationnone given§ Molecular mechanisms involved in the regulation of mitochondrial physiology.These mechanisms regulate each other in all organisms studied in an evolutionary conserved response that avoids fruitless energy expenditure and uses recycled structures to maintain organisms' survival.
“Interestingly, these mechanisms regulate each other in all the organisms studied in an evolutionary conserved response that avoids fruitless energy expenditure and use recycled structures to maintain organisms' survival.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ IntroductionIn adipose tissue, dysfunctional adipose-like cells appear; they are smaller than normal adipocytes and show low response to insulin.
“In adipose tissue, dysfunctional adipose-like cells appear. These cells are smaller than normal adipocytes and show a low response to insulin.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kirkland et al., 2002 source
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Premisecitation§ IntroductionIn 70-79 year old men and women, weight loss was accompanied by reduction of visceral fat mass and gain of intermuscular thigh fat area.
“In a recent study performed in 70-79 years old men and women, it was determined that loss of weight was accompanied by the reduction of visceral fat mass accompanied by a gain of intermuscular thigh fat area (Santanasto et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Santanasto et al., 2016
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.SIRT3 is located in mitochondria and plays an important role in regulation of mitochondrial activity, especially in fat metabolism.
“SIRT3, a member located in the mitochondria, seems to be very importanta very important role in the regulation of mitochondrial activity especially in fat metabolism (Kendrick et al., 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kendrick et al., 2011
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.SIRT3 regulates electron transport chain complex II activity, Mn-SOD activity, and autophagy by deacetylation of FOXO3.
“SIRT3 has been also involved in the regulation by deacetylation of electron transport chain complex II activity (Kendrick et al., 2011), modulation of the activity of Mn-SOD (Qiu et al., 2010) or regulation of autophagy by deacetylation of FOXO3 (Kume et al., 2010).”
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Premisecitation§ IntroductionPrevalence of obesity in older people has been considered the main cause of metabolic syndrome.
“Thus, the prevalence of obesity in older people has been considered the main major cause of metabolic syndrome (Karakelides et al., 2010)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Karakelides et al., 2010 source
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.mTOR is a complex of different proteins and regulates pathways involved in angiogenesis, tumour development, insulin resistance, adipogenesis and activation of immune cells.
“This regulator is a complex of different proteins and regulates different pathways involved in angiogenesis, tumour development, insulin resistance, adipogenesis and activation of immune cells (Laplante and Sabatini, 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Laplante and Sabatini, 2009
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.eNOS is induced by calorie restriction in mice and human muscle and is essential in calorie restriction-induced mitochondrial biogenesis, since in eNOS-/- mice this induction is blocked.
“it has been demonstrated that eNOS is induced by CR in mice and human muscle (Civitarese et al., 2007; Nisoli et al., 2005) being essential in the CR-induced mitochondrial biogenesis since in eNOS -/- mice this induction is blocked (Nisoli et al., 2005).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Civitarese et al., 2007 source
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- cites Nisoli et al., 2005
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Premisereasoning§ Molecular mechanisms involved in the regulation of mitochondrial physiology.When nutrients decrease, especially glucose, NAD+ levels increase and sirtuins are activated.
“When the amount of nutrients decrease, especially in the case of glucose, levels of NAD + increase and sirtuins are then activated.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.Both mTOR complexes promote transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation by activating S6K, and downregulate catabolic processes through inhibiting FoxO and autophagy.
“Both complexes promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation by activating ribosomal protein 6 kinase (S6K) and, at the same time, downregulate catabolic processes through inhibiting the transcriptional activity of the forkhead box transcription factors family (FoxO) and autophagy (Duvel et al., 2010; Wullschleger et al., 2006).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.PGC1alpha stimulates mitochondrial biogenesis, regulates mitochondrial dynamics, modulates oxidative phosphorylation and controls mitochondrial genome copy number.
“PGC1α) is the central factor involved in the regulation of mitochondrial mass and the adaptation to energy demand since this transcriptional coactivator stimulates mitochondrial biogenesis, regulates mitochondrial dynamics, modulates oxidative phosphorylation and controls mitochondrial genome copy number (Gouspillou et al., 2014; Handschin and Spiegelman, 2006).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Gouspillou et al., 2014
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- cites Handschin and Spiegelman, 2006
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.Sirtuins are NAD+-dependent deacetylases found in all organisms from prokaryotes to humans and regulate activity of many enzymes by removing acetyl residues, except mammalian SIRT4 and SIRT5 which show ADP-ribosyl-transferase activity.
“This family of NAD + -dependent deacetylases is found in all the organisms, from prokaryotes to humans, and regulates the activity of many enzymes by removing acetyl residues, except in the case of mammalian SIRT4 and SIRT5 that show ADP-ribosyl-transferase activity (Santa-Cruz Calvo et al., 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Santa-Cruz Calvo et al., 2012
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Premisecitation§ IntroductionChanges in adipose tissue have been recently associated with development of type 2 diabetes mellitus.
“changes in adipose tissue have been recently associated with the development of T2DM (Abranches et al., 2015).”
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.AMPK is activated in response to increase of AMP/ATP ratio, for example after glucose deprivation, and its activity is reduced when cells are full of energy and AMP/ATP ratio decreases.
“This kinase is activated in response to the increase of the AMP/ATP ratio, for example, after deprivation of glucose, whereas its activity is reduced when cells are full of energy and the AMP/ATP ratio decreases (Hardie, 2011).”
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Premisecitation§ IntroductionFat depot sizes in humans reach a peak by middle and early old age.
“Fat depots sizes in humans reach a peak by middle and early old age (Cartwright et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cartwright et al., 2007 source
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.SIRT3 knockout mice show repression of PGC1alpha and low levels of AMPK phosphorylation after calorie restriction, indicating a key role of SIRT3 in metabolic adaptation to calorie intake.
“SIRT3 KO mice show repression of PGC1α down regulation and low levels of AMPK phosphorylation after CR indicating a key role of this mitochondrial sirtuin in metabolic adaptation to calorie intake (Palacios et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Palacios et al., 2009
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Premisecitation§ IntroductionmTOR is activated by high calorie intake or high levels of amino acids.
“One of these regulators is the mammalian Target of Rapamycin (mTOR) which is activated by high calorie intake or high levels of aminoacids (Laplante and Sabatini, 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Laplante and Sabatini, 2009
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Premisecitation§ IntroductionIn that study, loss of thigh muscle was strongly related to mortality, whereas no relationship was found with visceral mass.
“this study demonstrated a strong relationship between loss of thight muscle and mortality whereas no relationship was found with visceral mass (Santanasto et al., 2016).”
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Premisenone given§ Molecular mechanisms involved in the regulation of mitochondrial physiology.mTOR is present in two complexes, mTORC1 and mTORC2.
“It is present in two different complexes, mTOR complex I (mTORC1) and mTOR complex II (mTORC2).”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ IntroductionIn advanced old age, a decrease in fat tissue occurs, associated with accumulation of fat in liver, muscle, bone marrow and other organs.
“However, in advanced old age, a decrease in fat tissue occurs although this decrease has been associated with the accumulation of fat in liver, muscle and bone marrow and other organs (Kirkland et al., 2002).”
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.AMPK is one of the main sensitive energy sensors in cells and organisms.
“AMPK is one of the mainmajor sensitive energy sensors in cells and organisms.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.In mammals, calorie restriction induces expression and activity of sirtuins in many organs, and their activities have been associated with most metabolic effects produced by calorie restriction.
“In mammals, CR induces the expression and the activity of sirtuins in many organs and their activity activities has have been associated with most of the metabolic effects found in these organisms afterproduced by CR (Imai and Guarente, 2010).”
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Premisecitation§ Molecular mechanisms involved in the regulation of mitochondrial physiology.AMPK and SIRT1 directly modulate PGC1alpha activity through phosphorylation and deacetylation, respectively.
“AMPK and SIRT1, the two mainmajor metabolic sensors in cells, modulate directly are direct modulators of PGC1α activity through phosphorylation and deacetylation respectively (Jager et al., 2007; Nemoto et al., 2005).”
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Premisenone given§ Mitochondrial activity and turnover are affected during ageing.Mitochondrial dynamics are regulated by a group of proteins that regulate fusion and fission in mitochondria.
“Mitochondrial dynamics are regulated by a group of proteins that regulate fusion and fission in mitochondria.”
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Premisenone given§ Mitochondrial activity and turnover are affected during ageing.The main proteins involved in mitochondrial fission are dynamin related protein 1 (DRP1) and fission protein 1 (FIS1).
“The mainmajor proteins involved in mitochondrial fission are dynamin related protein 1 (DRP1) and fission protein 1 (FIS1).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisenone given§ Mitochondrial activity and turnover are affected during ageing.Mitofusins are located at the outer membrane of mitochondria acting in fusion of these membranes whereas OPA1 is located in the intermembrane space and acts in fusion of the inner membranes.
“Mitofusins are located at the outer membrane of mitochondria acting in the fusion process of these membranes whereas OPA1 is located in the intermembrane space and acts in the fusion of the inner membranes.”
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.The main proteins involved in mitochondrial fusion are mitofusins 1 and 2 (Mfn1 and Mfn2) and autosomal dominant optic atrophy-1 (OPA1).
“The mainmajor proteins involved in fusion are mitofusins 1 and 2 (Mfn1 and Mfn2) and autosomal dominant optic atrophy-1 (OPA1) (Wai and Langer, 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wai and Langer, 2016
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Premisenone given§ Mitochondrial activity and turnover are affected during ageing.Damaged mitochondria show low efficiency producing lower ATP and higher release of ROS through deficient activity of the mitochondrial electron transport chain complexes.
“damaged mitochondria show low efficiency producing lower ATP and higher release of ROS through a deficient activity of the mitochondrial electron transport chain complexes.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Mitochondrial activity and turnover are affected during ageing.Mitochondrial fusion is associated with optimized mitochondria whereas fission is associated with damaged mitochondria and their removal by mito- or autophagy.
“Mitochondrial fusion is associated with optimized mitochondria whereas fission is associated with damaged mitochondria and their removal by mito- or autophagy (Lopez-Lluch et al., 2008).”
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Premisenone given§ Regulation of AMPK and mTOR controls energy metabolism.FoxO proteins are transcription factors playing key roles in regulation of cell growth, proliferation, differentiation and longevity.
“These proteins are a family of transcription factors playing key roles in the regulation of cell growth, proliferation, differentiation and longevity.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Mitochondrial activity and turnover are affected during ageing.Most data suggest that there is an increase in oxidative damage in the elderly affecting senescence, fertility decline, skin ageing, neutrophils' activity or skeletal muscle.
“most data suggest that there is an increase in oxidative damage in the elderly affecting senescence (Lu and Finkel, 2008), fertility declining (Benkhalifa et al., 2014), skin ageing (Kammeyer and Luiten, 2015), neutrophils' activity (Kovalenko et al., 2014) or skeletal muscle (McDonagh, 2016).”
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.Mfn2 is associated in the connection between mitochondria and the endoplasmic reticulum, playing a role in the development of ER stress and fat accumulation in conditions of metabolic stress.
“Mfn2 is also associated in the connection between mitochondria and the endoplasmic reticulum (ER) playing a role in the development of endoplasmic reticulum (ER) stress and fat accumulation in conditions of metabolic stress (de Brito and Scorrano, 2008, 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites de Brito and Scorrano, 2008, 2009
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.A decrease of the fission process would allow mitochondria to escape autophagic degradation and maintain enough ATP production even with deficient mitochondria.
“Thus, the decrease of fission process would allow mitochondria to escape autophagic degradation and then, to maintainmaintaining enough ATP production even with deficient mitochondria (Gomes and Scorrano, 2011).”
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.Other factors such as mitochondrial fission factor (Mff) or mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51) can also mediate DRP1 recruitment in absence of FIS1.
“other factors such as mitochondrial fission factor (Mff) or mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51) can also mediate DRP1 recruitment in absence of FIS1 (Loson et al., 2013; Shen et al., 2014)”
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Premisenone given§ Mitochondrial activity and turnover are affected during ageing.It is not clear how different mitochondrial morphologies affect mitochondrial function.
“It is not clear, how different morphologies affect mitochondrial function, although changes in mitochondrial shape during development suggest a close relationship between morphology and function.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.SIRT3 deacetylates OPA1, elevating its GTPase activity and increasing fusion processes.
“SIRT3 also emerges as an important factor in the control of mitochondrial dynamics during ageing since it deacetylates OPA1 elevating its GTPase activity and then, increasing fusion processes (Samant et al., 2014).”
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.Accumulation of damaged mitochondria during ageing or by high-fat diet increases the production of ROS that can produce damage in molecules and structures and modulate cell responses such as antioxidant response, removal of damaged molecules, induction of organelle turnover and regulation of mitochondrial activity.
“Accumulation of damaged mitochondria during ageing or by high-fat diet increases the production of ROS that can not only produce damage in molecules and structures but also modulate cell responses such as antioxidant response, removal of damaged molecules, induction of organelle turnover and regulation of mitochondrial activity (Ristow, 2014).”
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Interpretationreasoning§ Mitochondrial activity and turnover are affected during ageing.During ageing, the equilibrium of fusion and fission is disturbed, producing the accumulation of damaged mitochondria.
“During ageing, the equilibrium of fusion and fission is disturbed producing the accumulation of damaged mitochondria.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.Mul1 controls mitochondrial dynamics by inducing fission and reducing fusion by inducing Mfn2 degradation.
“Then, Mul1 controls mitochondrial dynamics by inducing fission at the same time that reduce fusion by inducing Mfn2 degradation (Peng et al., 2016).”
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Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.PGC1β can be a candidate factor controlling mitochondrial dynamics because it controls basal mitochondrial biogenesis and stimulates mitochondrial fusion through modulation of Mfn2.
“Among them PGC1β can be one of the candidates since this transcription factor control basal mitochondrial biogenesis and stimulates mitochondrial fusion through the modulation of Mfn2 (Liesa et al., 2008)”
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Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.The protective effect of sestrins depends on the promotion of autophagic degradation of Keaps 1 and Nrf2 activation by inhibition of mTORC1, probably by eliminating damaged mitochondria.
“it has been recently demonstrated that the protective effect of sestrins depends on the promotion of autophagic degradation of Keaps 1 and Nrf2 activation by inhibition of mTORC1 (Rhee and Bae, 2015) probably by eliminating damaged mitochondria as in the case of rat kidney cells (Ishihara et al., 2013).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Rhee and Bae, 2015
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- cites Ishihara et al., 2013
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.DRP1 is recruited on the outer mitochondrial membrane by FIS1 which is already inserted in this membrane.
“DRP1 is recruited on the outer mitochondrial membrane by FIS1 which is already inserted in this membrane (Santel and Frank, 2008; Yoon et al., 2003).”
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- cites Yoon et al., 2003
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.Senescence is accompanied by higher production of ROS and lower mitochondrial respiratory activity.
“accompanied by higher production of ROS and lower mitochondrial respiratory activity (Yoon et al., 2006).”
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Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.The factors that control the change in mitochondrial dynamics during ageing have not been determined yet.
“Unfortunately the factors that control the change in mitochondrial dynamics during ageing have not been determined yet (Collins et al., 2002).”
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.Low levels of ROS have been involved in the modulation of glucose metabolism and the increase in oxidative metabolism and stress resistance in CR conditions or after exercise, indicating a role of ROS in the regulation of metabolism.
“Low levels of ROS have been also involved in the modulation of glucose metabolism and the increase in oxidative metabolism and stress resistance in CR conditions or after exercise indicating a role of ROS in the regulation of metabolism (Barbieri et al., 2013).”
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Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.Treatment with MOTS-C in mice prevents age-dependent and high-fat diet induced insulin resistance and obesity, indicating an important role of mitochondria in the control of fat metabolism and probably producing prolongevity effects.
“treatment with MOTS-C in mice prevent agedependent and high-fat diet induced insulin resistance and obesity indicating an important role of mitochondria in the control of fat metabolism probably producing prolongevity effects (Fuku et al., 2015; Lee et al., 2015).”
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- cites Lee et al., 2015 source
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.DRP1 is a GTPase protein located mainly in the cytosol although a fraction is localized to punctate on mitochondria.
“DRP1 is also a GTPase protein located mainly in the cytosol although a fraction is localized to punctate on mitochondria (Smirnova et al., 2001).”
