The DOI matches its Crossref record; 150 of the 151 references it cites were found in a registry or an index; 2 of the 170 sources its claims cite were checked for support.
Mitochondria Initiate and Regulate Sarcopenia
Open accessAbstract
We present the hypothesis that an accumulation of dysfunctional mitochondria initiates a signaling cascade leading to motor neuron and muscle fiber death and culminating in sarcopenia. Interactions between neural and muscle cells that contain dysfunctional mitochondria exacerbate sarcopenia. Preventing sarcopenia will require identifying mitochondrial sources of dysfunction that are reversible.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review proposes that age-related accumulation of dysfunctional mitochondria in muscle cells and motor neurons initiates apoptotic signaling and cell death, leading to sarcopenia, with neural–muscle cross talk exacerbating the process. It argues that preventing sarcopenia requires identifying reversible mitochondrial sources of dysfunction, especially through mitophagy, exercise, and nutrition.
Key findings
- The central hypothesis is that mitochondrial deterioration in muscles and motor neurons is the primary initiator of sarcopenia; increased mPTP opening releases mitochondrial contents to the cytosol, initiating apoptosis and nuclear DNA fragmentation, leading to fiber and motor neuron death.
- Sarcopenia in aged humans and rodents is associated with motor neuronal death, impaired innervation, and a ~27% reduction in the motor unit pool; loss of innervation induces profound muscle atrophy.
- Proposed mitochondrial sources of damage include ROS, mtDNA deletions/mutations, and denervation; aging also attenuates mitophagy, allowing dysfunctional mitochondria to persist, with Mfn2 decline implicated as a possible bridge, though conflicting data exist.
- Exercise and nutritional interventions are proposed to improve mitochondrial health by increasing mitophagy and mitochondrial biogenesis, but the paper notes uncertainty about whether new mitochondria in aged hosts are healthy and whether antioxidants should be used when elderly begin exercise.
Methods
- Design: conceptual/hypothesis review; no primary experimental study is reported.
- Data or sample: Not stated in the paper; the paper cites published studies in aged humans, rodents, and cell/mouse models rather than presenting its own sample.
- Main analysis: narrative synthesis and development of hypothetical models (Figures 1 and 2); no formal statistical or systematic analysis is reported.
Limitations
- The paper states the hypothesis is based on speculation and requires additional work; it specifically notes lack of data for aging-associated localized motor neuron disassembly outside neural degenerative disease.
- The paper acknowledges conflicting evidence, including whether Mfn2 declines or mitophagy is reduced in aged muscle, and inconsistent UPS/atrogene findings across studies.
- Evident from the text: as a narrative review, it provides no primary data, systematic search, or causal test of the mitochondrial-initiation hypothesis.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
80 Not checked yet · 26 Own interpretation · 1 Partly supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“studies that have reported a higher fusion index in muscles from old rodents as indicated by ratios of Mfn1/Mfn2 (63) or Mfn2/Drp1 (75) did not find changes in the protein contents of Mfn1, Mfn2, Opa1 or Drp1.”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death > Altered mitochondrial dynamics with aging
What the sources say
- Partly supportedcites [63] Joseph AM Adhihetty PJ Wawrzyniak NR Wohlgemuth SE Picca A Kujoth GC Prolla TA Leeuwenburgh C Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging PLoS. One 2013 8 e69327 23935986 PMC3720551 sourceExperimental — accuracy not yet measured
The Results (‘Altered Mitochondrial Morphology Proteins in mtDNA Mutator Mice’) report no changes in Opa1 or Drp1, supporting that part of the claim. But Mfn1 and Mfn2 were significantly higher in older than younger mice, so the claim that their protein contents did not change is not supported. Table 1 in the Discussion confirms this distinction for normally aging mice. (LLM, conf=0.88)
- Supportedcites [75] Leduc-Gaudet JP Picard M Jean PF St Sgarioto N Auger MJ Vallee J Robitaille R Pierre DH St Gouspillou G Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice Oncotarget 2015 6 17923 17937 26053100 PMC4627226 source
The Results section (Figure 6) reports a significantly increased Mfn2-to-Drp1 ratio in aged mouse skeletal muscle, while finding no significant differences in Opa1, Mfn1, Mfn2, or Drp1 protein content. This supports the part of the citing sentence attributed to this paper. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
In the paper
“both neural and muscle losses of the cytosolic antioxidant CuZn-superoxide dismutase (CuZnSOD) recapitulated sarcopenic muscle loss in a mouse model (125).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
What the sources say
- Not checked yetcites [125] Sataranatarajan K Qaisar R Davis C Sakellariou GK Vasilaki A Zhang Y Liu Y Bhaskaran S McArdle A Jackson M Brooks SV Richardson A Van RH Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype Redox. Biol 2015 5 140 148 25917273 PMC5022075 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“it is clear that accumulation of excessive ROS contributes to damaged and dysfunctional mitochondria in muscle and neural cells.”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
What the sources say
- Not checked yetcites [15] Brand MD Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling Free Radic. Biol. Med 2016 27085844 source