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.A decrease in the levels of mitochondrial fission proteins can be an adaptive response to increase resistance against oxidative stress, promoting a resistance phenotype in response to higher ROS production by mitochondrial dysfunction.
“it has been recently proposed that a decrease in the levels of mitochondrial fission proteins can be an adaptive response to increase the resistance against oxidative stress promoting a resistance phenotype in response to a higher ROS production by mitochondrial dysfunction (Mai et al., 2010)”
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Premisecitation§ Mitochondrial turnover can be regulated by different factors during ageing.Multiple factors affect mitochondrial activity and many of them have been associated with cell senescence and ageing.
“Multiple factors affect mitochondrial activity and many of them have been associated with cell senescence and ageing as has been recently reviewed (Ziegler et al., 2015).”
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Premisecitation§ Mitochondrial activity and turnover are affected during ageing.The effect of fusion capacity on respiration was reversed by restoring Mfn and OPA1 proteins and was not a consequence of changes in biogenesis regulators such as PGC1α, indicating a direct relationship of mitochondrial dynamics and regulation of OXPHOS subunits activities.
“This effect is was reversed by restoring Mfn and OPA1 proteins and was not a consequence of changes in biogenesis regulators such as PGC1α, indicating a direct relationship of mitochondrial dynamics and regulation of OXPHOS subunits activities (Chen et al., 2005).”
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Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Balanced mitochondrial dynamics is important in the physiology of adipose and other tissues, and the regulation of different factors involved in mitochondrial fusion and fission is complex.
“All these facts highlight the importance of a balanced mitochondrial dynamics in the physiology adipose and other tissues and the complex regulation of the different factors involved in mitochondrial fusion and fission.”
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Hyperplasia has been associated with dysregulation of metabolism in adipocytes and enhanced differentiation in adipocytes.
“Interestingly, hyperplasia has been also associated with dysregulation of metabolism in adipocytes and enhanced differentiation in adipocytes (Abdesselem et al., 2016).”
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.This reduction is directly proportional to BMI and inversely proportional to insulin response.
“This reduction is directly proportional to BMI and inversely proportional to insulin response (Pich et al., 2005).”
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Mfn2 depleted rat muscle cells show reduced proton leak and lower bioenergetics efficiency indicated by lower glucose oxidation and mitochondrial respiration.
“Mfn2 depleted rat muscle cells show a reduced proton leak and lower bioenergetics efficiency indicated by lower glucose oxidation and mitochondrial respiration (Bach et al., 2003).”
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Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.These pharmaceutical compounds are promising in modulation of mitochondrial activity in ageing and obesity although more studies are needed to demonstrate their effectivity in mammals and humans.
“These results demonstrate that these pharmaceuticals compouds are promising in modulation of mitochondrial activity in ageing and obesity although more studies are needed to demonstrate their effectivity in mammals and humans.”
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Induction of mitochondrial dysfunction by blocking respiration or knocking down mitochondrial transcription factor A induces insulin resistance in human adipocytes and affects the secretion of adiponectin, attributed to the increase in ROS production by defective mitochondria.
“induction of mitochondrial dysfunction by blocking respiration or knocking down the mitochondrial transcription factor A induce insulin resistance in human adipocytes and affects the secretion of adiponectin in an effect attributed to the increase in ROS production by defective mitochondria (Wang et al., 2013).”
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Physical exercise increases Mfn1 and 2 in human skeletal muscle, indicating the importance of mitochondrial dynamics in the bioenergetic response of mitochondria to energy requirements.
“physical exercise increases Mfn1 and 2 in human skeletal muscle indicating the importance of mitochondrial dynamics in the bioenergetic response of mitochondria to energy requirements (Cartoni et al., 2005).”
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Sesn2 KO mice show glucose intolerance, lower insulin response and development of hepatosteatosis.
“Sesn2 KO mice show glucose intolerance, lower insulin response and development of hepatosteatosis (Lee et al., 2013b; Lee et al., 2012).”
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- cites Lee et al., 2012
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Downregulation of PHB by microRNA27a and 27b resulted in impaired mitochondrial biogenesis and structure integrity, lower activity of complex I and higher ROS production in adipose-derived stem cells.
“downregulation of PHB by microRNA27a and 27b resulted in impaired mitochondrial biogenesis and structure integrity, lower activity of complex I and higher ROS production in adiposederived stem cells (Kang et al., 2013).”
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Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.Deregulation of Pin1 has been implicated in ageing and age-related diseases.
“the deregulation of Pin1 has been also implied in ageing and age-related diseases (Lee et al., 2011).”
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Premisecitation§ Inflammation and lipid accumulation.After recognizing PAMPs or DAMPs, Casp-1 is activated and catalyses transformation of proinflammatory cytokines to their mature forms.
“After recognizing PAMPs or DAMPs, Casp-1 is activated and catalyses the transformation of proinflammatory cytokines to their mature forms (Lupfer and Kanneganti, 2012).”
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Interpretationreasoning§ Inflammation and lipid accumulation.Prolongevity effectors such as CR or resveratrol would reduce NLRP3-inflammasome activation, preventing activation of the vicious cycle.
“Prolongevity effectors such as CR or resveratrol would reduce NLRP3-inflammasome activation preventing the activation of this vicious cycle.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.Deficiency in the capacity of mitochondria to metabolize lipids has been proposed to predispose WAT and skeletal muscle to accumulate lipids and then to the impairment development of insulin resistance.
“The deficiency in the capacity of mitochondria to metabolize lipids has been proposed to predispose WAT and skeletal muscle to accumulate lipids and then, to the impairment development of insulin resistance (Lowell and Shulman, 2005).”
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Premisecitation§ Inflammation and lipid accumulation.Casp-1 activates pathways that precipitate mitochondrial disassembly, increase ROS production and break up the mitochondrial network, triggering a vicious cycle in which mitochondrial dysfunction activates inflammasome and Casp-1 induces mitochondrial dysfunction.
“Casp-1 activates several pathways that precipitate mitochondrial disassembly, increase ROS production and breaks up mitochondrial network, triggering a vicious cycle in which mitochondrial dysfunction activates inflammasome and Casp-1 induces mitochondrial dysfunction (Yu et al., 2014).”
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Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.Other studies performed in rats suggested that insulin resistance is accompanied by an increase in mitochondrial content and an increase in oxidation of lipids.
“other studies performed in rats suggested that insulin resistance is accompanied by an increase in mitochondrial content and an increase in oxidation of lipids (Dela and Helge, 2013; Garcia-Roves et al., 2007; Hancock et al., 2008; Turner et al., 2007).”
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Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.AMPK deficiency results in glucose intolerance, lower physical capacity and obesity.
“deficiency in AMPK results in glucose intolerance, lower physical capacity and obesity; symptoms of metabolic disease (Steinberg et al., 2010).”
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Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.These mitochondrial deficiencies include reduction of fatty acid oxidation, lower expression of genes involved in oxidative activity and decrease of electron transport chain activities.
“These mitochondrial deficiencies include reduction of fatty acid oxidation, lower expression of genes involved in oxidative activity and decrease of electron transport chain activities (Mootha et al., 2003; Patti and Corvera, 2010; Simoneau et al., 1999; Toledo and Goodpaster, 2013).”
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Interpretationreasoning§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.It is probable that the incapacity to control mitochondrial dynamics during ageing, when fat accumulates in WAT, liver or muscle, produces the accumulation of damaged mitochondria and the resulting consequences as metabolism unbalance, insulin resistance or oxidative stress.
“It is probable that the incapacity to control mitochondrial dynamics during ageing, when fat accumulates in WAT, liver or muscle, produces the accumulation of damaged mitochondria and the resulting consequences as metabolism unbalance, insulin resistance or oxidative stress.”
Quote in the paperSubstantial claim- Rests on an assumption: Obesity and T2DM are age-related diseases.
May combine two claims.
Premisecitation§ Metabolic syndrome, fat accumulation and mitochondria.The increase in Pin1 is associated with fat accumulation because Pin1 KO mice have a high-fat-diet-induced obesity-resistant phenotype.
“This increase is associated with the accumulation of fat since in Pin1 KO mice, a high fat diet-induced obesity resistant phenotype has been described (Nakatsu et al., 2015).”
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Interpretationreasoning§ Metabolic syndrome, fat accumulation and mitochondria.Accumulation of fat in muscle probably induces a higher oxidative metabolism based on fatty acids catabolism but this can be accompanied by the increase of mitochondria including damaged and ROS-producing structures that accumulate by deficient mitochondrial turnover and fusion/fission mechanisms.
“Probably, the accumulation of fat in muscle induces a higher oxidative metabolism based on fatty acids catabolism but this can be accompanied by the increase of mitochondria including damaged and ROS-producing structures that accumulate by a deficient mitochondrial turnover and fusion/fission mechanisms.”
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Premisecitation§ Inflammation and lipid accumulation.In patients with diabetes, inhibition of autophagy results in accumulation of dysfunctional mitochondria, leading to higher ROS production and activating inflammasome.
“In patients with diabetes, the inhibition of autophagy results in the accumulation of dysfunctional mitochondria leading to higher ROS production and activating inflammasome (Harijith et al., 2014).”
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Premisecitation§ Mitochondrial dysfunction is associated with age-dependent fat accumulation.Sestrins are regulated by oxidative stress through p53, NRF-2, AP-1 and FOXO and they regulate components that reduce ROS production, increase mitochondrial biogenesis and induce mitophagy, increasing the efficiency of oxidative metabolism in mice.
“sestrins are also regulated by oxidative stress through p53, NRF-2, AP-1 and FOXO and they regulate several components that reduce ROS production, increase mitochondrial biogenesis and induce mitophagy increasing the efficiency of oxidative metabolism in mice (Lee et al., 2013b).”
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Interpretationcitation§ Inflammation and lipid accumulation.Fat accumulation would promote inflammasome-associated SASP that would induce cellular senescence in other tissues, aggravating obesity-dependent chronic inflammation in another vicious cycle.
“fat accumulation would promote inflammasome associated SASP that would induce cellular senescence in other tissues of the organism aggravating by this mechanism the obesity-dependent chronic inflammation in another vicious cycle (Newsholme and de Bittencourt, 2014)”
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Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?Changes in oestrogen levels can modulate genetic expression of mitochondrial factors and be responsible for mitochondrial dysfunction effect in fat accumulation during ageing.
“Changes in oestrogens levels can also modulate the genetic expression of mitochondrial factors and then, be also responsible of mitochondrial dysfunction effect in fat accumulation during ageing (Vasconsuelo et al., 2013).”
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Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?Visceral fat accumulation is associated with many age-related diseases, accompanied by fat accumulation in heart, liver and skeletal muscle, which increases risk for insulin resistance and cardiovascular disease.
“Visceral fat accumulation is associated with many age-related diseases (Huffman and Barzilai, 2009) accompanied by the accumulation of fat in tissues such as the heart, liver and skeletal muscle which increases risk for insulin resistance and cardiovascular disease (Kuk et al., 2009).”
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- cites Kuk et al., 2009
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Premisecitation§ Inflammation and lipid accumulation.SREBPs are activated by hepatitis C virus and induce accumulation of lipid droplets probably by activation of the NLRP3-inflammasome complex.
“These proteins are activated by hepatitis C virus and induce the accumulation of lipid droplets probably by activation of the NLRP3-inflammasome complex (McRae et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites McRae et al., 2015
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- Rests on an assumption: Lipogenesis in liver is modulated by SREBPs.
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Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?In rats, reduction of oestrogens produced decrease of PGC1α expression and reduction of β-oxidation in muscle.
“In rats, a model of menopause by using ovariectomization suggested that reduction of oestrogens produced the decrease of PGC1α expression and the reduction of β-oxidation in muscle (Cavalcanti-de-Albuquerque et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cavalcanti-de-Albuquerque et al., 2014
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Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?These reductions can be prevented by oestrogen replacement therapy, indicating a direct relationship between levels of these hormones and metabolic control and probably mitochondrial activity.
“These reductions can be prevented by oestrogen replacement therapy, indicating a direct relationship between the levels of these hormones and metabolic control and probably mitochondrial activity (Gambacciani et al., 1997).”
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Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?Increase of FSH is responsible for fat accumulation and affects fat redistribution from subcutaneous and abdominal fat to visceral fat.
“the increase of this hormone not only is responsible for fat accumulation but also affects fat redistribution from subcutaneous and abdominal fat to visceral fat, a fact associated with ageing (Zamboni et al., 2005).”
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Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?In MCF-7 cells, mRNA levels of mitochondrial fusion genes increase during estradiol treatment whereas FIS1 gene expression decreases.
“In the human breast cancer cell line MCF-7, the mRNA levels of mitochondrial fusion genes increase during estradiol treatment whereas FIS1 gene expression decreases (Sastre-Serra et al., 2012).”
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Interpretationreasoning§ Inflammation and lipid accumulation.Mitochondria can be at the origin of overactivation of inflammasome in liver and other organs and then of fat accumulation and development of steatohepatitis.
“These studies suggest that mitochondria can be on the origin of the overactivation of inflammasome in liver and other organs and then, accumulation of fat and development of steatohepatitis.”
Quote in the paperSubstantial claim- Rests on an assumption: Activation of different forms of inflammasome is one of the key factors in fat accumulation during ageing.
- Rests on an assumption: Release of danger signals from mitochondria promotes formation of inflammasomes.
May combine two claims.
Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?Low levels of oestrogens decrease PGC1α expression, indicating a putative decrease in mitochondrial biogenesis.
“Low levels of oestrogens decrease PGC1α expression indicating a putative decrease in mitochondrial biogenesis (Cavalcanti-deAlbuquerque et al., 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cavalcanti-de-Albuquerque et al., 2014
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Premisecitation§ Inflammation and lipid accumulation.NLRP3 inflammasome activity is essential in development of high-fat-diet-induced obesity and insulin resistance.
“a NLRP3 KO mice model has demonstrated that the activity of this inflammasome is essential in the development of high-fat dietinduced obesity and in the development of insulin resistance (Stienstra et al., 2011).”
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Premisecitation§ Does fat accumulation and mitochondrial dysfunction depend on sexual hormones?In premenopausal women, oestrogens protect against weight gain by increasing energy expenditure, whereas postmenopausal women gain weight by natural decrease in endogenous estradiol levels.
“In premenopausal women, oestrogens protect against weight gain by increasing energy expenditure, whereas postmenopausal women gain weight by the natural decrease in endogenous estradiol levels (Gambacciani et al., 1997).”
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Interpretationcitation§ Inflammation and lipid accumulation.RSV inhibits NLRP3 activity probably by reducing oxidative stress, increasing mitochondrial turnover and eliminating ROS-producing deficient mitochondria.
“probably by reducing the level of oxidative stress increasing the mitochondrial turnover and eliminating by this mechanism ROS-producing deficient mitochondria (Baur et al., 2006; Tung et al., 2015a).”
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- cites Tung et al., 2015a
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Interpretationreasoning§ Concluding remarks.These two opposite processes probably end in accumulation of damaged mitochondria that increase oxidative damage, contributing to appearance and impairment of insulin resistance, metabolic dysfunction and release of proinflammatory mediators.
“Probably these two opposite processes end in the accumulation of damaged mitochondria that increase oxidative damage that contribute to the appearance and impairment of insulin resistance, metabolic dysfunction and the release of proinflammatory mediators.”
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Interpretationnone given§ Concluding remarks.During ageing a tendency to increase fusion in mitochondria has been reported to maintain mitochondrial activity; however, fat accumulation induces higher activity of fission mechanisms, promoting accumulation of small and less efficient mitochondria.
“During ageing a tendency to increase fusion in mitochondria has been reported in order to maintain mitochondrial activity; however, fat accumulation induces a higher activity of fission mechanisms promoting the accumulation of small and less efficient mitochondria.”
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Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.Activity of these neurons is impaired when the mitochondrial fusion mechanism is altered, producing resistance to fat gain during high fat diet.
“The activity of these neurons is impaired when the mitochondrial fusion mechanism is altered producing resistance to fat gain during high fat diet (Dietrich et al., 2013).”
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Interpretationreasoning§ Concluding remarks.This regulation is affected by sexual hormones that change during ageing, and reduction of oestrogens is probably one of the key factors involved in mitochondrial dysfunction and fat accumulation in humans.