- Not checked yetcites [125] Sataranatarajan K Qaisar R Davis C Sakellariou GK Vasilaki A Zhang Y Liu Y Bhaskaran S McArdle A Jackson M Brooks SV Richardson A Van RH Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype Redox. Biol 2015 5 140 148 25917273 PMC5022075 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“It is interesting that a loss of mitochondria function with aging is a mechanism that is shared by both muscle cells (18, 63) and motor neurons (123).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction
What the sources say
- Not checked yetcites [18] Calvani R Joseph AM Adhihetty PJ Miccheli A Bossola M Leeuwenburgh C Bernabei R Marzetti E Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy Biol. Chem 2013 394 393 414 23154422 PMC3976204 source
- Not checked yetcites [63] Joseph AM Adhihetty PJ Wawrzyniak NR Wohlgemuth SE Picca A Kujoth GC Prolla TA Leeuwenburgh C Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging PLoS. One 2013 8 e69327 23935986 PMC3720551 source
- Not checked yetcites [123] Rygiel KA Grady JP Turnbull DM Respiratory chain deficiency in aged spinal motor neurons Neurobiol. Aging 2014 35 2230 2238 24684792 PMC4099519 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the absence of CuZnSOD in either neural or muscle cells did not manifest full sarcopenic muscle loss (125).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
What the sources say
- Not checked yetcites [125] Sataranatarajan K Qaisar R Davis C Sakellariou GK Vasilaki A Zhang Y Liu Y Bhaskaran S McArdle A Jackson M Brooks SV Richardson A Van RH Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype Redox. Biol 2015 5 140 148 25917273 PMC5022075 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In aging, a loss of innervation induces profound muscle atrophy (5, 106, 129).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction
What the sources say
- Not checked yetcites [5] Alway SE Degens H Krishnamurthy G Chaudhrai A Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats J Gerontol. A Biol. Sci Med Sci 2003 58 687 697 12902526 source
- Not checked yetcites [106] Pannerec A Springer M Migliavacca E Ireland A Piasecki M Karaz S Jacot G Metairon S Danenberg E Raymond F Descombes P McPhee JS Feige JN A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia Aging (Albany. NY) 2016 8 712 729 27019136 PMC4925824
- Not checked yetcites [129] Siu PM Alway SE Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle J. Physiol 2005 565 309 323 15774533 PMC1464486 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, mitochondrial susceptibility to mPTP opening is a common point which triggers downstream cell destruction in both neuron and muscle cells.”
§ Mitochondria Initiate and Regulate Sarcopenia > Mitochondria permeability transition pore sensitization with aging – mitochondrial dysfunction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“electron microscopy and biochemical analyses have shown small, more fragmented mitochondria in muscles from old as compared to young adult hosts (56, 57)”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death > Altered mitochondrial dynamics with aging
What the sources say
- Not checked yetcites [56] Iqbal S Hood DA The role of mitochondrial fusion and fission in skeletal muscle function and dysfunction Front Biosci. (Landmark. Ed) 2015 20 157 172 25553445 source
- Not checked yetcites [57] Iqbal S Ostojic O Singh K Joseph AM Hood DA Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse Muscle Nerve 2013 48 963 970 23494933 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Defective mitophagy underlies the progression of motor neuron death in Amyotrophic lateral sclerosis (ALS) (38).”
§ Mitochondria Initiate and Regulate Sarcopenia > Insufficient mitophagy allows unhealthy mitochondria to persist in aging muscles and neurons
What the sources say
- Not checked yetcites [38] Fornai F Longone P Ferrucci M Lenzi P Isidoro C Ruggieri S Paparelli A Autophagy and amyotrophic lateral sclerosis: The multiple roles of lithium Autophagy 2008 4 527 530 18367867 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Our model for a localized apoptotic and proteolytic signaling cascade that expands to neighboring regions of a muscle fiber (Figure 2) has strong support from the work of Aiken and co-workers (26, 49, 50).”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death
What the sources say
- Not checked yetcites [26] Cheema N Herbst A McKenzie D Aiken JM Apoptosis and necrosis mediate skeletal muscle fiber loss in age-induced mitochondrial enzymatic abnormalities Aging Cell 2015 14 1085 1093 26365892 PMC4693455 source
- Not checked yetcites [49] Herbst A Pak JW McKenzie D Bua E Bassiouni M Aiken JM Accumulation of mitochondrial DNA deletion mutations in aged muscle fibers: evidence for a causal role in muscle fiber loss J Gerontol. A Biol. Sci. Med. Sci 2007 62 235 245 17389720 PMC2846622 source
- Not checked yetcites [50] Herbst A Wanagat J Cheema N Widjaja K McKenzie D Aiken JM Latent mitochondrial DNA deletion mutations drive muscle fiber loss at old age Aging Cell 2016 PMC5114866 27561813
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 12
- It may state two separate claims as one. 38
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cross talk between muscles and motor neurons that contain dysfunctional mitochondria exacerbates sarcopenia.”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
plaindirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A loss of mitophagy-proteasome-induced mitochondrial clearance in muscle and motor neuron cells promotes accumulation of poorly functioning mitochondria that have increased mPTP opening.”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
plaindirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds.
- Rests on an assumption: Aging suppression of autophagy activators such as SIRT1 and Mfn2 prevents removal of dysfunctional mitochondria via mitophagy and proteasome digestion.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Removal of nuclei in muscle cells and motor neurons leads to fiber and motor neuron death and loss of innervation to the muscle cells.”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
- The authors state this as an assumption: Leaked mitochondrial contents initiate intrinsic apoptotic signaling leading to DNA fragmentation and nuclear apoptosis in a localized fiber region.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Aging increases mitochondrial stress that sensitizes the opening of the mitochondria transition permeability pore (mPTP).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
plaindirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“sarcopenia in aged humans and rodents is also associated with motor neuronal death (96, 139), which causes impaired innervation (48, 106), and a ~27% reduction in the motor unit pool.”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction
What the sources say
- Not checked yetcites [96] Mittal KR Logmani FH Age-related reduction in 8th cervical ventral nerve root myelinated fiber diameters and numbers in man J Gerontol 1987 42 8 10 3794203
- Not checked yetcites [139] Tomlinson BE Irving D The numbers of limb motor neurons in the human lumbosacral cord throughout life J Neurol. Sci 1977 34 213 219 925710
- Not checked yetcites [48] Hepple RT Rice CL Innervation and neuromuscular control in ageing skeletal muscle J Physiol 2016 594 1965 1978 26437581 PMC4933121
- Not checked yetcites [106] Pannerec A Springer M Migliavacca E Ireland A Piasecki M Karaz S Jacot G Metairon S Danenberg E Raymond F Descombes P McPhee JS Feige JN A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia Aging (Albany. NY) 2016 8 712 729 27019136 PMC4925824
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our current perspective and hypothesis is that mitochondrial deterioration in muscles and motor neurons is the primary initiator of sarcopenia (Figure 1).”
- Also stated in: § Mitochondrial regulation of sarcopenia - Hypothesis · plain
“Thus, mitochondria are key initiators and regulators of sarcopenia (Figure 1).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
- The authors state this as an assumption: Local mitochondrial damage causes increased mPTP opening.
- The authors state this as an assumption: mPTP opening triggers mitochondrial contents to leak into the cytosol.
- The authors state this as an assumption: Leaked mitochondrial contents initiate intrinsic apoptotic signaling leading to DNA fragmentation and nuclear apoptosis in a localized fiber region.
- Rests on an assumption: Aging suppression of autophagy activators such as SIRT1 and Mfn2 prevents removal of dysfunctional mitochondria via mitophagy and proteasome digestion.
- Also stated in: § Mitochondrial regulation of sarcopenia - Hypothesis · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Aging increases ROS production (22), and lowers antioxidant enzymes levels in muscle and neuron cells (58, 59, 121).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
What the sources say
- Not checked yetcites [22] Carter HN Chen CC Hood DA Mitochondria, muscle health, and exercise with advancing age Physiology. (Bethesda.) 2015 30 208 223 25933821
- Not checked yetcites [58] Jackson JR Ryan MJ Alway SE Long-term supplementation with resveratrol alleviates oxidative stress but does not attenuate sarcopenia in aged mice J Gerontol. A Biol. Sci Med. Sci 2011 66 751 764 21454355 PMC3143346
- Not checked yetcites [59] Jackson JR Ryan MJ Hao Y Alway SE Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats Am. J Physiol Regul. Integr. Comp Physiol 2010 299 R1572 R1581 20861279 PMC3007185
- Not checked yetcites [121] Ryan MJ Jackson JR Hao Y Leonard SS Alway SE Inhibition of xanthine oxidase reduces oxidative stress and improves skeletal muscle function in response to electrically stimulated isometric contractions in aged mice Free Radic. Biol. Med 2011 51 38 52 21530649 PMC3430730
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mitochondrial DNA (mtDNA) deletions or DNA mutations contribute to mitochondrial dysfunction and aging-related muscle fiber loss and atrophy (50, 90).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
What the sources say
- Not checked yetcites [50] Herbst A Wanagat J Cheema N Widjaja K McKenzie D Aiken JM Latent mitochondrial DNA deletion mutations drive muscle fiber loss at old age Aging Cell 2016 PMC5114866 27561813
- Not checked yetcites [90] McKenzie D Bua E McKiernan S Cao Z Aiken JM Mitochondrial DNA deletion mutations: a causal role in sarcopenia Eur. J Biochem 2002 269 2010 2015 11985577
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Leakage of the mitochondrial contents to the cell cytosol initiates death (apoptosis) signaling in muscle cells and motor neurons, which contributes to nuclear DNA fragmentation and if not repaired, nuclear apoptosis.”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
plaindirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds. It may state two separate claims as one.
- The authors state this as an assumption: mPTP opening triggers mitochondrial contents to leak into the cytosol.
- The authors state this as an assumption: Leaked mitochondrial contents initiate intrinsic apoptotic signaling leading to DNA fragmentation and nuclear apoptosis in a localized fiber region.
None of the sources cited for this claim have been checked yet.