“This regulation is affected by sexual hormones that change during ageing and probably the reduction of oestrogens is one of the key factors involved in mitochondrial dysfunction and fat accumulation in humans.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.Activity of POMC neurons is importantly affected by mitochondrial dynamics.
“It has been suggested that the activity of these neurons is importantly affected by mitochondrial dynamics (Nasrallah and Horvath, 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nasrallah and Horvath, 2014
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Interpretationreasoning§ Concluding remarks.Mitochondrial dysfunction is associated with development of obesity and appearance and progression of age-related diseases.
“Many evidences indicate that mitochondrial dysfunction is associated with the development of obesity and the appearance and progression of age-related diseases (Fig.5).”
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Premisecitation§ Mitochondrial function in POMC neurons and its effect on the control of satiety.Inhibition of mTOR in these neurons caused reduction of food intake and weight loss in old mice, indicating importance of this regulator in satiety control.
“the inhibition of mTOR in these neurons caused reduction of food intake and weight loss in old mice indicating the importance of this regulator in satiety control (Yang et al., 2012).”
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Interpretationnone given§ Concluding remarks.Regulators of metabolism such as mTOR, AMPK and sirtuins are involved in this effect, and the complex equilibrium between their activities modulates mitochondrial biogenesis, dynamics and turnover.
“Regulators of metabolism such as mTOR, AMPK and sirtuins are involved in this effect and the complex equilibrium between their activities modulates mitochondrial biogenesis, dynamics and turnover.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Findings from animal models (mice, rats, worms) about mitochondrial function and fat metabolism can be extrapolated to humans.
“In fact, although no studies have been performed yet in humans, the activity of sestrins has been recently suggested in the effect of exercise to prevent sarcopenia, frailty and obesity in the elderly (Sanchis-Gomar, 2013).”
“This regulation is affected by sexual hormones that change during ageing and probably the reduction of oestrogens is one of the key factors involved in mitochondrial dysfunction and fat accumulation in humans.”
The paper relies on this without support.
Mitochondrial dysfunction is a cause, not merely a consequence, of fat accumulation and insulin resistance.
“It is probable that the incapacity to control mitochondrial dynamics during ageing, when fat accumulates in WAT, liver or muscle, produces the accumulation of damaged mitochondria and the resulting consequences as metabolism unbalance, insulin resistance or oxidative stress.”
“These studies suggest that mitochondria can be on the origin of the overactivation of inflammasome in liver and other organs and then, accumulation of fat and development of steatohepatitis.”
The paper relies on this without support.
Mitochondrial activity in white adipose tissue is associated with fat accumulation.
“Since the regulation of mitochondrial activity in WAT can be associated with the accumulation of fat and a putative disruption of mitochondrial physiology, the study of mitochondrial homeostasis is important to develop strategies or therapies to avoid or delay the progression of fat accumulation-derived diseases.”
The paper relies on this without support.
Modulating mitochondrial homeostasis can prevent or delay fat accumulation-derived diseases.
“the study of mitochondrial homeostasis is important to develop strategies or therapies to avoid or delay the progression of fat accumulation-derived diseases.”
The paper relies on this without support.
Obesity and T2DM are age-related diseases.
“Obesity and T2DM are considered age-related diseases.”
The authors state this as an assumption.
Sestrins expression decays during ageing.
“If sestrins expression decays during ageing, accumulation of damaged mitochondria will increase due to reduction of mito- or autophagy.”
The paper relies on this without support.
No information is available about the activity of sestrins in adipose tissue and its behaviour during ageing.
“However, to date there is no information available about the activity of sestrins in adipose tissue and its behaviour during ageing.”
The paper relies on this without support.
No information is available on whether sestrins affect fat accumulation and modulate mitochondrial activity and turnover during ageing.
“Do sestrins affect fat accumulation and modulate mitochondrial activity and turnover during ageing? No information is available to date.”
The paper relies on this without support.
The bioenergetic state of the cell is directly related with the regulation of mitochondrial dynamics.
“The bioenergetic state of the cell is directly related with the regulation of mitochondrial dynamics, ; the balance in fusion/fission processes occurring in the mitochondrial network.”
The paper relies on this without support.
AMPK is the key component in progression of metabolic syndrome and insulin resistance in WAT.
“Among the regulators of metabolism, AMPK seems to be the key component in the progression of metabolic syndrome and insulin resistance in WAT.”
The paper relies on this without support.
A proinflammatory status accompanies obesity.
“the proinflammatory status that accompanies obesity.”
The paper relies on this without support.
Visceral fat is an important source of proinflammatory cytokines contributing to insulin resistance.
“visceral fat is an important source of proinflammatory cytokines contributing to insulin resistance.”
The paper relies on this without support.
Activation of different forms of inflammasome is one of the key factors in fat accumulation during ageing.
“the activation of different forms of inflammasome is one of the key factors.”
The paper relies on this without support.
Release of danger signals from mitochondria promotes formation of inflammasomes.
“The release of danger signals from mitochondria promotes the formation of inflammasomes.”
The paper relies on this without support.
The cause of gender difference in fat distribution resides in sexual hormones.
“The cause of this difference resides in sexual hormones.”
The paper relies on this without support.
Oestrogens and their receptors favour lipid accumulation in subcutaneous depot in women but visceral fat deposition in men.
“Oestrogens and their receptors favour lipid accumulation in subcutaneous depot in women but visceral fat deposition in men.”
The paper relies on this without support.
Satiety and hunger are controlled by NPY, Agrp and POMC neurons located in the arcuate nucleus of the hypothalamus.
“Satiety and hunger is controlled by neuropeptide-Y (NPY), agouti-related protein (Agrp) and pro-opiomelanocortin (POMC) neurons located in the arcuate nucleus of the hypothalamus.”
The paper relies on this without support.
Both obesity and ageing are associated with rewiring of a principal brain pathway modulating energy homeostasis through promoting reduced activity of satiety POMC neurons.
“Both obesity and ageing are associated with rewiring of a principal brain pathway modulating energy homeostasis through promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons.”
The paper relies on this without support.
Lipogenesis in liver is modulated by SREBPs.
“Lipogenesis in liver is modulated by sterol regulatory element binding proteins (SREBPs).”
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Aging is associated with mitochondrial dysfunction, insulin resistance, oxidative stress, and altered myokine-adipokine signaling, which impair ability to adapt to energetic demands and stressors.
“At the cellular level, aging is associated with mitochondrial dysfunction, insulin resistance, oxidative stress, and altered myokine–adipokine signaling, which collectively impair the body’s ability to adapt to energetic demands and external stressors [2,3].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [3]
The Introduction links mitochondrial dysfunction to functional decline during ageing and reports an association between impaired mitochondrial capacity and insulin resistance. The section “Mitochondrial activity and turnover are affected during ageing” also discusses oxidative stress and damaged mitochondria. Our copy does not establish altered myokine–adipokine signaling or that these factors collectively impair adaptation to energetic demands and external stressors. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Cites
2 retracted
Lokireddy, S., Wijesoma, I. W., Teng, S., Bonala, S., Gluckman, P. D., McFarlane, C., Sharma, M., & Kambadur, R. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.005 · Cited by 154 · cited 10× · see citing works
“Although the ROS-dependent mechanisms involved in the increase of mitochondrial metabolism have to be clarified, it seems that the AMPK-dependent modulation of FoxO-dependent autophagy and PGC1α-regulated mitochondrial biogenesis are involved (Li et al., 2015).”
BackgroundInfluentialRetractedMcRae, S., Iqbal, J., Sarkar-Dutta, M., Lane, S., Nagaraj, A., Ali, N., & Waris, G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.694059 · Cited by 58 · cited 2× · see citing works
“activation of the NLRP3-inflammasome complex (McRae et al., 2015).”
BackgroundRetractedLópez-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · cited 1× · see citing works
“…processes such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intracellular communication (Kennedy et al., 2014; Lopez-Otin et al., 2013).”
BackgroundMootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · cited 2× · see citing works
“Whereas mTORC1 negatively regulates autophagy through phosphorylating the mediators, unc-51-like kinase 1/2 (ULK-1 and ULK-2), in inhibitory sites (Chan, 2009; Kim et al., 2011), AMPK positively regulates autophagy by phosphorylating these proteins in their 10 activating sites (Alers et al., 2012).”
BackgroundTOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602 · cited 1× · see citing works
“AMPK inhibits by phosphorylation several anabolic enzymes such as acetyl-coenzyme A (CoA) carboxylase (ACC), glycerol phosphate acyl transferase (GAPT), 3-hydroxyl-3-methylglutaryl CoA reductase (HMGCR) and glycogen synthase (GS) affecting glycogen and lipid biosynthesis (Hardie et al., 2012).”
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290 · see citing works
Self-citationTSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · cited 2× · see citing works
“But, more importantly, AMPK inhibits mTORC1 activity both directly (Gwinn et al., 2008) or indirectly (Inoki et al., 2003).”
BackgroundAMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849 · see citing works
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082 · cited 2× · see citing works
“Fission segregates components of the network that are irreversibly damaged or unnecessary for subsequent removal (Twig et al., 2008).”
BackgroundGeroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764 · see citing works
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · cited 3× · see citing works
“Importantly, AMPK and SIRT1, the two mainmajor metabolic sensors in cells, modulate directly are direct modulators of PGC1α activity through phosphorylation and deacetylation respectively (Jager et al., 2007; Nemoto et al., 2005).”
BackgroundMitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442 · cited 1× · see citing works
“Mfn2 is also associated in the connection between mitochondria and the endoplasmic reticulum (ER) playing a role in the development of endoplasmic reticulum (ER) stress and fat accumulation in conditions of metabolic stress (de Brito and Scorrano, 2008, 2009).”
BackgroundAssessing mitochondrial dysfunction in cells
Brand, M. D., & Nicholls, D. G. (2011) · Biochemical Journal · doi:10.1042/bj20110162 · Cited by 2,436 · cited 1× · see citing works
“Any abnormality in the key physiological functions of mitochondria: generation of ATP, detoxification of ROS and ROSrelated damage, regulation of cytosolic calcium levels, synthesis of lipids, etc., can be considered as mitochondrial dysfunction (Brand and Nicholls, 2011).”
BackgroundWallace, D. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3365 · Cited by 2,404 · cited 2× · see citing works
“…during ageing (Riera et al., 2016) and, for this reason, it has been associated with a number of age-related diseases such as neurological disorders, cardiovascularCVD, liver and kidney diseases, diabetes and cancer (Lane et al., 2015; Payne and Chinnery, 2015; Ryan et al., 2015; Wallace, 2012).”
BackgroundLaplante, M., & Sabatini, D. (2009) · Journal of Cell Science · doi:10.1242/jcs.051011 · Cited by 2,317 · cited 3× · see citing works
“One of these regulators is the mammalian 5 Target of Rapamycin (mTOR) which is activated by high calorie intake or high levels of aminoacids (Laplante and Sabatini, 2009).”
BackgroundInfluentialMitochondrial dysfunction and type 2 diabetes
Lowell, B. B., & Shulman, G. I. (2005) · Science · doi:10.1126/science.1104343 · Cited by 2,070 · cited 2× · see citing works
“The deficiency in the capacity of mitochondria to metabolize lipids has been proposed to predispose WAT and skeletal muscle to accumulate lipids and then, to the impairment development of insulin resistance (Lowell and Shulman, 2005).”
BackgroundActivation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020 · see citing works
Dynamin-related Protein Drp1 Is Required for Mitochondrial Division in Mammalian Cells
Smirnova, E., Griparić, L., Shurland, D., & van der Bliek, A. M. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.8.2245 · Cited by 1,938 · cited 2× · see citing works
“DRP1 is also a GTPase protein located mainly in the cytosol although a fraction is localized on mitochondria (Smirnova et al., 2001).”
BackgroundLi, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., Park, O., Luo, Z., Lefai, É., Shyy, J. Y.-J., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.009 · Cited by 1,788 · cited 1× · see citing works
“At the same time, AMPK also inhibits the transcriptional activity of sterol regulatory element binding protein (SREBP) decreasing the expression of genes involved in fatty acid synthesis (Li et al., 2011).”
BackgroundRepa, J. J., Liang, G., Ou, J., Bashmakov, Y. K., Lobaccaro, J. A., Shimomura, I., Shan, B., Brown, M. S., Goldstein, J. L., & Mangelsdorf, D. J. (2000) · Genes & Development · doi:10.1101/gad.844900 · Cited by 1,693 · cited 1× · see citing works
“LXRα induces the expression of fatty acid synthesis (FAS), acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c) (Grefhorst et al., 2002; Repa et al., 2000).”
BackgroundRole of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks
Alers, S., Löffler, A. S., Wesselborg, S., & Stork, B. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06159-11 · Cited by 1,483 · cited 2× · see citing works
“In a similar response that women, testosterone therapy prevents the gain in visceral fat in non-obese ageing men (Allan et al., 2008).”
BackgroundDisruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction
Chen, H., Chomyn, A., & Chan, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503062200 · Cited by 1,376 · cited 3× · see citing works
“Further, RNAi studies have demonstrated an inverse relationship between fusion capacity and respiration rates mainly affecting complexes I, III and IV in mammals and humans (Chen et al., 2005).”
BackgroundDecline in skeletal muscle mitochondrial function with aging in humans
Short, K. R., Bigelow, M. L., Kahl, J., Singh, R., Coenen-Schimke, J., Raghavakaimal, S., & Nair, K. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501559102 · Cited by 1,333 · cited 1× · see citing works
“Another factor involved in the decay in mitochondrial turnover during ageing is the impairment of mitochondrial biogenesis, especially in high energy demanding tissues such as muscle, brain or heart (Conley et al., 2000; Short et al., 2005).”
p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling
Budanov, A. V., & Karin, M. (2008) · Cell · doi:10.1016/j.cell.2008.06.028 · Cited by 1,326 · cited 2× · see citing works
“Sestrins are another highly conserved protein family encoded by genes known as Sens that are upregulated after environmental stress, hypoxia and DNA damage (Budanov and Karin, 2008).”
BackgroundCalorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation
Qiu, X., Brown, K., Hirschey, M. D., Verdin, E., & Chen, D. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.015 · Cited by 1,310 · cited 1× · see citing works
“SIRT3 has been also involved in the regulation by deacetylation of electron transport chain complex II activity (Kendrick et al., 2011), modulation of the activity of Mn-SOD (Qiu et al., 2010) or regulation of autophagy by deacetylation of FOXO3 (Kume et al., 2010).”
BackgroundMitochondrial Dynamics and Metabolic Regulation
Wai, T., & Langer, T. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.12.001 · Cited by 1,304 · cited 11× · see citing works
“Mitofusins are located at the outer membrane of mitochondria acting in the fusion of these membranes whereas OPA1 is located in the intermembrane space and acts in the fusion of the inner membranes.”
BackgroundInfluentialAnderson, E. J., Lustig, M. E., Boyle, K. E., Woodlief, T. L., Kane, D. A., Lin, C.-T., Price, J. W., Kang, L., Rabinovitch, P. S., Szeto, H. H., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37048 · Cited by 1,253 · cited 2× · see citing works
“fed conditions show higher H2O2-mitochondrial production affecting the redox state of the cells but without changes in the mitochondrial respiratory function (Anderson et al., 2009).”
BackgroundFis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission
Losón, O. C., Song, Z., Chen, H., & Chan, D. C. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-10-0721 · Cited by 1,235 · cited 12× · see citing works
“DRP1 is recruited on the outer mitochondrial membrane by FIS1 which is already inserted in this membrane (Santel and Frank, 2008; Yoon et al., 2003).”
BackgroundInfluentialCalorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107 · cited 2× · see citing works
“Further, it has been demonstrated that eNOS is induced by CR in mice and human muscle (Civitarese et al., 2007; Nisoli et al., 2005) being essential in the CR-induced mitochondrial biogenesis since in eNOS-/- mice this induction is blocked (Nisoli et al., 2005).”
BackgroundHandschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090 · cited 2× · see citing works
“8 The peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) is the central factor involved in the regulation of mitochondrial mass and the adaptation to energy demand since this transcriptional coactivator stimulates mitochondrial biogenesis, regulates mitochondrial dynamics, modulates oxidative phos…”
BackgroundSIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α
Nemoto, S., Fergusson, M. M., & Finkel, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501485200 · Cited by 1,047 · cited 2× · see citing works
“Importantly, AMPK and SIRT1, the two mainmajor metabolic sensors in cells, modulate directly are direct modulators of PGC1α activity through phosphorylation and deacetylation respectively (Jager et al., 2007; Nemoto et al., 2005).”