In the paper
“Sarcopenia, is associated with increased levels of apoptosis (47) and reduced capabilities for muscle regeneration (41) leading to muscle wasting.”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction
What the sources say
- Not checked yetcites [47] Hao Y Jackson JR Wang Y Edens N Pereira SL Alway SE ß-Hydroxy-ß-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats Am. J. Physiol Regul. Integr. Comp Physiol 2011 301 R701 R715 21697520 PMC3174754
- Not checked yetcites [41] Garcia-Prat L Sousa-Victor P Munoz-Canoves P Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells FEBS J 2013 280 4051 4062 23452120 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Some denervated fibers become innervated by axons from surviving motor neurons (42, 45), whereas other fibers remain denervated and contribute to functional losses in sarcopenia (42).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction
What the sources say
- Not checked yetcites [42] Gilmore KJ Morat T Doherty TJ Rice CL Motor Unit Number Estimations and Neuromuscular Fidelity in Three Stages of Sarcopenia Muscle Nerve 2016 27576772
- Not checked yetcites [45] Gutmann E Hanzlikova V Denervation, reinnervation and regeneration of senile muscle Adv. Exp. Med Biol 1975 53 431 440 123404
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Opening the mPTP induces a further loss of mitochondrial membrane potential, and releases the mitochondrial contents to the cytosol to initiate apoptotic signaling (24, 77, 89).”
§ Mitochondria Initiate and Regulate Sarcopenia > Mitochondria permeability transition pore sensitization with aging – mitochondrial dysfunction
What the sources say
- Not checked yetcites [24] Chabi B Ljubicic V Menzies KJ Huang JH Saleem A Hood DA Mitochondrial function and apoptotic susceptibility in aging skeletal muscle Aging. Cell 2008 7 2 12 18028258 source
- Not checked yetcites [77] Leeuwenburgh C Gurley CM Strotman BA Dupont-Versteegden EE Age-related differences in apoptosis with disuse atrophy in soleus muscle Am. J Physiol Regul. Integr. Comp Physiol 2005 288 R1288 R1296 15650125
- Not checked yetcites [89] Marzetti E Wohlgemuth SE Lees HA Chung HY Giovannini S Leeuwenburgh C Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle Mech. Ageing. Dev 2008 129 542 549 18579179 PMC2585824 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a knockout of Mfn 1/2 in skeletal muscle, which prevented mitochondrial fusion, increased the accumulation of mtDNA defects and resulted in muscle atrophy (31).”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death > Altered mitochondrial dynamics with aging
What the sources say
- Not checked yetcites [31] Correia-Melo C Marques FD Anderson R Hewitt G Hewitt R Cole J Carroll BM Miwa S Birch J Merz A Rushton MD Charles M Jurk D Tait SW Czapiewski R Greaves L Nelson G Bohlooly Y Rodriguez-Cuenca S Vidal-Puig A Mann D Saretzki G Quarato G Green DR Adams PD von ZT Korolchuk VI Passos JF Mitochondria are required for pro-ageing features of the senescent phenotype EMBO J 2016 35 724 742 26848154 PMC4818766 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recent data by Sebastián and colleagues (127) show that Mfn2 declines in muscle with aging and loss of Mfn2 produces an aging-like phenotype, including age-associated mitochondrial dysfunction, higher ROS accumulation and muscle fiber atrophy.”
§ Mitochondria Initiate and Regulate Sarcopenia > Insufficient mitophagy allows unhealthy mitochondria to persist in aging muscles and neurons
What the sources say
- Not checked yetcites [127] Sebastian D Sorianello E Segales J Irazoki A Ruiz-Bonilla V Sala D Planet E Berenguer-Llergo A Munoz JP Sanchez-Feutrie M Plana N Hernandez-Alvarez MI Serrano AL Palacin M Zorzano A Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway EMBO J 2016 35 1677 1693 27334614 PMC4969577 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“other studies have found higher fusion profiles in muscles of humans (14), and prematurely aged mice (63), and larger mitochondria in muscles of old mice (75).”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death > Altered mitochondrial dynamics with aging
What the sources say
- Not checked yetcites [14] Bori Z Zhao Z Koltai E Fatouros IG Jamurtas AZ Douroudos II Terzis G Chatzinikolaou A Sovatzidis A Draganidis D Boldogh I Radak Z The effects of aging, physical training, and a single bout of exercise on mitochondrial protein expression in human skeletal muscle Exp. Gerontol 2012 47 417 424 22449457 PMC4915826
- Not checked yetcites [63] Joseph AM Adhihetty PJ Wawrzyniak NR Wohlgemuth SE Picca A Kujoth GC Prolla TA Leeuwenburgh C Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging PLoS. One 2013 8 e69327 23935986 PMC3720551 source
- Not checked yetcites [75] Leduc-Gaudet JP Picard M Jean PF St Sgarioto N Auger MJ Vallee J Robitaille R Pierre DH St Gouspillou G Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice Oncotarget 2015 6 17923 17937 26053100 PMC4627226 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“aging-induced mtDNA deletions are closely associated with a loss of mitochondrial function in motor neurons (123), neuronal malfunction in diseases like Parkinson’s disease (115), and muscle loss with aging (50, 91).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
What the sources say
- Not checked yetcites [123] Rygiel KA Grady JP Turnbull DM Respiratory chain deficiency in aged spinal motor neurons Neurobiol. Aging 2014 35 2230 2238 24684792 PMC4099519
- Not checked yetcites [115] Reeve A Meagher M Lax N Simcox E Hepplewhite P Jaros E Turnbull D The impact of pathogenic mitochondrial DNA mutations on substantia nigra neurons J Neurosci 2013 33 10790 10801 23804100 PMC6618501
- Not checked yetcites [50] Herbst A Wanagat J Cheema N Widjaja K McKenzie D Aiken JM Latent mitochondrial DNA deletion mutations drive muscle fiber loss at old age Aging Cell 2016 PMC5114866 27561813
- Not checked yetcites [91] McKiernan SH Colman R Lopez M Beasley TM Weindruch R Aiken JM Longitudinal analysis of early stage sarcopenia in aging rhesus monkeys Exp. Gerontol 2009 44 170 176 18983905 PMC2693938
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In neurons, DNA damage precedes neuronal apoptosis (85), whereas forced repair of DNA damage rescues neurons from elimination by apoptosis (86).”
§ Mitochondria Initiate and Regulate Sarcopenia > Introduction > Mitochondrial regulation of sarcopenia - Hypothesis
What the sources say
- Not checked yetcites [85] Martin LJ Liu Z Injury-induced spinal motor neuron apoptosis is preceded by DNA single-strand breaks and is p53- and Bax-dependent J Neurobiol 2002 50 181 197 11810634
- Not checked yetcites [86] Martin LJ Wong M Enforced DNA repair enzymes rescue neurons from apoptosis induced by target deprivation and axotomy in mouse models of neurodegeneration Mech. Ageing Dev 2016 PMC5192008 27364693
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“muscles of aged rodents and humans have a greater overall rate of fission vs. fusion (55, 62) and lower levels of the fusion protein Opa1 (62) as compared with younger muscles.”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death > Altered mitochondrial dynamics with aging
What the sources say
- Not checked yetcites [55] Ibebunjo C Chick JM Kendall T Eash JK Li C Zhang Y Vickers C Wu Z Clarke BA Shi J Cruz J Fournier B Brachat S Gutzwiller S Ma Q Markovits J Broome M Steinkrauss M Skuba E Galarneau JR Gygi SP Glass DJ Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia Mol. Cell Biol 2013 33 194 212 23109432 PMC3554128
- Not checked yetcites [62] Joseph AM Adhihetty PJ Buford TW Wohlgemuth SE Lees HA Nguyen LM Aranda JM Sandesara BD Pahor M Manini TM Marzetti E Leeuwenburgh C The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals Aging Cell 2012 11 801 809 22681576 PMC3444680 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“fiber atrophy and apoptotic signaling did not occur in other regions of the same muscle fibers that were located further away from the dysfunctional mitochondrial (26).”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death
What the sources say
- Not checked yetcites [26] Cheema N Herbst A McKenzie D Aiken JM Apoptosis and necrosis mediate skeletal muscle fiber loss in age-induced mitochondrial enzymatic abnormalities Aging Cell 2015 14 1085 1093 26365892 PMC4693455
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If the degenerative processes were not initiated locally but rather from a more general or systemic source, we would expect uniform muscle fiber wasting across its length, but this is not the case.”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cheema et al. (26) observed a localized aging-induced loss of the mitochondrial enzymes succinate dehydrogenase and cytochrome c oxidase. Interestingly, the same fiber region that had mitochondrial disruption was both atrophic and had high levels of the apoptotic protein caspase-3.”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death
What the sources say
- Not checked yetcites [26] Cheema N Herbst A McKenzie D Aiken JM Apoptosis and necrosis mediate skeletal muscle fiber loss in age-induced mitochondrial enzymatic abnormalities Aging Cell 2015 14 1085 1093 26365892 PMC4693455
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An acceleration of protein turnover with a net loss of protein is downstream of dysfunctional mitochondria but this represents a major contributor to sarcopenia.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“FOXOs control the mammalian target of rapamycin complex 1 (MTORC1) signaling, which is associated with muscle hypertrophy (43) and inhibition of mitophagy in skeletal muscle (23).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia
What the sources say
- Not checked yetcites [43] Goodman CA Frey JW Mabrey DM Jacobs BL Lincoln HC You JS Hornberger TA The role of skeletal muscle mTOR in the regulation of mechanical load-induced growth J Physiol 2011 589 5485 5501 21946849 PMC3240886
- Not checked yetcites [23] Castets P Ruegg MA MTORC1 determines autophagy through ULK1 regulation in skeletal muscle Autophagy 2013 9 1435 1437 23896646
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“when toxins or other compounds are injected into muscles, the compounds undergo retrograde transport to the neuromuscular junction (105), deposit in motor neurons (11), and sometimes contributes to motor neuronal dysfunction (reviewed in (33, 39).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > Communication between mitochondrial induced death signaling in muscle and motor neuron cells accelerate cell death in aging
What the sources say
- Not checked yetcites [105] Pamphlett R Bayliss A Lead uptake in motor axons Muscle Nerve 1992 15 620 625 1584254
- Not checked yetcites [11] Arvidson B Inorganic mercury is transported from muscular nerve terminals to spinal and brainstem motoneurons Muscle Nerve 1992 15 1089 1094 1383815
- Not checked yetcites [33] Deinhardt K Schiavo G Endocytosis and retrograde axonal traffic in motor neurons Biochem. Soc. Symp 2005 139 150 15649138
- Not checked yetcites [39] Garcia ML Fernandez A Solas MT Mitochondria, motor neurons and aging J Neurol. Sci 2013 330 18 26 23628465
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“spinal cord injury or denervation induces large-scale muscle wasting (57, 76, 107, 129, 131, 137), and denervation is a condition often seen as part of sarcopenia.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > Communication between mitochondrial induced death signaling in muscle and motor neuron cells accelerate cell death in aging