BackgroundOxidation events and skin aging
Kammeyer, A., & Luiten, R. M. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.001 · Cited by 980 · cited 2× · see citing works
“…most data suggest that there is an increase in oxidative damage in the elderly affecting senescence (Lu and Finkel, 2008), fertility declining (Benkhalifa et al., 2014), skin ageing (Kammeyer and Luiten, 2015), neutrophils’ activity (Kovalenko et al., 2014) or skeletal muscle (McDonagh, 2016).”
BackgroundMitochondrial Dynamics in Mammalian Health and Disease
Liesa, M., Palacín, M., & Zorzano, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00030.2008 · Cited by 953 · see citing works
The sexual dimorphism of obesity
Palmer, B. F., & Clegg, D. J. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.11.029 · Cited by 919 · cited 3× · see citing works
“In humans, fat deposits depend on the gender of the individual (Palmer and Clegg, 2015).”
BackgroundInfluentialMattagajasingh, I., Kim, C.-S., Naqvi, A., Yamamori, T., Hoffman, T. A., Jung, S.-B., DeRicco, J., Kasuno, K., & Irani, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704329104 · Cited by 881 · cited 1× · see citing works
“For example, SIRT1 has been suggested to play an important role since this enzyme activates eNOS by deacetylation in human vascular cells (Mattagajasingh et al., 2007).”
BackgroundMitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism
Bach, D., Pich, S., Soriano, F. X., Vega, N., Baumgartner, B., Oriola, J., Daugaard, J. R., Lloberas, J., Camps, M., Zierath, J. R., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212754200 · Cited by 832 · cited 6× · see citing works
“Mfn2 depleted rat muscle cells show a reduced proton leak and lower bioenergetics efficiency 22 indicated by lower glucose oxidation and mitochondrial respiration (Bach et al., 2003).”
BackgroundInfluentialYoon, Y., Krueger, E. W., Oswald, B. J., & McNiven, M. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5409-5420.2003 · Cited by 820 · cited 2× · see citing works
“…accumulation of giant dysfunctional mitochondria characterized by highly interconnected networks and ultrastructural abnormalities in human lymphocytes and mice cells (Beregi and Regius, 1987) accompanied by higher production of ROS and lower mitochondrial respiratory activity (Yoon et al., 2006).”
BackgroundCalorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790 · cited 2× · see citing works
“Further, it has been demonstrated that eNOS is induced by CR in mice and human muscle (Civitarese et al., 2007; Nisoli et al., 2005) being essential in the CR-induced mitochondrial biogenesis since in eNOS-/- mice this induction is blocked (Nisoli et al., 2005).”
BackgroundMitonuclear communication in homeostasis and stress
Quirós, P. M., Mottis, A., & Auwerx, J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.23 · Cited by 787 · cited 1× · see citing works
“Defects in mitochondrial activity activate a retrograde response that communicat mitochondrial dysfunction to nucleus through activation of AMPK/PGC1α signalling axis (Quiros et al., 2016).”
BackgroundJoseph, S. B., Laffitte, B. A., Patel, P. H., Watson, M. A., Matsukuma, K. E., Walczak, R., Collins, J. L., Osborne, T. F., & Tontonoz, P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111041200 · Cited by 779 · see citing works
Age-related changes in total and regional fat distribution
Kuk, J. L., Saunders, T. J., Davidson, L. E., & Ross, R. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.06.001 · Cited by 778 · cited 2× · see citing works
“Visceral fat accumulation is associated with many age-related diseases (Huffman and Barzilai, 2009) accompanied by the accumulation of fat in tissues such as the heart, liver and skeletal muscle which increases risk for insulin resistance and cardiovascular disease (Kuk et al., 2009).”
BackgroundInflammasome is a central player in the induction of obesity and insulin resistance
Stienstra, R., van Diepen, J. A., Tack, C. J., Zaki, M. H., van de Veerdonk, F. L., Perera, D., Neale, G. A., Hooiveld, G. J., Hijmans, A., Vroegrijk, I., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100255108 · Cited by 727 · cited 1× · see citing works
“Furthermore, a NLRP3 KO mice model has demonstrated that the activity of this inflammasome is essential in the development of high-fat dietinduced obesity and in the development of insulin resistance (Stienstra et al., 2011).”
BackgroundLee, C., Zeng, J., Drew, B. G., Sallam, T., Martin-Montalvo, A., Wan, J., Kim, S.-J., Mehta, H., Hevener, A. L., de Cabo, R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.02.009 · Cited by 715 · cited 1× · see citing works
“Interestingly, treatment with MOTS-C in mice prevent agedependent and high-fat diet induced insulin resistance and obesity indicating an important role of mitochondria in the control of fat metabolism probably producing prolongevity effects (Fuku et al., 2015; Lee et al., 2015).”
BackgroundOxidative capacity and ageing in human muscle
Conley, K. E., Jubrias, S. A., & Esselman, P. C. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00203.x · Cited by 651 · see citing works
Jheng, H.-F., Tsai, P.-J., Guo, S.-M., Kuo, L.-H., Chang, C.-S., Su, I.-J., Chang, C.-R., & Tsai, Y.-S. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05603-11 · Cited by 650 · cited 3× · see citing works
“On the other hand, higher mitochondrial fission has been also associated with fat accumulation in genetically induced obesity (ob/ob) mice or in high-fat induced obesity (Jheng et al., 2012) and with insulin resistance in the same mice model (Holmstrom et al., 2012).”
BackgroundHealth consequences of obesity in the elderly: a review of four unresolved questions
Zamboni, M. M., Mazzali, G., Zoico, E., Harris, T. B., Meigs, J. B., Francesco, V. D., Fantin, F., Bissoli, L., & Bosello, O. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0803005 · Cited by 649 · cited 2× · see citing works
“redistribution from subcutaneous and abdominal fat to visceral fat, a fact associated with ageing (Zamboni et al., 2005).”
BackgroundKume, S., Uzu, T., Horiike, K., Chin-Kanasaki, M., Isshiki, K., Araki, S.-I., Sugimoto, T., Haneda, M., Kashiwagi, A., & Koya, D. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41376 · Cited by 640 · cited 1× · see citing works
“SIRT3 has been also involved in the regulation by deacetylation of electron transport chain complex II activity (Kendrick et al., 2011), modulation of the activity of Mn-SOD (Qiu et al., 2010) or regulation of autophagy by deacetylation of FOXO3 (Kume et al., 2010).”
BackgroundMitochondria are morphologically and functionally heterogeneous within cells
Collins, T. J., Berridge, M. J., Lipp, P., & Bootman, M. D. (2002) · The EMBO Journal · doi:10.1093/emboj/21.7.1616 · Cited by 588 · cited 2× · see citing works
“Unfortunately the factors that control the change in mitochondrial dynamics during ageing have not been determined yet (Collins et al., 2002).”
BackgroundSestrin as a feedback inhibitor of TOR that prevents age-related pathologies
Lee, J. H., Budanov, A. V., Park, E. J., Birse, R., Kim, T. E., Perkins, G. A., Ocorr, K., Ellisman, M. H., Bodmer, R., Bier, E., et al. (2010) · Science · doi:10.1126/science.1182228 · Cited by 570 · see citing works
The role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551 · cited 2× · see citing works
“Thus, mitochondrial dysfunction has been described in the main organs involved in the development of metabolic syndrome during ageing such as muscle, liver and adipose tissue (Patti and Corvera, 2010).”
BackgroundChen, G., Liang, G., Ou, J., Goldstein, J. L., & Brown, M. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404297101 · Cited by 546 · cited 2× · see citing works
“LXRα is a transcription factor that modulates lipid synthesis in liver (Joseph et al., 2002) and regulates insulin-stimulated lipogenesis (Chen et al., 2004).”
BackgroundHigh-fat diets cause insulin resistance despite an increase in muscle mitochondria
Hancock, C. R., Han, D.-H., Chen, M., Terada, S., Yasuda, T., Wright, D. C., & Holloszy, J. O. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802057105 · Cited by 538 · see citing works
Emerging functions of mammalian mitochondrial fusion and fission
Chen, H., & Chan, D. C. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi270 · Cited by 538 · cited 2× · see citing works
“Placenta, skeletal muscle, vascular smooth cells and neurons suffer mitochondrial defects by deficiencies in mitochondrial dynamics (Chen and Chan, 2005).”
BackgroundMitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease
Ryan, B. J., Hoek, S., Fon, E. A., & Wade-Martins, R. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.02.003 · Cited by 524 · see citing works
Excess Lipid Availability Increases Mitochondrial Fatty Acid Oxidative Capacity in Muscle
Turner, N., Bruce, C. R., Beale, S. M., Hoehn, K. L., So, T., Rolph, M. S., & Cooney, G. J. (2007) · Diabetes · doi:10.2337/db07-0093 · Cited by 520 · cited 2× · see citing works
“However, other studies performed in rats suggested that insulin resistance is accompanied by an increase in mitochondrial content and an increase in oxidation of lipids (Dela and Helge, 2013; Garcia-Roves et al., 2007; Hancock et al., 2008; Turner et al., 2007).”
BackgroundMitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance
Schneeberger, M., Dietrich, M. O., Sebastián, D., Imbernón, M., Castaño, C., Garcia, A., Esteban, Y., Gonzalez-Franquesa, A., Rodríguez, I. C., Bortolozzi, A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.003 · Cited by 519 · see citing works
Larson-Meyer, D. E., Heilbronn, L. K., Redman, L. M., Newcomer, B. R., Frisard, M. I., Anton, S., Smith, S. R., Alfonso, A., Ravussin, E., & the Pennington CALERIE Team (2006) · Diabetes Care · doi:10.2337/dc05-2565 · Cited by 504 · see citing works
Grefhorst, A., Elzinga, B. M., Voshol, P. J., Plösch, T., Kok, T., Bloks, V. W., van der Sluijs, F. H., Havekes, L. M., Romijn, J. A., Verkade, H. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204887200 · Cited by 502 · cited 2× · see citing works
“sterol regulatory element binding protein 1c (SREBP-1c) (Grefhorst et al., 2002; Repa et al., 2000).”
BackgroundRattan, S. I. S. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2007.03.002 · Cited by 498 · cited 1× · see citing works
“Due to the dual role of ROS as damaging and signalling factors, a moderate level of ROS production during life can be beneficial by inducing hormetic responses that reinforce the capacity of the organism to respond to stronger injury (Rattan, 2008).”
BackgroundMitochondrial Aging and Age-Related Dysfunction of Mitochondria
Chistiakov, D. A., Sobenin, I. A., Revin, V. V., Orekhov, A. N., & Bobryshev, Y. V. (2014) · BioMed Research International · doi:10.1155/2014/238463 · Cited by 497 · see citing works
Bae, S. H., Sung, S. H., Oh, S. Y., Lim, J. M., Lee, S. K., Park, Y. N., Lee, H. E., Kang, D., & Rhee, S. G. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.002 · Cited by 492 · cited 3× · see citing works
“24 Regarding sestrins, transgenic mice deficient in Sens2 and Sens3 genes have demonstrated the important role of these proteins in the suppression of age and obesity-associated mitochondrial disorders (Bae et al., 2013; Lee et al., 2012).”
BackgroundSimoneau, J., Veerkamp, J. H., Turcotte, L. P., & Kelley, D. E. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.14.2051 · Cited by 491 · see citing works
Andropause: clinical implications of the decline in serum testosterone levels with aging in men
Matsumoto, A. M. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.2.m76 · Cited by 490 · cited 2× · see citing works
“A tendency towards higher visceral adiposity associated with a greater morbidity due to the increase of risk for cardiovascular disease (CVD), hypertension and T2DM is has been associated with the progression of ageing (Matsumoto, 2002).”
BackgroundDiet and exercise signals regulate SIRT3 and activate AMPK and PGC-1α in skeletal muscle
Palacios, O. M., Carmona, J. J., Michan, S., Chen, K. Y., Manabe, Y., III, J. L. W., Goodyear, L. J., & Tong, Q. (2009) · Aging · doi:10.18632/aging.100075 · Cited by 487 · cited 3× · see citing works
“Furthermore, SIRT3 KO mice show repression of PGC1α down regulation and low levels of AMPK phosphorylation after CR indicating a key 9 role of this mitochondrial sirtuin in metabolic adaptation to calorie intake (Palacios et al., 2009).”
BackgroundInfluentialAMPK at the Nexus of Energetics and Aging
Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483 · see citing works
Reactive oxygen species at the crossroads of inflammasome and inflammation
Harijith, A. K., Ebenezer, D. L., & Natarajan, V. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00352 · Cited by 474 · cited 1× · see citing works
“In patients with diabetes, the inhibition of autophagy results in the accumulation of dysfunctional mitochondria leading to higher ROS production and activating inflammasome (Harijith et al., 2014).”
BackgroundCalorie restriction and sirtuins revisited
Guarente, L. (2013) · Genes & Development · doi:10.1101/gad.227439.113 · Cited by 464 · cited 2× · see citing works
“However, the most studied aspect of Sirtuins has been their role in longevity (Guarente, 2011, 2013).”
BackgroundPich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., & Zorzano, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi149 · Cited by 455 · see citing works
Inflammasome activation leads to Caspase-1–dependent mitochondrial damage and block of mitophagy
Yu, J.-J., Nagasu, H., Murakami, T., Hoang, H., Broderick, L., Hoffman, H., & Horng, T. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1414859111 · Cited by 449 · cited 1× · see citing works
“…other hand, Casp-1 activates several pathways that precipitate mitochondrial disassembly, increase ROS production and breaks up mitochondrial network, triggering a vicious cycle in which mitochondrial dysfunction activates inflammasome and Casp-1 induces mitochondrial dysfunction (Yu et al., 2014).”
BackgroundSIRT3 Deacetylates and Activates OPA1 To Regulate Mitochondrial Dynamics during Stress
Samant, S. A., Zhang, H. J., Hong, Z., Pillai, V. B., Sundaresan, N. R., Wolfgeher, D., Archer, S. L., Chan, D. C., & Gupta, M. P. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01483-13 · Cited by 446 · see citing works
Unraveling the Truth About Antioxidants: Mitohormesis explains ROS-induced health benefits
Ristow, M. (2014) · Nature Medicine · doi:10.1038/nm.3624 · Cited by 417 · see citing works
Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise
Cartoni, R., Léger, B., Hock, M. B., Praz, M., Crettenand, A., Pich, S., Ziltener, J., Luthi, F., Dériaz, O., Zorzano, A., et al. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.092031 · Cited by 406 · cited 3× · see citing works
“…conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are 21 associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans (Cartoni et al., 2005; Dolinsky et al., 2013; Soriano et al., 2006).”
BackgroundMitochondria: diversity in the regulation of the NLRP3 inflammasome
Gurung, P., Lukens, J. R., & Kanneganti, T.-D. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.11.008 · Cited by 393 · cited 5× · see citing works
“In several of the models studied including rodents and humans, these diseases are associated with mitochondrial dysfunction indicated by low expression of mtDNA and reduction of the levels of proteins involved in oxidative phosphorylation (OXPHOS).”
BackgroundInfluentialTen years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases
Imai, S., & Guarente, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.02.003 · Cited by 387 · cited 2× · see citing works
“In mammals, CR induces the expression and the activity of sirtuins in many organs and their activities have been associated with most of the metabolic effects produced by CR (Imai and Guarente, 2010).”
BackgroundFatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation
Kendrick, A. A., Choudhury, M., Rahman, S. M., McCurdy, C. E., Friederich, M., Van Hove, J. L. K., Watson, P. A., Birdsey, N., Bao, J., Gius, D., et al. (2011) · Biochemical Journal · doi:10.1042/bj20100791 · Cited by 382 · see citing works
Sensing of energy and nutrients by AMP-activated protein kinase
Hardie, D. G. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001925 · Cited by 372 · cited 3× · see citing works
“This kinase is activated in response to the increase of the AMP/ATP ratio, for example, after deprivation of glucose, whereas its activity is reduced when cells are full of energy and the AMP/ATP ratio decreases (Hardie, 2011).”