What the sources say
- Not checked yetcites [57] Iqbal S Ostojic O Singh K Joseph AM Hood DA Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse Muscle Nerve 2013 48 963 970 23494933 source
- Not checked yetcites [76] Lee G Lim JY Frontera WR Apoptosis in young and old denervated rat skeletal muscle Muscle Nerve 2016 27312511
- Not checked yetcites [107] Pelletier CA Miyatani M Giangregorio L Craven BC Sarcopenic Obesity in Adults With Spinal Cord Injury: A Cross-Sectional Study Arch. Phys. Med Rehabil 2016 97 1931 1937 27282328
- Not checked yetcites [129] Siu PM Alway SE Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle J. Physiol 2005 565 309 323 15774533 PMC1464486
- Not checked yetcites [131] Siu PM Alway SE Deficiency of the Bax gene attenuates denervation-induced apoptosis Apoptosis 2006 11 967 981 16763784 PMC4317263
- Not checked yetcites [137] Thakore NP Samantaray S Park S Nozaki K Smith JA Cox A Krause J Banik NL Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury Neurochem. Res 2016 41 44 52 26290268 PMC9727651
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PGC-1α2, PGC-1α3, and PGC-1α4, have been shown to stimulate protein synthesis and attenuate UPS activity in cultured myotubes and mouse skeletal muscle (87, 119).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > UPS disruption increases dysfunctional mitochondria in muscle and neural cells
What the sources say
- Not checked yetcites [87] Martinez-Redondo V Jannig PR Correia JC Ferreira DM Cervenka I Lindvall JM Sinha I Izadi M Pettersson-Klein AT Agudelo LZ Gimenez-Cassina A Brum PC Dahlman-Wright K Ruas JL Peroxisome Proliferator-activated Receptor gamma Coactivator-1 alpha Isoforms Selectively Regulate Multiple Splicing Events on Target Genes J Biol. Chem 2016 291 15169 15184 27231350 PMC4946932
- Not checked yetcites [119] Ruas JL White JP Rao RR Kleiner S Brannan KT Harrison BC Greene NP Wu J Estall JL Irving BA Lanza IR Rasbach KA Okutsu M Nair KS Yan Z Leinwand LA Spiegelman BM A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy Cell 2012 151 1319 1331 23217713 PMC3520615 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Activated SIRT1 deacetylates and activates PCG-1α which promotes mitochondria synthesis, assembly, growth and mitochondrial antioxidant production (54).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > Cross talk between mitochondrial regulators of autophagy and the UPS
What the sources say
- Not checked yetcites [54] Hsu CP Odewale I Alcendor RR Sadoshima J Sirt1 protects the heart from aging and stress Biol. Chem 2008 389 221 231 18208353
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Inhibition of MTORC1 in muscles of tuberous sclerosis complex (TSC) knockout mice, mimic many features of aging. This includes a loss of muscle mass and strength and attenuated mitophagy (23).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia
What the sources say
- Not checked yetcites [23] Castets P Ruegg MA MTORC1 determines autophagy through ULK1 regulation in skeletal muscle Autophagy 2013 9 1435 1437 23896646
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“MuRF-1 and MAFbx expression were reported to be lower in muscles of old rats than young adult rats (35) and not changed with aging in vastus lateralis of humans (145).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia
What the sources say
- Not checked yetcites [35] Edstrom E Altun M Hagglund M Ulfhake B Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle J Gerontol. A Biol. Sci Med Sci 2006 61 663 674 16870627
- Not checked yetcites [145] Whitman SA Wacker MJ Richmond SR Godard MP Contributions of the ubiquitin-proteasome pathway and apoptosis to human skeletal muscle wasting with age Pflugers Arch 2005 450 437 446 15952031
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“ubiquitin (17), 26S proteasome, poly-ubiquitinated proteins (3), MuRF-1 and MAFbx expression were all reported to be elevated in hindlimb muscles of sarcopenic rats as compared to young adult animals (3, 30).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia
What the sources say
- Not checked yetcites [17] Cai D Lee KK Li M Tang MK Chan KM Ubiquitin expression is up-regulated in human and rat skeletal muscles during aging Arch. Biochem. Biophys 2004 425 42 50 15081892
- Not checked yetcites [3] Altun M Besche HC Overkleeft HS Piccirillo R Edelmann MJ Kessler BM Goldberg AL Ulfhake B Muscle wasting in aged, sarcopenic rats is associated with enhanced activity of the ubiquitin proteasome pathway J Biol. Chem 2010 285 39597 39608 20940294 PMC3000941 source
- Not checked yetcites [30] Clavel S Coldefy AS Kurkdjian E Salles J Margaritis I Derijard B Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat Tibialis Anterior muscle Mech. Ageing Dev 2006 127 794 801 16949134
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AMPK activation (118) and the Forkhead box class O (FOXO) transcription factor family regulates the ubiquitin proteasome system (UPS), and the autophagy-lysosome system.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia
What the sources say
- Not checked yetcites [118] Romanello V Guadagnin E Gomes L Roder I Sandri C Petersen Y Milan G Masiero E Del PP Foretz M Scorrano L Rudolf R Sandri M Mitochondrial fission and remodelling contributes to muscle atrophy EMBO J 2010 29 1774 1785 20400940 PMC2876965 source
- Not checked yetcites [72] Koga H Kaushik S Cuervo AM Protein homeostasis and aging: The importance of exquisite quality control Ageing Res. Rev 2011 10 205 215 20152936 PMC2888802
- Not checked yetcites [74] Lecker SH Jagoe RT Gilbert A Gomes M Baracos V Bailey J Price SR Mitch WE Goldberg AL Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression FASEB J 2004 18 39 51 14718385
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“High levels of apoptotic signaling (1, 129) and altered autophagy signaling (102, 103) with elevated UPS activity (137) occurs in muscles after spinal cord injury or denervation.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > Communication between mitochondrial induced death signaling in muscle and motor neuron cells accelerate cell death in aging
What the sources say
- Not checked yetcites [1] Adhihetty PJ O'Leary MF Chabi B Wicks KL Hood DA Effect of denervation on mitochondrially mediated apoptosis in skeletal muscle J. Appl. Physiol 2007 102 1143 1151 17122379 source
- Not checked yetcites [129] Siu PM Alway SE Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle J. Physiol 2005 565 309 323 15774533 PMC1464486
- Not checked yetcites [102] O'Leary MF Vainshtein A Carter HN Zhang Y Hood DA Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals Am. J Physiol Cell Physiol 2012 303 C447 C454 22673615
- Not checked yetcites [103] O'Leary MF Vainshtein A Iqbal S Ostojic O Hood DA Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle Am. J Physiol Cell Physiol 2013 304 C422 C430 23220115 source
- Not checked yetcites [137] Thakore NP Samantaray S Park S Nozaki K Smith JA Cox A Krause J Banik NL Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury Neurochem. Res 2016 41 44 52 26290268 PMC9727651
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Deacetylation of FOXO1 and FOXO3a by SIRT1 (19, 20) mediates autophagic signaling in muscle cells, and aging attenuates SIRT1, which reduces autophagy (134).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > Cross talk between mitochondrial regulators of autophagy and the UPS
What the sources say
- Not checked yetcites [19] Canto C Gerhart-Hines Z Feige JN Lagouge M Noriega L Milne JC Elliott PJ Puigserver P Auwerx J AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity Nature 2009 458 1056 1060 19262508 PMC3616311 source
- Not checked yetcites [20] Canto C Jiang LQ Deshmukh AS Mataki C Coste A Lagouge M Zierath JR Auwerx J Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle Cell Metab 2010 11 213 219 20197054 PMC3616265 source
- Not checked yetcites [134] Tang AH Rando TA Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation EMBO J 2014 33 2782 2797 25316028 PMC4282556
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“High ROS can damage more mitochondria in muscle and neurons (81) and potentially elevate ROS levels even higher.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > UPS disruption increases dysfunctional mitochondria in muscle and neural cells
What the sources say
- Not checked yetcites [81] Maharjan S Oku M Tsuda M Hoseki J Sakai Y Mitochondrial impairment triggers cytosolic oxidative stress and cell death following proteasome inhibition Sci. Rep 2014 4 5896 25077633 PMC4116626
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The discrepancy between these studies might be due to variability introduced by a low number of subjects or animals in each study, and perhaps by some differences in the age and sex of the subjects that were studied.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“motor neuron dysfunction and death may converge upon mitochondria, and mitochondrial dynamics may play an important role in regulation of neuronal function that contributes to accelerated sarcopenia.”
§ Mitochondria Initiate and Regulate Sarcopenia > Local apoptotic signaling in aging muscles and motor neurons becomes more wide spread to result in cell death > Altered mitochondrial dynamics with aging
What the sources say
- Not checked yetcites [61] Jiang Z Wang W Perry G Zhu X Wang X Mitochondrial dynamic abnormalities in amyotrophic lateral sclerosis Transl. Neurodegener 2015 4 14 26225210 PMC4518588
- Not checked yetcites [143] Wang W Zhang F Li L Tang F Siedlak SL Fujioka H Liu Y Su B Pi Y Wang X MFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons J Biol. Chem 2015 290 168 182 25416777 PMC4281719
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PARK7 is an antioxidant protein that limits mitochondrial damage in response to oxidative stress (12) and it regulates skeletal muscle contractile protein synthesis and hypertrophy (149).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > How might exercise target dysfunctional mitochondria by mitophagy?