BackgroundInfluentialMitochondrial ROS produced via reverse electron transport extend animal lifespan
Scialò, F., Sriram, A., Fernández-Ayala, D., Gubina, N., Lõhmus, M., Nelson, G., Logan, A., Cooper, H. M., Navas, P., Enríquez, J. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.009 · Cited by 371 · cited 5× · see citing works
“…study in Drosophila indicates that ROS increase with age as mitochondrial function deteriorates but high levels of ROS during the life of the organism seems to act as secondary messengers inducing endogenous protective mechanisms in the animals that can increase lifespan (Scialo et al., 2016).”
BackgroundInfluentialExpression of <i>Mfn2</i>, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle
Bach, D., Naon, D., Pich, S., Soriano, F. X., Vega, N., Rieusset, J., Laville, M., Guillet, C., Boirie, Y., Wallberg-Henriksson, H., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2685 · Cited by 369 · see citing works
Mitochondrial biogenesis and healthy aging
López-Lluch, G., Irusta, P. M., Navas, P., & de Cabo, R. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.06.014 · Cited by 364 · cited 4× · see citing works
“Renovation of the mitochondrial network plays a key role in health-span increase after CR (Lopez-Lluch et al., 2008) indicating that the control of the accumulation of damaged mitochondria is an important factor in the progression of ageing.”
BackgroundInfluentialMitochondrial effectors of cellular senescence: beyond the free radical theory of aging
Ziegler, D. V., Wiley, C. D., & Velarde, M. C. (2014) · Aging Cell · doi:10.1111/acel.12287 · Cited by 353 · cited 3× · see citing works
“…defects in mitochondrial fusion/fission dynamics are also essential for the quality control of mitochondria in many age-related diseases as in the case of cardiac homeostasis and senescence (Biala et al., 2015), or in neurodegeneration and hypothalamic dysfunction (Zorzano and Claret, 2015).”
BackgroundSoriano, F. X., Liesa, M., Bach, D., Chan, D. C., Palacín, M., & Zorzano, A. (2006) · Diabetes · doi:10.2337/db05-0509 · Cited by 343 · cited 2× · see citing works
“…conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are 21 associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans (Cartoni et al., 2005; Dolinsky et al., 2013; Soriano et al., 2006).”
BackgroundSestrins Orchestrate Cellular Metabolism to Attenuate Aging
Lee, J. H., Budanov, A. V., & Karin, M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.018 · Cited by 339 · see citing works
Adipogenesis and aging: does aging make fat go MAD
Kirkland, J. L., Tchkonia, T., Pirtskhalava, T., Han, J., & Karagiannides, I. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00014-1 · Cited by 339 · cited 1× · see citing works
“Interestingly, in these cases a transient increase in oxidative capacity was found in human liver at the same time that oxidative stress increases (Koliaki and Roden, 2016).”
BackgroundMitochondrial dysfunction in aging: Much progress but many unresolved questions
Payne, B. A. I., & Chinnery, P. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.022 · Cited by 335 · cited 4× · see citing works
“…of mitochondria as the mainmajor source of intracellular ROS production in ageing has been questioned during the last 11 years (Gram et al., 2015; Payne and Chinnery, 2015), most data suggest that there is an increase in oxidative damage in the elderly affecting senescence (Lu and Finkel, 2008),…”
BackgroundInfluentialGoncalves, R. L. S., Quinlan, C. L., Perevoshchikova, I. V., Hey-Mogensen, M., & Brand, M. D. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.619072 · Cited by 329 · see citing works
Lu, T., & Finkel, T. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.011 · Cited by 327 · cited 3× · see citing works
“…et al., 2015; Payne and Chinnery, 2015), most data suggest that there is an increase in oxidative damage in the elderly affecting senescence (Lu and Finkel, 2008), fertility declining (Benkhalifa et al., 2014), skin ageing (Kammeyer 11 and Luiten, 2015), neutrophils’ activity (Kovalenko et al.,…”
BackgroundInfluentialBody weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women
Gambacciani, M., Ciaponi, M., Cappagli, B., Piaggesi, L., De Simone, L., Orlandi, R., & Genazzani, A. R. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.2.3735 · Cited by 321 · see citing works
Of mice and men: the benefits of caloric restriction, exercise, and mimetics
Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.11.005 · Cited by 318 · cited 1× · see citing works
“Prolongevity CR mimetics such as rapamycin and metformin have also been proposed to modulate mitochondrial dynamics in obesity and age-related diseases (Mercken et al., 2012).”
BackgroundAging in adipocytes: Potential impact of inherent, depot-specific mechanisms
CARTWRIGHT, M., TCHKONIA, T., & KIRKLAND, J. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.03.003 · Cited by 318 · see citing works
Dietrich, M. O., Liu, Z.-W., & Horvath, T. L. (2013) · Cell · doi:10.1016/j.cell.2013.09.004 · Cited by 306 · cited 2× · see citing works
“The activity of these neurons is impaired when the mitochondrial fusion mechanism is altered producing resistance to fat gain during high fat diet (Dietrich et al., 2013).”
BackgroundMolecular mechanisms linking calorie restriction and longevity
Merry, B. J. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00038-9 · Cited by 304 · see citing works
Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence
Lee, S., Jeong, S.-Y., Lim, W.-C., Kim, S., Park, Y.-Y., Sun, X., Youle, R. J., & Cho, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700679200 · Cited by 298 · cited 2× · see citing works
“Blocking the fission process by depleting FIS1 or blocking DRP1 activity leads to cell senescence in human cells accompanied by the accumulation of damaged mitochondria showing lower mitochondrial potential and higher ROS production (Lee et al., 2007; Park et al., 2010).”
BackgroundAllan, C. A., Strauss, B. J. G., Burger, H. G., Forbes, E. A., & McLachlan, R. I. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1291 · Cited by 298 · cited 2× · see citing works
“therapy in men prevents the gain in visceral fat in non-obese ageing men (Allan et al., 2008).”
BackgroundMaintenance of metabolic homeostasis by Sestrin2 and Sestrin3
Lee, J. H., Budanov, A. V., Talukdar, S., Park, E. J., Park, H. L., Park, H.-W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.004 · Cited by 295 · cited 7× · see citing works
“24 Regarding sestrins, transgenic mice deficient in Sens2 and Sens3 genes have demonstrated the important role of these proteins in the suppression of age and obesity-associated mitochondrial disorders (Bae et al., 2013; Lee et al., 2012).”
BackgroundInfluentialAge, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function
Karakelides, H., Irving, B. A., Short, K. R., O'Brien, P., & Nair, K. S. (2010) · Diabetes · doi:10.2337/db09-0591 · Cited by 293 · cited 3× · see citing works
“Thus, the prevalence of obesity in older people has been considered the major cause of metabolic syndrome (Karakelides et al., 2010) and changes in adipose tissue have been recently associated with the development of T2DM (Abranches et al.”
BackgroundInfluentialCalorie restriction as an intervention in ageing
López‐Lluch, G., & Navas, P. (2015) · The Journal of Physiology · doi:10.1113/jp270543 · Cited by 291 · cited 2× · see citing works
“In fact, prolongevity factors such as CR, exercise and polyphenols prevent the accumulation of damaged mitochondria at least in part by inducing mito- and autophagy (Lopez-Lluch and Navas, 2015) (LopezLluch and Navas, 2016) (Fig.”
BackgroundSelf-citationStorlien, L., Oakes, N. D., & Kelley, D. E. (2004) · Proceedings of the Nutrition Society · doi:10.1079/pns2004349 · Cited by 291 · cited 3× · see citing works
“This impairment is known as “metabolic inflexibility” (Griffin et al., 2015), that is present in obese people since they are able to oxidize lipids in insulin-stimulated conditions instead to metabolize glucose being mitochondria the key organelles affecting this incapacity (Storlien et al., 2004).”
BackgroundHumanin: a harbinger of mitochondrial-derived peptides
Lee, C., Yen, K., & Cohen, P. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.01.005 · Cited by 284 · cited 7× · see citing works
“Interestingly, sestrins are also regulated by oxidative stress through p53, NRF-2, AP-1 and FOXO and they regulate several components that reduce ROS production, increase mitochondrial biogenesis and induce mitophagy increasing the efficiency of oxidative metabolism in mice (Lee et al., 2013b).”
BackgroundInfluentialYoon, Y., Yoon, D., Lim, I. K., Yoon, S., Chung, H., Rojo, M., Malka, F., Jou, M., Martinou, J., & Yoon, G. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20753 · Cited by 275 · cited 1× · see citing works
“…accumulation of giant dysfunctional mitochondria characterized by highly interconnected networks and ultrastructural abnormalities in human lymphocytes and mice cells (Beregi and Regius, 1987) accompanied by higher production of ROS and lower mitochondrial respiratory activity (Yoon et al., 2006).”
BackgroundMai, S., Klinkenberg, M., Auburger, G., Bereiter-Hahn, J., & Jendrach, M. (2010) · Journal of Cell Science · doi:10.1242/jcs.059246 · Cited by 256 · cited 3× · see citing works
“production by mitochondrial dysfunction (Mai et al., 2010) or even a defensive response to maintain functional cell mitochondria (Chen and Chan, 2005).”
BackgroundGarcia-Roves, P., Huss, J. M., Han, D.-H., Hancock, C. R., Iglesias-Gutierrez, E., Chen, M., & Holloszy, J. O. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704024104 · Cited by 246 · cited 3× · see citing works
“Thus, a progressive deterioration of supercomplexes in during ageing could be 12 the cause of an irreversible increase in ROS during ageingin older organisms (Genova and Lenaz, 2015).”
BackgroundReconsidering the Role of Mitochondria in Aging
Gonzalez-Freire, M., de Cabo, R., Bernier, M., Sollott, S. J., Fabbri, E., Navas, P., & Ferrucci, L. (2015) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glv070 · Cited by 244 · cited 1× · see citing works
“Mitochondria play a key role in the pathophysiology of ageing and in earlier stages of the events leading to the ageing phenotype (Gonzalez-Freire et al., 2015).”
BackgroundPark, Y.-Y., Lee, S., Karbowski, M., Neutzner, A., Youle, R. J., & Cho, H. (2010) · Journal of Cell Science · doi:10.1242/jcs.061481 · Cited by 244 · cited 2× · see citing works
“Blocking the fission process by depleting FIS1 or blocking DRP1 activity leads to cell senescence in human cells accompanied by the accumulation of damaged mitochondria showing lower mitochondrial potential and higher ROS production (Lee et al., 2007; Park et al., 2010).”
BackgroundYang, S.-B., Tien, A.-C., Boddupalli, G., Xu, A. W., Jan, Y. N., & Jan, L. Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.043 · Cited by 242 · cited 2× · see citing works
“On the contrary, the inhibition of mTOR in these neurons caused reduction of food intake and weight loss in old mice indicating the importance of this regulator in satiety control (Yang et al., 2012).”
BackgroundHigh levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy
Gomes, L. C., & Scorrano, L. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.05.442 · Cited by 239 · cited 2× · see citing works
“the importance of a functional fission machinery to discard damaged mitochondria by autophagy or mitophagy (Gomes and Scorrano, 2008; Twig et al., 2008).”
BackgroundRole of visceral adipose tissue in aging
Huffman, D. M., & Barzilai, N. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.01.008 · Cited by 220 · cited 2× · see citing works
“Visceral fat accumulation is associated with many age-related diseases (Huffman and Barzilai, 2009) accompanied by the accumulation of fat in tissues such as the heart, liver and skeletal muscle which increases risk for insulin resistance and cardiovascular disease (Kuk et al., 2009).”
BackgroundmTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex
Chan, E. Y. (2009) · Science Signaling · doi:10.1126/scisignal.284pe51 · Cited by 214 · cited 2× · see citing works
“Whereas mTORC1 negatively regulates autophagy through phosphorylating the mediators, unc-51-like kinase 1/2 (ULK-1 and ULK-2), in inhibitory sites (Chan, 2009; Kim et al., 2011), AMPK positively regulates autophagy by phosphorylating these proteins in their 10 activating sites (Alers et al., 2012).”
BackgroundRole of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes
Zorzano, A., Liesa, M., & Palacín, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.02.004 · Cited by 209 · cited 3× · see citing works
“particular in Mfn2, have been associated with a reduced mitochondrial function in skeletal muscle in obesity and T2DM (Zorzano et al., 2009) and recently aberrant mitochondrial fission has been also associated with insulin resistance in mouse skeletal muscle (Jheng et al.”
BackgroundInfluentialMutations in Fis1 disrupt orderly disposal of defective mitochondria
Shen, Q., Yamano, K., Head, B. P., Kawajiri, S., Cheung, J. T. M., Wang, C., Cho, J.-H., Hattori, N., Youle, R. J., & van der Bliek, A. M. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-09-0525 · Cited by 209 · see citing works
The role of mitochondrial dysfunction in age-related diseases
Lane, R. K., Hilsabeck, T., & Rea, S. L. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.021 · Cited by 205 · cited 2× · see citing works
“…during ageing (Riera et al., 2016) and, for this reason, it has been associated with a number of age-related diseases such as neurological disorders, cardiovascularCVD, liver and kidney diseases, diabetes and cancer (Lane et al., 2015; Payne and Chinnery, 2015; Ryan et al., 2015; Wallace, 2012).”
BackgroundSirtuins, Aging, and MetabolismPreprint
Guarente, L. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010629 · Cited by 205 · cited 2× · see citing works
“However, the most studied aspect of Sirtuins has been their role in longevity (Guarente, 2011, 2013).”
BackgroundProhibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans
Artal-Sanz, M., & Tavernarakis, N. (2009) · Nature · doi:10.1038/nature08466 · Cited by 196 · cited 2× · see citing works
“Prohibitins are ubiquitous, evolutionary conserved proteins that form a ring-like complex at the inner membrane of the mitochondria (Artal-Sanz and Tavernarakis, 2009).”
BackgroundSestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury
Ishihara, M., Urushido, M., Hamada, K., Matsumoto, T., Shimamura, Y., Ogata, K., Inoue, K., Taniguchi, Y., Horino, T., Fujieda, M., et al. (2013) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00642.2012 · Cited by 195 · cited 5× · see citing works
“On the other hand, other studies carried out in rats proposed that sestrins-dependent mTORC1 inactivation through AMPK induction is critical in the maintenance of autophagy and, then, the elimination of dysfunctional mitochondria (Ishihara et al., 2013).”
BackgroundInfluentialDiet impact on mitochondrial bioenergetics and dynamics
Putti, R., Sica, R., Migliaccio, V., & Lionetti, L. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00109 · Cited by 192 · cited 3× · see citing works
“These dysfunctions have beenhave been regulated modulated by CR and exercise (Putti et al., 2015).”
BackgroundInfluentialPeptidyl-prolyl cis–trans isomerase Pin1 in ageing, cancer and Alzheimer disease
Lee, T. H., Pastorino, L., & Lu, K. P. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411001906 · Cited by 181 · cited 1× · see citing works
“Interestingly, the deregulation of Pin1 has been also implied in ageing and age-related diseases (Lee et al., 2011).”
BackgroundSreekumar, P. G., Ishikawa, K., Spee, C., Mehta, H. H., Wan, J., Yen, K., Cohen, P., Kannan, R., & Hinton, D. R. (2016) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.15-17053 · Cited by 179 · cited 1× · see citing works
“Humanin has demonstrated protective capacity in age-related diseases such as T2DM and Alzheimer’s disease (Mahboobi et al., 2014) and is able to restore mitochondrial function after oxidative injury in retinal pigment epithelial cells (Sreekumar et al., 2016).”
BackgroundMOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism
Lee, C., Kim, K. H., & Cohen, P. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.05.015 · Cited by 178 · cited 1× · see citing works
“The short open reading frame found within the mitochondrial 12S rRNA known as MOTS-C (mitochondrial open reading frame of the 12S rRNA-c) appears mainly in skeletal muscle and activate AMPK (Lee et al., 2016).”
BackgroundMitochondrial genes as sites of primary action of steroid hormones
Demonacos, C. V., Karayanni, N., Hatzoglou, E., Tsiriyiotis, C., Spandidos, D. A., & Sekeris, C. E. (1996) · Steroids · doi:10.1016/0039-128x(96)00019-0 · Cited by 177 · cited 1× · see citing works
“In fact, these elements have been found in mtDNA accompanied by oestrogen and androgen receptors (Demonacos et al., 1995; Demonacos et al., 1996).”
BackgroundMitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1β
Liesa, M., Borda-d'Agua, B., Medina‐Gómez, G., Lelliott, C. J., Paz, J. C., Rojo, M., Palacı́n, M., Vidal‐Puig, A., & Zorzano, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003613 · Cited by 175 · see citing works
Mitochondrial dynamics in the central regulation of metabolism
Nasrallah, C. M., & Horváth, T. L. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.160 · Cited by 167 · cited 1× · see citing works
“It has been suggested that the activity of these neurons is importantly affected by mitochondrial dynamics (Nasrallah and Horvath, 2014).”
BackgroundAlterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes Mellitus
Koliaki, C. C., & Roden, M. (2016) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071715-050656 · Cited by 167 · cited 1× · see citing works
“Interestingly, in these cases a transient increase in oxidative capacity was found in human liver at the same time that oxidative stress increases (Koliaki and Roden, 2016).”
BackgroundWang, C., Wang, C., Huang, H., & Wei, Y. (2013) · The FEBS Journal · doi:10.1111/febs.12096 · Cited by 165 · cited 1× · see citing works
“…mitochondrial dysfunction by blocking respiration or knocking down the mitochondrial transcription factor A induce insulin resistance in human adipocytes and affects the secretion of adiponectin in an effect attributed to the increase in ROS production by defective mitochondria (Wang et al., 2013).”
BackgroundSteinberg, G. R., O'Neill, H. M., Dzamko, N. L., Galic, S., Naim, T., Koopman, R., Jørgensen, S. B., Honeyman, J., Hewitt, K., Chen, Z.-P., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.102434 · Cited by 164 · see citing works
Liu, X., Chan, H. C., Ding, G., Cai, J., Song, Y., Wang, T., Zhang, D., Chen, H., Yu, M. K., Wu, Y., et al. (2015) · Aging Cell · doi:10.1111/acel.12331 · Cited by 164 · see citing works
Merkwirth, C., Martinelli, P., Korwitz, A., Morbin, M., Brönneke, H. S., Jordan, S. D., Rugarli, E. I., & Langer, T. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003021 · Cited by 162 · cited 2× · see citing works
“Moreover, inactivation of PHB-2 in mice brain affects mitochondrial structure and activity resulting in neurodegeneration by hyperphosphorylation of Tau (Merkwirth et al., 2012) or alters beta-cell function in pancreas producing diabetes (Supale et al., 2013).”
BackgroundBody Composition Remodeling and Mortality: The Health Aging and Body Composition Study
Santanasto, A. J., Goodpaster, B. H., Kritchevsky, S. B., Miljkovic, I., Satterfield, S., Schwartz, A. V., Cummings, S. R., Boudreau, R. M., Harris, T. B., & Newman, A. B. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw163 · Cited by 162 · see citing works
Signaling networks determining life span
Riera, C. E., Merkwirth, C., De Magalhaes Filho, C. D., & Dillin, A. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014451 · Cited by 161 · see citing works
Kang, T., Lu, W., Xu, W., Anderson, L. M., Bacanamwo, M., Thompson, W. E., Chen, Y. E., & Liu, D. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.514372 · Cited by 154 · cited 1× · see citing works
“On the other hand, downregulation of PHB by microRNA27a and 27b resulted in impaired mitochondrial biogenesis and structure integrity, lower activity of complex I and higher ROS production in adiposederived stem cells (Kang et al., 2013).”
Backgroundde Brito, O. M., & Scorrano, L. (2009) · Mitochondrion · doi:10.1016/j.mito.2009.02.005 · Cited by 153 · cited 1× · see citing works
“Mfn2 is also associated in the connection between mitochondria and the endoplasmic reticulum (ER) playing a role in the development of endoplasmic reticulum (ER) stress and fat accumulation in conditions of metabolic stress (de Brito and Scorrano, 2008, 2009).”
BackgroundSantel, A., & Frank, S. (2008) · IUBMB Life · doi:10.1002/iub.71 · Cited by 147 · cited 1× · see citing works
“DRP1 is recruited on the outer mitochondrial membrane by FIS1 which is already inserted in this membrane (Santel and Frank, 2008; Yoon et al., 2003).”
BackgroundRhee, S. G., & Bae, S. H. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.007 · Cited by 141 · cited 3× · see citing works
“Nrf2 activation by inhibition of mTORC1 (Rhee and Bae, 2015) probably by”
BackgroundHolmström, M. H., Iglesias-Gutierrez, E., Zierath, J. R., & Garcia-Roves, P. M. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00159.2011 · Cited by 137 · cited 2× · see citing works
“, 2012) and with insulin resistance in the same mice model (Holmstrom et al., 2012).”
BackgroundGouspillou, G., Sgarioto, N., Norris, B. A., Barbat‐Artigas, S., Aubertin‐Leheudre, M., Morais, J. A., Burelle, Y., Taivassalo, T., & Hepple, R. T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103044 · Cited by 133 · cited 1× · see citing works
“…mass and the adaptation to energy demand since this transcriptional coactivator stimulates mitochondrial biogenesis, regulates mitochondrial dynamics, modulates oxidative phosphorylation and controls mitochondrial genome copy number (Gouspillou et al., 2014; Handschin and Spiegelman, 2006).”
BackgroundDolinsky, V. W., Rogan, K. J., Sung, M. M., Zordoky, B. N., Haykowsky, M. J., Young, M. E., Jones, L. W., & Dyck, J. R. B. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00044.2013 · Cited by 133 · cited 2× · see citing works
“…conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are 21 associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans (Cartoni et al., 2005; Dolinsky et al., 2013; Soriano et al., 2006).”
BackgroundDemonacos, C., Djordjevic-Markovic, R., Tsawdaroglou, N., & Sekeris, C. E. (1995) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(95)00159-w · Cited by 131 · see citing works
The Interplay Between Respiratory Supercomplexes and ROS in Aging
Genova, M. L., & Lenaz, G. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6214 · Cited by 126 · cited 2× · see citing works
“Thus, a progressive deterioration of supercomplexes in during ageing could be 12 the cause of an irreversible increase in ROS during ageingin older organisms (Genova and Lenaz, 2015).”
BackgroundMitochondria: Participation to infertility as source of energy and cause of senescence
Benkhalifa, M., Ferreira, Y. J., Chahine, H., Louanjli, N., Miron, P., Merviel, P., & Copin, H. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.08.011 · Cited by 120 · cited 2× · see citing works
“, 2015; Payne and Chinnery, 2015), most data suggest that there is an increase in oxidative damage in the elderly affecting senescence (Lu and Finkel, 2008), fertility declining (Benkhalifa et al., 2014), skin ageing (Kammeyer and Luiten, 2015), neutrophils’ activity (Kovalenko et al.”
BackgroundProhibitin Is a Novel Regulator of Antioxidant Response That Attenuates Colonic Inflammation in Mice
Theiss, A. L., Vijay–Kumar, M., Obertone, T. S., Jones, D. P., Hansen, J. M., Gewirtz, A. T., Merlin, D., & Sitaraman, S. V. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.03.033 · Cited by 113 · see citing works
Biel, T. G., Lee, S., Flores‐Toro, J., Dean, J. W., Go, K. L., Lee, M.-H., Law, B. K., Law, M. E., Dunn, W. A., Zendejas, I. R., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.96 · Cited by 110 · cited 1× · see citing works
“The short open reading frame found within the mitochondrial 12S rRNA known as MOTS-C (mitochondrial open reading frame of the 12S rRNA-c) appears mainly in skeletal muscle and activate AMPK (Lee et al., 2016).”
BackgroundImpaired quality control of mitochondria: Aging from a new perspective
Weber, T. A., & Reichert, A. S. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.018 · Cited by 110 · cited 4× · see citing works
“Moreover, in a model of longevity in Drosophila it has been recently demonstrated that moderated levels of ROS can induce prolongevity effects (Scialo et al., 2016) by activating recycling mechanisms such as mitophagy and autophagy (Weber and Reichert, 2010).”
BackgroundInfluentialMitochondrial Metabolic Reprogramming Induced by Calorie Restriction
Martín‐Montalvo, A., & de Cabo, R. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4866 · Cited by 109 · see citing works
The mitochondrial‐derived peptide <scp>MOTS</scp> ‐c: a player in exceptional longevity?
Fuku, N., Pareja‐Galeano, H., Zempo, H., Alis, R., Arai, Y., Lucia, A., & Hirose, N. (2015) · Aging Cell · doi:10.1111/acel.12389 · Cited by 98 · see citing works
Tao, R., Xiong, X., Liangpunsakul, S., & Dong, X. C. (2015) · Diabetes · doi:10.2337/db14-0539 · Cited by 96 · cited 1× · see citing works
“On the other hand, Sens3 has been recently associated with the activation of mTORC2 and Akt phosphorylation enhancing insulin sensitivity and glucose metabolism in mice (Tao et al., 2015).”
BackgroundSupale, S., Thorel, F., Merkwirth, C., Gjinovci, A., Herrera, P. L., Scorrano, L., Meda, P., Langer, T., & Maechler, P. (2013) · Diabetes · doi:10.2337/db13-0152 · Cited by 94 · cited 2× · see citing works
“Moreover, inactivation of PHB-2 in mice brain affects mitochondrial structure and activity resulting in neurodegeneration by hyperphosphorylation of Tau (Merkwirth et al., 2012) or alters beta-cell function in pancreas producing diabetes (Supale et al., 2013).”
BackgroundMitochondrial elongation during autophagy
Gomes, L. C., & Scorrano, L. (2011) · Autophagy · doi:10.4161/auto.7.10.16771 · Cited by 93 · cited 2× · see citing works
“Thus, the decrease of fission process would allow mitochondria to escape autophagic degradation and then, to maintainmaintaining enough ATP production even with deficient mitochondria (Gomes and Scorrano, 2011).”
BackgroundThe fat cell senescence hypothesis
Newsholme, P., & de Bittencourt, P. I. H. (2014) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000077 · Cited by 90 · cited 3× · see citing works
“8 induced by CR in mice and human muscle (Civitarese et al., 2007; Nisoli et al., 2005) being essential in the CR-induced mitochondrial biogenesis since in eNOS-/- mice this induction is blocked (Nisoli et al.”
BackgroundInfluentialHou, Y.-S., Guan, J.-J., Xu, H.-D., Wu, F., Sheng, R., & Qin, Z.-H. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00285-15 · Cited by 87 · cited 1× · see citing works
“The same mechanism has been associated with the protective effect of sestrin2 in rodent dopaminergic neurons against rotenone toxicity (Hou et al., 2015).”
BackgroundGram, M., Vigelsø, A., Yokota, T., Helge, J. W., Dela, F., & Hey‐Mogensen, M. (2015) · The Journal of Physiology · doi:10.1113/jp270211 · Cited by 86 · cited 2× · see citing works
“Although the role of mitochondria as the major source of intracellular ROS production in ageing has been questioned during the last years (Gram et al., 2015; Payne and Chinnery, 2015), most data suggest that there is an increase in oxidative damage in the elderly affecting senescence (Lu and…”
BackgroundJin, S. H., Yang, J. H., Shin, B. Y., Seo, K., Shin, S. M., Cho, I. J., & Ki, S. H. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.04.023 · Cited by 83 · cited 2× · see citing works
“Resveratrol (RSV), a polyphenol that prevents lipid accumulation in liver, blocks Liver X receptor (LXRα)-mediated hepatic lipogenesis by inducing Sens2 gene (Jin et al., 2013), indicating a putative role of this family of proteins in fat accumulation.”
BackgroundPeng, J., Ren, K., Yang, J., & Luo, X. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.03.007 · Cited by 83 · see citing works
Toledo, F. G. S., & Goodpaster, B. H. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.06.018 · Cited by 82 · cited 2× · see citing works
“In humans, it has been shown that insulin resistance is responsible of the increase of lipids in liver and skeletal muscle and the decrease of the capacity of adipose tissue to store lipids (Toledo and Goodpaster, 2013).”
BackgroundMitochondrial dynamics: orchestrating the journey to advanced age
Biala, A. K., Dhingra, R., & Kirshenbaum, L. A. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.04.015 · Cited by 82 · cited 4× · see citing works
“…defects in mitochondrial fusion/fission dynamics are also essential for the quality control of mitochondria in many age-related diseases as in the case of cardiac homeostasis and senescence (Biala et al., 2015), or in neurodegeneration and hypothalamic dysfunction (Zorzano and Claret, 2015).”
BackgroundInfluentialImplications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction
Zorzano, A., & Claret, M. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00101 · Cited by 79 · cited 2× · see citing works
“…defects in mitochondrial fusion/fission dynamics are also essential for the quality control of mitochondria in many age-related diseases as in the case of cardiac homeostasis and senescence (Biala et al., 2015), or in neurodegeneration and hypothalamic dysfunction (Zorzano and Claret, 2015).”
BackgroundCavalcanti‐de‐Albuquerque, J. P., Salvador, I. C., Martins, E. L., Messeder, D. J., Werneck‐de‐Castro, J. P., Galina, A., & de Carvalho, D. P. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00121.2013 · Cited by 79 · see citing works
Obesity and diabetes: the link between adipose tissue dysfunction and glucose homeostasis
Abranches, M. V., de Oliveira, F. C. E., da Conceição, L. L., & Pelúzio, M. D. C. G. (2015) · Nutrition Research Reviews · doi:10.1017/s0954422415000098 · Cited by 78 · see citing works
Effects of testosterone on body composition of the aging male
Mudali, S. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.01.004 · Cited by 77 · cited 1× · see citing works
“In men, the decrease in testosterone levels can be responsible of the increase of adiposity and fat accumulation in non-adipose tissue during ageing (Mudali and Dobs, 2004).”
BackgroundDietary restriction: standing up for sirtuins
Baur, J. A., Chen, D., Chini, E. N., Chua, K., Cohen, H. Y., Cabo, R. D., Deng, C., Dimmeler, S., Gius, D., Guarente, L. P., et al. (2010) · Science · doi:10.1126/science.329.5995.1012 · Cited by 76 · see citing works
Borengasser, S. J., Faske, J., Kang, P., Blackburn, M. L., Badger, T. M., & Shankar, K. (2014) · Physiological Genomics · doi:10.1152/physiolgenomics.00059.2014 · Cited by 76 · see citing works
Fabbri, E., Chia, C. W., Spencer, R. G., Fishbein, K. W., Reiter, D. A., Cameron, D., Zane, A. C., Moore, Z. A., Gonzalez-Freire, M., Zoli, M., et al. (2017) · Diabetes · doi:10.2337/db16-0754 · Cited by 76 · see citing works
Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells
Scheller, K., Seibel, P., & Sekerist, C. E. (2003) · International review of cytology · doi:10.1016/s0074-7696(02)22011-2 · Cited by 73 · cited 1× · see citing works
“In agreement with this, oestrogens and androgens can affect the transcription of mitochondria OXPHOS components (Scheller et al., 2003).”
BackgroundSESN-1 is a positive regulator of lifespan in Caenorhabditis elegans
Yang, Y.-L., Loh, K.-S., Liou, B.-Y., Chu, I., Kuo, C., Chen, H., & Chen, C. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2012.12.011 · Cited by 72 · see citing works
Anti-Inflammatory Effect of Resveratrol in Old Mice Liver
Tung, B. T., Rodríguez-Bies, E., Talero, E., Gamero-Estévez, E., Motilva, V., Navas, P., & López-Lluch, G. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.02.004 · Cited by 71 · cited 3× · see citing works
“…that NLRP3 activity increases in mouse liver during ageing but this activity is inhibited by RSV probably by reducing the level of oxidative stress increasing the mitochondrial turnover and eliminating by this mechanism ROS-producing deficient mitochondria (Baur et al., 2006; Tung et al., 2015a).”
BackgroundSelf-citationAnde, S. R., Nguyen, K. H., Padilla-Meier, G. P., Wahida, W., Nyomba, B. L. G., & Mishra, S. (2014) · Diabetes · doi:10.2337/db13-1807 · Cited by 71 · see citing works
Nakatsu, Y., Sakoda, H., Kushiyama, A., Zhang, J., Ono, H., Fujishiro, M., Kikuchi, T., Fukushima, T., Yoneda, M., Ohno, H., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.206904 · Cited by 69 · cited 1× · see citing works
“Regarding this aspect, a new regulator of AMPK, prolyl isomerase, Pin1, has been shown to rise in high fat state in mouse liver (Nakatsu et al., 2011).”
BackgroundRapamycin-induced metabolic defects are reversible in both lean and obese mice
Liu, Y., Diaz, V., Fernandez, E., Strong, R., Ye, L., Baur, J. A., Lamming, D. W., Richardson, A., & Salmon, A. B. (2014) · Aging · doi:10.18632/aging.100688 · Cited by 68 · cited 2× · see citing works
“Although rapamycin has been associated with 21 the prevention of age-related diseases and the extension of lifespan in both, obese and lean mice (Liu et al., 2014) and to avoid hyperlipidemia and diabetes-like syndrome in aged obese rats (Scarpace et al., 2016), a recent paper indicate that…”
BackgroundRapamycin Increases Mortality in<i>db/db</i>Mice, a Mouse Model of Type 2 Diabetes
Sataranatarajan, K., Ikeno, Y., Bokov, A., Feliers, D., Yalamanchili, H., Lee, H. J., Mariappan, M. M., Tabatabai-Mir, H., Diaz, V., Prasad, S., et al. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glv170 · Cited by 65 · see citing works
The influence of age and aerobic fitness: effects on mitochondrial respiration in skeletal muscle
Larsen, S., Hey‐Mogensen, M., Rabøl, R., Stride, N., Helge, J. W., & Dela, F. (2012) · Acta Physiologica · doi:10.1111/j.1748-1716.2012.02408.x · Cited by 63 · cited 1× · see citing works
“In human muscle, ageing is accompanied by a higher need of mitochondria to maintain the same respiratory capacity as in young people indicating decay in mitochondrial efficiency (Larsen et al., 2012).”
BackgroundThe mitochondrial genome: a possible primary site of action of steroid hormones.
Sekeris, C. E. (1992) · PubMed · Cited by 62 · see citing works
Tung, B. T., Rodríguez-Bies, E., Ballesteros-Simarro, M., Motilva, V., Navas, P., & López-Lluch, G. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt102 · Cited by 60 · see citing works
Benigni, A., Perico, L., & Macconi, D. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6682 · Cited by 58 · cited 1× · see citing works
“For further information, this mechanism and others have been recently reviewed in deep in its role in ageing and ageing-related diseases (Benigni et al., 2016).”
BackgroundSIRT1 limits adipocyte hyperplasia through c-Myc inhibition
Abdesselem, H., Madani, A., Hani, A., Al-Noubi, M., Goswami, N., Ben Hamidane, H., Billing, A. M., Pasquier, J., Bonkowski, M. S., Halabi, N., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.675645 · Cited by 56 · cited 3× · see citing works
“This indicates that SIRT1 is needed for a correct regulation of the adipose tissue function (Abdesselem et al., 2016).”
BackgroundInfluentialOrgan and tissue-dependent effect of resveratrol and exercise on antioxidant defenses of old mice
Tùng, B. T., Rodríguez-Bies, E., Thanh, H. N., Le‐Thi‐Thu, H., Navas, P., Sánchez, V. M., & López‐Lluch, G. (2015) · Aging Clinical and Experimental Research · doi:10.1007/s40520-015-0366-8 · Cited by 55 · cited 3× · see citing works
“…that NLRP3 activity increases in mouse liver during ageing but this activity is inhibited by RSV probably by reducing the level of oxidative stress increasing the mitochondrial turnover and eliminating by this mechanism ROS-producing deficient mitochondria (Baur et al., 2006; Tung et al., 2015a).”
BackgroundSelf-citationActions of 17β-estradiol and testosterone in the mitochondria and their implications in aging
Vasconsuelo, A., Milanesi, L., & Boland, R. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.09.001 · Cited by 55 · cited 3× · see citing works
“These oestrogens would directly regulate nuclear DNA-encoded proteins and mitochondrial transcription factors affecting by this mechanism mitochondrial biogenesis (Vasconsuelo et al., 2013).”
BackgroundInsulin resistance and mitochondrial function in skeletal muscle
Dela, F., & Helge, J. W. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.09.019 · Cited by 53 · cited 3× · see citing works
“30 performed in rats suggested that insulin resistance is accompanied by an increase in mitochondrial content and an increase in oxidation of lipids (Dela and Helge, 2013; Garcia-Roves et al., 2007; Hancock et al., 2008; Turner et al., 2007).”
BackgroundJin, J., Gu, H., Anders, N. M., Ren, T., Jiang, M., Tao, M., Peng, Q., Rudek, M. A., & Duan, W. (2016) · NeuroMolecular Medicine · doi:10.1007/s12017-016-8412-z · Cited by 50 · cited 2× · see citing works
“protection of mitochondria in huntington’s disease by affecting mitochondrial dynamics (Jin et al., 2016).”
BackgroundThe human mitochondrial genome may code for more than 13 proteins
Capt, C., Passamonti, M., & Breton, S. (2015) · Mitochondrial DNA Part A · doi:10.3109/19401736.2014.1003924 · Cited by 48 · cited 2× · see citing works
“Other 19 mitochondrial-derived peptide is humanin, a 24 aminoacid peptifde encoded within the 16S ribosomal RNA gene (Capt et al., 2016), this peptide has been proposed to produce strong cytoprotective actions against various stress and diseases (Lee et al., 2013a).”
BackgroundThe role of inflammasome modulation in virulence
Lupfer, C. R., & Kanneganti, T. (2012) · Virulence · doi:10.4161/viru.20266 · Cited by 43 · cited 2× · see citing works
“After recognizing PAMPs or DAMPs, Casp-1 is activated and catalyses the transformation of proinflammatory cytokines to their mature forms (Lupfer and Kanneganti, 2012).”
BackgroundNakatsu, Y., Iwashita, M., Sakoda, H., Ono, H., Nagata, K., Matsunaga, Y., Fukushima, T., Fujishiro, M., Kushiyama, A., Kamata, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.658559 · Cited by 43 · cited 1× · see citing works
“This increase is associated with the accumulation of fat since in Pin1 KO mice, a high fat diet-induced obesity resistant phenotype has been described (Nakatsu et al., 2015).”
BackgroundChung, K. W., Lee, E. K., Kim, D. H., An, H. J., Kim, N. D., Im, D. S., Lee, J., Yu, B. P., & Chung, H. Y. (2015) · Aging Cell · doi:10.1111/acel.12305 · Cited by 41 · cited 2× · see citing works
“Moreover, chronically overactive inflammasome activity and production of IL-1β has been associated with the abnormal lipid accumulation in old rat liver resulting in steatohepatitis (Chung et al., 2015).”
BackgroundMuscle wasting: an overview of recent developments in basic research
Palus, S., von Haehling, S., & Springer, J. (2014) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-014-0157-7 · Cited by 41 · cited 1× · see citing works
“Furthermore, the activity of this ubiquitin ligase has been recently associated with the maintenance of muscle mass (Palus et al., 2014).”
BackgroundMetformin Treatment Prevents Sedentariness Related Damages in Mice
Senesi, P., Montesano, A., Luzi, L., Codella, R., Benedini, S., & Terruzzi, I. M. (2015) · Journal of Diabetes Research · doi:10.1155/2016/8274689 · Cited by 40 · cited 1× · see citing works
“In the case of metformin, it has been associated with the prevention of sedentarism-dependent damages (Senesi et al., 2016).”
BackgroundSastre-Serra, J., Nadal-Serrano, M., Pons, D. G., Roca, P., & Oliver, J. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.07.012 · Cited by 40 · cited 1× · see citing works
“The same effect was found in other breast cancer cell lines (Sastre-Serra et al., 2013).”
BackgroundResveratrol primes the effects of physical activity in old mice
Rodríguez-Bies, E., Tung, B. T., Navas, P., & López-Lluch, G. (2016) · British Journal Of Nutrition · doi:10.1017/s0007114516002920 · Cited by 40 · cited 1× · see citing works
“If ROS production is balanced with antioxidant enzymes, oxidative damage did not occur, but if these enzymes decay during aging, as has been found in different models (Rodriguez-Bies et al., 2015; Rodriguez-Bies et al., 2016; Tung et al., 2014; Tung et al., 2015b), oxidative damage accumulates.”
BackgroundSelf-citationOx-Lp(a) transiently induces HUVEC autophagy via an ROS-dependent PAPR-1-LKB1–AMPK–mTOR pathway
Li, G.-H., Lin, X., Zhang, H., Li, S., He, X., Zhang, K., Peng, J., Tang, Y., Zeng, J., Zhao, Y., et al. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.09.020 · Cited by 38 · cited 2× · see citing works
“Although the ROS-dependent mechanisms involved in the increase of mitochondrial metabolism have to be clarified, it seems that the AMPK-dependent modulation of FoxO-dependent autophagy and PGC1α-regulated mitochondrial biogenesis are involved (Li et al., 2015).”
BackgroundKovalenko, E. I., Boyko, A. A., Semenkov, V. F., Lutsenko, G. V., Grechikhina, M. V., Kanevskiy, L. M., Azhikina, T. L., Telford, W. G., & Sapozhnikov, A. M. (2014) · Oncotarget · doi:10.18632/oncotarget.2856 · Cited by 38 · see citing works
Nutrient sensing and utilization: getting to the heart of metabolic flexibility
Griffin, T. M., Humphries, K. M., Kinter, M., Lim, H.-Y., & Szweda, L. I. (2016) · Biochimie · doi:10.1016/j.biochi.2015.10.013 · Cited by 36 · cited 4× · see citing works
“This impairment is known as “metabolic inflexibility” (Griffin et al., 2015), that is present in obese people since they are able to oxidize lipids in insulin-stimulated conditions instead to metabolize glucose being mitochondria the key organelles affecting this incapacity (Storlien et al., 2004).”
BackgroundInfluentialEstrogen-Regulated Prohibitin Is Required for Mouse Uterine Development and Adult Function
He, B., Kim, T. H., Kommagani, R., Feng, Q. F., Lanz, R. B., Jeong, J., DeMayo, F. J., Katzenellenbogen, B. S., Lydon, J. P., & O’Malley, B. W. (2011) · Endocrinology · doi:10.1210/en.2010-0732 · Cited by 36 · cited 1× · see citing works
“Studies performed in other tissues demonstrated that prohibitin genes are induced by oestrogen receptors (He et al., 2011).”
BackgroundRodríguez-Bies, E., Navas, P., & López-Lluch, G. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu002 · Cited by 36 · cited 3× · see citing works
“interventions such as CR, exercise or nutraceuticals as resveratrol also induce mitochondrial biogenesis in humans and other organisms (Baur et al., 2010; Feige et al., 2008; Rodriguez-Bies et al., 2015).”
BackgroundSelf-citationSestrins: Novel antioxidant and AMPK‐modulating functions regulated by exercise?
Sanchis‐Gomar, F. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24338 · Cited by 36 · cited 2× · see citing works
“In fact, although no studies have been performed yet in humans, the activity of sestrins has been recently suggested in the effect of exercise to prevent sarcopenia, frailty and obesity in the elderly (Sanchis-Gomar, 2013).”
BackgroundJheng, H.-F., Huang, S.-H., Kuo, H.-M., Hughes, M. W., & Tsai, Y. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12863 · Cited by 34 · cited 1× · see citing works
“In fact, the elucidation of the mechanisms affecting mitochondrial dynamics in skeletal muscle from obese people has been suggested to be essential to understand muscle insulin resistance and to find therapeutic targets (Jheng et al., 2015).”
BackgroundSastre-Serra, J., Nadal-Serrano, M., Pons, D. G., Roca, P., & Oliver, J. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.04.007 · Cited by 34 · cited 1× · see citing works
“The same effect was found in other breast cancer cell lines (Sastre-Serra et al., 2013).”
BackgroundMitohormesis in muscle cells: a morphological, molecular, and proteomic approach
Berberi, E., Sestili, P., Vallorani, L., Guescini, M., Calcabrini, C., Gioacchini, A. M., Annibalini, G., Lucertini, F., Piccoli, G., & Stocchi, V. (2019) · Muscles Ligaments and Tendons Journal · doi:10.32098/mltj.04.2013.05 · Cited by 31 · cited 5× · see citing works
“…accumulation of damaged mitochondria would explain the increase of ROS in skeletal muscle associated with insulin resistance of obese individuals and the appearance of T2DM and muscle malfunction during normal ageing as results of the deteriorated physiology of the organs (Barbieri et al., 2013).”
BackgroundInfluentialRapamycin Normalizes Serum Leptin by Alleviating Obesity and Reducing Leptin Synthesis in Aged Rats
Scarpace, P. J., Matheny, M. E., Strehler, K. Y. E., Toklu, H. Z., Kirichenko, N., Carter, C. S., Morgan, D., & Tümer, N. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu230 · Cited by 31 · see citing works
Transcriptional Role of FOXO1 in Drug Resistance through Antioxidant Defense Systems
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“FoxO are involved in the induction of several stress response genes (Goto and Takano, 2009) highlighting their importance in the induction of protective mechanisms in the organisms.”
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“Prohibitin is a complex of two proteins, PHB-1 and PHB-2, that has been associated with longevity in studies carried out in worms (Lourenco et al., 2015).”
BackgroundThe mitochondrion as a primary site of action of regulatory agents involved in neuroimmunomodulation
PSARRA, A. M. G., SOLAKIDI, S., & SEKERIS, C. E. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1366.019 · Cited by 22 · cited 4× · see citing works
“The appropriate receptors can interact with these sequences to induce hormone-dependent mitochondrial gene expression (Psarra et al., 2006).”
BackgroundInfluentialHumanin: a possible linkage between Alzheimer's disease and type 2 diabetes
Mahboobi, H., Golmirzaei, J., Gan, S., Jalalian, M., & Kamal, M. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527312666131223110147 · Cited by 21 · cited 1× · see citing works
“Humanin has demonstrated protective capacity in age-related diseases such as T2DM and Alzheimer’s disease (Mahboobi et al., 2014) and is able to restore mitochondrial function after oxidative injury in retinal pigment epithelial cells (Sreekumar et al., 2016).”
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“Mitochondrial dysregulation is also thought to contribute to physiological processes associated with aging [64,65].”
BackgroundZhang, Y., Wang, Y., Xu, J., Tian, F., Hu, S., Chen, Y., & Fu, Z. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12542 · Cited by 393 · see citing works
Estrogenic control of mitochondrial function
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“activation of their respective receptors [108].”
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“Mitochondria are major organelles for energy and intermediate metabolite production, with critical roles in the aging process (Lopez-Lluch, 2017).”
BackgroundForkhead Box O Signaling Pathway in Skeletal Muscle Atrophy
Chen, K., Gao, P., Li, Z., Dai, A., Yang, M. W. O., Chen, S., Su, J., Deng, Z., & Li, L. (2022) · American Journal Of Pathology · doi:10.1016/j.ajpath.2022.09.003 · Cited by 122 · see citing works
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“…several other factors may influence the magnitude of change in mitochondrial content in response to exercise training (i.e., the “trainability”), including initial fitness level, age, sex, menopause, degree of active muscle mass engaged during exercise, and the presence of disease [17–21].”
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Age-related mitochondrial dysfunction as a key factor in COVID-19 disease
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“Mitochondrial dysfunction is deeply associated with two of these factors, aging and obesity (Lopez-Lluch, 2017b).”
InfluentialSelf-citationRole of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease
Li, R., Toan, S., & Zhou, H. (2020) · Aging · doi:10.18632/aging.102972 · Cited by 90 · see citing works
“Furthermore, MiD49 and MiD51 can recruit Drp1 to the mitochondria in the absence of Mff and Fis1 [101, 102].”
BackgroundInfluentialMechanisms behind therapeutic potentials of mesenchymal stem cell mitochondria transfer/delivery
Malekpour, K., Hazrati, A., Soudi, S., & Hashemi, S. M. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.01.059 · Cited by 84 · see citing works
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“Mitochondrial fusion and fission require the regulation of key proteins, including the mitochondrial fusion proteins such as Opa1, Mfn1, and Mfn2 and the mitochondrial fission proteins such as Drp1 and Fis1, which are regulated by PGC-1α (Lopez-Lluch, 2017).”
BackgroundThe importance of estradiol for body weight regulation in women
Pilar Vigil, P., Meléndez, J., Petkovic, G., & Río, J. P. D. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.951186 · Cited by 82 · see citing works
Exercise and mitochondrial mechanisms in patients with sarcopenia
Pahlavani, H. A., Laher, I., Knechtle, B., & Zouhal, H. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1040381 · Cited by 76 · see citing works
“Hence, decreased PHB impairs mitochondrial biogenesis and structural integrity, leading to a decrease in complex I efficiency and an increase in ROS formation (López-Lluch, 2017).”
BackgroundModeration of mitochondrial respiration mitigates metabolic syndrome of aging
Tavallaie, M. S., Voshtani, R., Deng, X., Qiao, Y., Jiang, F., Collman, J. P., & Fu, L. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1917948117 · Cited by 69 · see citing works
“The CcO activity of the 14-mo-old untreated control group was ≃ 47% lower than that of the 2-mo-old untreated control, consistent with the concept that mitochondria deteriorate through aging (16).”
BackgroundObesity accelerates cardiovascular ageing
Ruperez, C., Madeo, F., de Cabo, R., Kroemer, G., & Abdellatif, M. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf216 · Cited by 73 · see citing works
“116 Mitochondrial fragmentation, which is evident both in mice and humans, 117,118 is mediated by the small GTPase RalA.”
Drug-Induced Mitochondrial Toxicity in the Geriatric Population: Challenges and Future Directions
Will, Y., Shields, J. E., & Wallace, K. B. (2019) · Biology · doi:10.3390/biology8020032 · Cited by 65 · see citing works
“Molecular hallmarks associated with mitochondrial aging include a decreased mtDNA copy number [29] accompanied by the accumulation of mutations to the mitochondrial genome [30,31], reduced abundance of both nuclear and mitochondrial encoded mRNA [22,32], decreased mitochondrial protein synthesis [33–36], and the dysre…”
BackgroundInfluentialWhy weight loss maintenance is difficult
Evert, A. B., & Franz, M. J. (2017) · Diabetes Spectrum · doi:10.2337/ds017-0025 · Cited by 63 · see citing works
“Although both the environment (4) and mitochondrial dysfunction (5) also contribute to obesity, their roles in weight loss maintenance are less well documented and so are not addressed in this article.”
BackgroundCárdenas-Pérez, R. E., Fuentes‐Mera, L., de la Garza, A. L., Torre-Villalvazo, I., Reyes‐Castro, L. A., Rodríguez‐Rocha, H., García‐García, A., Corona, J. C., Tovar, A. R., Zambrano, E., et al. (2018) · Nutrition & Metabolism · doi:10.1186/s12986-018-0279-6 · Cited by 58 · see citing works
“DRP1 ablation leads to higher ROS production and dysfunctional mitochondria [57].”
BackgroundMitochondrial dysfunction in metabolism and ageing: shared mechanisms and outcomes?
López‐Lluch, G., Hernández‐Camacho, J. D., Fernández‐Ayala, D. J. M., & Navas, P. (2018) · Biogerontology · doi:10.1007/s10522-018-9768-2 · Cited by 57 · see citing works
“Thus, mitochondrial activity, biogenesis, turnover and dynamics respond to main metabolism sensors in cells such as mTOR, AMPK and sirtuins [for a more comprehensive, see (Lopez-Lluch 2017; Lopez-Lluch et al. 2015)].”
BackgroundInfluentialSelf-citationLivshits, G., & Kalinkovich, A. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101852 · Cited by 55 · see citing works
Liu, S., Yu, C., Xie, L., Niu, Y., & Fu, L. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab029 · Cited by 51 · see citing works
Circadian gene Clock regulates mitochondrial morphology and functions by posttranscriptional wayPreprint
Xu, L., Cheng, Q., Hua, B., Cai, T., Lin, J., Yuan, G., Yan, Z., Li, X., Sun, N., Lü, C., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/365452 · Cited by 48 · see citing works
“94 In vivo and vitro experiments have both illustrated that altered mitochondrial 95 dynamics give rise to metabolic block and abnormal quantity of ROS, resulting in 96 metabolic diseases(Liesa & Shirihai, 2013; Lopez-Lluch, 2017; Yoon et al, 2006).”
BackgroundMitochondria as the Essence of Yang Qi in the Human Body
Luo, J., Shiwei, S., Xia, J., Wang, J., & Gu, Z. (2022) · Phenomics · doi:10.1007/s43657-022-00060-3 · Cited by 50 · see citing works
“Scientists have shown that mitochondrial dysfunction is closely related to age-dependent fat accumulation (Lopez-Lluch 2017).”
BackgroundCLOCK regulates Drp1 mRNA stability and mitochondrial homeostasis by interacting with PUF60
Xu, L., Lin, J., Liu, Y., Hua, B., Cheng, Q., Lin, C., Yan, Z., Wang, Y.-P., Sun, N., Qian, R., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110635 · Cited by 42 · see citing works
Modulating mitochondrial dynamics attenuates cardiac ischemia-reperfusion injury in prediabetic rats
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Alternative respiratory chain enzymes: Therapeutic potential and possible pitfalls
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Are Older People Really More Susceptible to SARS-CoV-2?
Zhang, S., Yang, Z., Li, Z.-N., Chen, Z.-L., Yue, S.-J., Fu, R.-J., Xu, D.-Q., Zhang, S., & Tang, Y.-P. (2022) · Aging and disease · doi:10.14336/ad.2022.0130 · Cited by 39 · see citing works
“Mitochondrial dysfunction is closely related to aging and is the main progression of aging and age-related diseases, which plays a very important role in a variety of comorbid diseases [48].”
BackgroundLi, J., Zhang, R., Han, X., & Piao, C. (2018) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20177139 · Cited by 39 · see citing works
“AMPK activation induces cellular catabolism of lipids, protein and sugars via multiple downstream pathways (28).”
BackgroundCoenzyme Q at the Hinge of Health and Metabolic Diseases
Hernández‐Camacho, J. D., García‐Corzo, L., Fernández‐Ayala, D. J. M., Navas, P., & López‐Lluch, G. (2021) · Antioxidants · doi:10.3390/antiox10111785 · Cited by 37 · see citing works
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Marín‐Royo, G., Rodrı́guez, C., Pape, A. L., Jurado-López, R., Luaces, M., Antequera-Pérez, A., Martínez‐González, J., Souza‐Neto, F. V., Nieto, M. L., Martínez‐Martínez, E., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900347rr · Cited by 35 · see citing works
“Obesity is also accompanied by changes in levels of different mitochondrial proteins in EAT, Cyclo F, and MFN1, which are involved in essential processes that can affectmitochondrial survival (27, 28), leading to cell death (29).”
BackgroundGundersen, A. E., Kugler, B. A., McDonald, P. M., Veraksa, A. N., Houmard, J. A., & Zou, K. (2019) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2019-0208 · Cited by 34 · see citing works
Host mitochondria: more than an organelle in SARS-CoV-2 infection
Shoraka, S., Samarasinghe, A. E., Ghaemi, A., & Mohebbi, S. R. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1228275 · Cited by 28 · see citing works
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Diabesity and brain disturbances: A metabolic perspective
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“It is regulated by nutrient sensors such as mTOR, AMPK and sirtuins, maintaining an equilibrium of activity according to the requirement of the cells (López-Lluch 2017).”
BackgroundSumbalová, Z., Kucharská, J., Rausová, Z., Palacka, P., Kovalčíková, E., Takácsová, T., Mojto, V., Navas, P., López‐Lluch, G., & Gvozdjáková, A. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1016352 · Cited by 23 · see citing works
“…incidence of post C-19 is in aged subjects and in patients with comorbidities such as diabetes mellitus, obesity, cardiovascular disease, chronic lung disease, cancer (Lopez-Lluch 2017; Fernandez-Ayala et al., 2020; Huang et al., 2020; Li et al., 2020; Zhang and Liu, 2020; Ganji and Reddy 2021).”
BackgroundSelf-citationMountain spa rehabilitation improved health of patients with post-COVID-19 syndrome: pilot study
Gvozdjáková, A., Sumbalová, Z., Kucharská, J., Rausová, Z., Kovalčíková, E., Takácsová, T., Navas, P., López‐Lluch, G., Mojto, V., & Palacka, P. (2022) · Environmental Science and Pollution Research · doi:10.1007/s11356-022-22949-2 · Cited by 21 · see citing works
“In aged people, dysfunctions of immune system and mitochondrial health are key factors in COVID-19 disease (Lopez-Lluch 2017; Fernandez-Ayala et al. 2020; Ganji and Reddy 2021).”
BackgroundSelf-citationThe Role of Mitochondrial Quality Control in Chronic Obstructive Pulmonary Disease
Liu, Y., Hong, J., Jiang, N., Jin, L., Zhong, W., Zhang, C.-Y., Yang, H., Duan, J., & Zhou, Y. (2023) · Laboratory Investigation · doi:10.1016/j.labinv.2023.100307 · Cited by 21 · see citing works
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Trib1 deficiency causes brown adipose respiratory chain depletion and mitochondrial disorder
Zhang, X., Zhang, B., Zhang, C., Sun, G., & Sun, X. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04389-x · Cited by 17 · see citing works
“In addition to the classical phosphatase and tensin homolog-induced kinase 1-Parkin pathway and GTPases that regulate mitotic fusion proteins and in fl uence mitochondrial dynamics [11, 12], oxidative phosphorylation has been suggested to be closely related to mitochondrial fusion.”
BackgroundBioenergetics: the evolutionary basis of progressive kidney disease
Chevalier, R. L. (2023) · Physiological Reviews · doi:10.1152/physrev.00029.2022 · Cited by 17 · see citing works
Salagre, D., Álvarez, E. R., Cendán, C. M., Aouichat, S., & Agil, A. (2023) · Antioxidants · doi:10.3390/antiox12081499 · Cited by 18 · see citing works
The Hepatokine RBP4 Links Metabolic Diseases to Articular Inflammation
Pazos‐Pérez, A., Piñeiro-Ramil, M., Franco‐Trepat, E., Alonso‐Pérez, A., Guillán‐Fresco, M., Crespo-Golmar, A., López‐Fagúndez, M., Conde, J., Bravo, S. B., Mora, A. J., et al. (2024) · Antioxidants · doi:10.3390/antiox13010124 · Cited by 15 · see citing works
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“[138,158] In conclusion, targeting the AMPK signaling pathway may represent a promising therapeutic strategy for DPN.”
Vial, G., Coudy‐Gandilhon, C., Pinel, A., Wauquier, F., Chevenet, C., Béchet, D., Wittrant, Y., Coxam, V., Soubrier, M., Tournadre, A., et al. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2019.158574 · Cited by 14 · see citing works
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Li, Y., Zhang, N., Ma, C., Xu, W., Jin, G., Zheng, Y., Zhang, L., Liu, B., Gao, C., & Liu, S. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04289-0 · Cited by 13 · see citing works
“Cellular senescence and telomere attrition are important processes which are involved in aging [7].”
BackgroundMitochondrial Autophagy in Ischemic Aged Livers
Js, K., Chapman, W. C., & Lin, Y. (2022) · Cells · doi:10.3390/cells11244083 · Cited by 14 · see citing works
Szemik, S., Zieleń-Zynek, I., Szklarek, E., & Kowalska, M. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1437292 · Cited by 13 · see citing works
Prohibitins: A Key Link between Mitochondria and Nervous System Diseases
Jiang, T., Wang, J., Li, C., Cao, G., & Wang, X. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/7494863 · Cited by 12 · see citing works
The potential role of sestrin 2 in liver regeneration
Oliveira, R. P., Machado, I. F., Palmeira, C. M., & Rolo, A. P. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.12.027 · Cited by 10 · see citing works
Traa, A., González, A. A. T., & Raamsdonk, J. M. V. (2024) · GeroScience · doi:10.1007/s11357-024-01276-z · Cited by 8 · see citing works
Gvozdjáková, A., Kucharská, J., Rausová, Z., López‐Lluch, G., Navas, P., Palacka, P., Bartolčičová, B., & Sumbalová, Z. (2023) · Viruses · doi:10.3390/v15051085 · Cited by 9 · see citing works
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“However, in an obese context, it is admitted that this equilibrium gets disrupted and is linked to mitochondrial dysfunction mechanisms in adipocytes [71].”
BackgroundVerdejo, H., Parra, V., del Campo, A., Vásquez-Trincado, C., Gatica, D., López‐Crisosto, C., Kuzmicic, J., Venegas-Zamora, L., Zúñiga-Cuevas, Ú., Troncoso, M. F., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02240-w · Cited by 8 · see citing works
“They are involved in stabilizing OPA-1 and cristae structure as well as in the maintenance of the mitochondrial genome [14] and regulation of fat metabolism [15, 16].”
Jiang, H., Yang, H., Liu, Y., et al. (2024) · Journal of Cellular Physiology · doi:10.1002/jcp.31169 · Cited by 8 · see citing works
Gender Characteristics of the Novel Coronavirus Infection (COVID-19) in Middle-Aged Adults
Некаева, Е. С., Bol’shakova, A. E., Malysheva, E. S., et al. (2021) · Современные технологии в медицине · doi:10.17691/stm2021.13.4.02 · Cited by 8 · see citing works
“The accumulation of abnormal mitochondria may result from metabolic disorders in diabetes mellitus, oncological, neurodegenerative, and other diseases [14].”
BackgroundGao, Z., Yan, L., & Li, W. (2019) · Antiviral Research · doi:10.1016/j.antiviral.2019.06.002 · Cited by 8 · see citing works
β‐Hydroxybutyrate Acts as an Exercise Mimetic to Protect the Aging Liver
Li, K., Wang, L. Y., Zhu, D., Wang, W., Guo, Y., Gao, H., Zhou, M., & Xiao, W. (2025) · Aging Cell · doi:10.1111/acel.70314 · Cited by 9 · see citing works
“…mitochondrial dynamics have been shown to facilitate lipid accumulation in multiple tissues (e.g., liver, skeletal muscle, kidney) with age and significantly contribute to metabolic diseases such as obesity, metabolic syndrome, and T2DM (Zhao et al. 2014; López-Lluch 2017; Meyer et al. 2017).”
Chiang, C.-H., Li, S., Lin, Y.-H., Wang, P., Hsu, P., Lin, S., Chiang, T.-C., & Chen, C. (2023) · Biogerontology · doi:10.1007/s10522-023-10023-4 · Cited by 7 · see citing works
“2019; Lopez-Lluch 2017).”
BackgroundInfluentialWinkler, S., Hempel, M., Hsu, M., Gericke, M. T., Kühne, H., Brückner, S., Erler, S., Burkhardt, R., & Christ, B. (2019) · Cells · doi:10.3390/cells8080775 · Cited by 7 · see citing works
“These events are not necessarily related to obesity but rather to aging and create a low-grade inflammatory milieu, which increases the susceptibility to metabolic dysfunction in adipose tissue and liver [18,19].”
BackgroundProtocol for Seahorse analysis of ex vivo mouse brown and white adipose tissues
Wang, F., Huynh, P. M., & An, Y. (2024) · STAR Protocols · doi:10.1016/j.xpro.2024.103042 · Cited by 6 · see citing works
Role of Mitochondria in Adipose Tissues Metabolism and Plasticity
Carrière, A., & Casteilla, L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811752-1.00007-9 · Cited by 7 · see citing works
Why is chronic kidney disease progressive? Evolutionary adaptations and maladaptations
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- Authors
- López-Lluch, G.
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 162
- Pages
- 108-121
- ISSN
- 0047-6374 (ISSN-L)
- OpenAlex
- W2567448622
- Semantic Scholar
- 9c089052e93e43300828699c84578230fb2a88d7
- Cited by
- 103
- References
- 205
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 13 · 2021: 10 · 2020: 12 · 2019: 13 · 2018: 9 · 2017: 4
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial dynamics, mitochondrial homeostasis, aging, obesity, mTOR, AMPK, sirtuins, mitochondrial biogenesis, mitochondrial fusion, mitochondrial fission, mitophagy, autophagy, OPA1, Drp1, prohibitin, sestrins, sex hormones, adipose tissue, fat deposition, metabolic syndrome, type 2 diabetes
- MeSH terms
- Aging, Animals, Humans, Membrane Proteins, Microtubule-Associated Proteins, Mitochondria, Obesity, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, Sirtuins, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
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