What the sources say
- Not checked yetcites [12] Billia F Hauck L Grothe D Konecny F Rao V Kim RH Mak TW Parkinson-susceptibility gene DJ-1/PARK7 protects the murine heart from oxidative damage in vivo Proc. Natl. Acad. Sci U. S. A 2013 110 6085 6090 23530187 PMC3625258
- Not checked yetcites [149] Yu H Waddell JN Kuang S Bidwell CA Park7 expression influences myotube size and myosin expression in muscle PLoS. One 2014 9 e92030 24637782 PMC3956870
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“We know that exercise downregulates apoptosis and upregulates mitophagy (4, 52, 128, 146).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > The potential role for mitochondrial biogenesis to reduce sarcopenia
What the sources say
- Not checked yetcites [4] Alway SE Bennett BT Wilson JC Sperringer J Mohamed JS Edens NK Pereira SL Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats J. App. Physiol 2015 118 319 330 PMC4312851 25414242
- Not checked yetcites [52] Hood DA Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle Appl Physiol Nutr Metab 2009 34 465 472 19448716
- Not checked yetcites [128] Sin TK Yu AP Yung BY Yip SP Chan LW Wong CS Rudd JA Siu PM Effects of long-term resveratrol-induced SIRT1 activation on insulin and apoptotic signalling in aged skeletal muscle Acta Diabetol 2015 52 1063 1075 25959421
- Not checked yetcites [146] Wohlgemuth SE Seo AY Marzetti E Lees HA Leeuwenburgh C Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise Exp. Gerontol 2010 45 138 148 19903516 PMC2829942 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“If the same processes occur in humans as is the case in rodents and non-human mammals (64), exercise, or nutritional intervention such as caloric restriction would also be expected to increase mitophagy removal of dysfunctional mitochondrial, so the mitochondria that remain are proportionally healthier (64).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > How might exercise target dysfunctional mitochondria by mitophagy?
What the sources say
- Not checked yetcites [64] Joseph AM Malamo AG Silvestre J Wawrzyniak N Carey-Love S Nguyen LM Dutta D Xu J Leeuwenburgh C Adhihetty PJ Short-term caloric restriction, resveratrol, or combined treatment regimens initiated in late-life alter mitochondrial protein expression profiles in a fiber-type specific manner in aged animals Exp. Gerontol 2013 48 858 868 23747682 PMC4550205
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Aging causes degradation and availability of LAMP2A in the lysosomal membranes (69), which reduces the effectiveness of CMA.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > How might exercise target dysfunctional mitochondria by mitophagy?
What the sources say
- Not checked yetcites [69] Kiffin R Kaushik S Zeng M Bandyopadhyay U Zhang C Massey AC Martinez-Vicente M Cuervo AM Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age J Cell Sci 2007 120 782 791 17284523
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“satellite cells are affected adversely by aging, mitochondrial damage and death signaling (4, 6, 7, 144)”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > The potential role for mitochondrial biogenesis to reduce sarcopenia
What the sources say
- Not checked yetcites [4] Alway SE Bennett BT Wilson JC Sperringer J Mohamed JS Edens NK Pereira SL Green tea extract attenuates muscle loss and improves muscle function during disuse, but fails to improve muscle recovery following unloading in aged rats J. App. Physiol 2015 118 319 330 PMC4312851 25414242
- Not checked yetcites [6] Alway SE Myers MJ Mohamed JS Regulation of satellite cell function in sarcopenia Frontiers of Aging Neuroscience 2014 6 1 15 PMC4170136 25295003
- Not checked yetcites [7] Alway SE Pereira SL Edens NK Hao Y Bennett BT β−Hydroxy-β-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy Exp. Gerontol 2013 48 973 984 23832076
- Not checked yetcites [144] Wang X Pickrell AM Rossi SG Pinto M Dillon LM Hida A Rotundo RL Moraes CT Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cell pool Hum. Mol. Genet 2013 22 3976 3986 23760083 PMC3766186
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both endurance and resistance exercise have been associated with elevated mitochondrial biogenesis (93, 109).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > The potential role for mitochondrial biogenesis to reduce sarcopenia
What the sources say
- Not checked yetcites [93] Menzies KJ Singh K Saleem A Hood DA Sirtuin 1-mediated effects of exercise and resveratrol on mitochondrial biogenesis J Biol. Chem 2013 288 6968 6979 23329826 PMC3591607
- Not checked yetcites [109] Porter C Reidy PT Bhattarai N Sidossis LS Rasmussen BB Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle Med Sci Sports Exerc 2015 47 1922 1931 25539479 PMC4478283 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“it has been proposed that autophagy signals are necessary to achieve aerobic improvements in skeletal muscle (78).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > How might exercise target dysfunctional mitochondria by mitophagy?
What the sources say
- Not checked yetcites [78] Lira VA Okutsu M Zhang M Greene NP Laker RC Breen DS Hoehn KL Yan Z Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance FASEB J 2013 27 4184 4193 23825228 PMC4046188 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Exercise-induced Pink1 activation of Drp1 (112) could also target dysfunctional mitochondria for mitophagy.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > How might exercise target dysfunctional mitochondria by mitophagy?
What the sources say
- Not checked yetcites [112] Pryde KR Smith HL Chau KY Schapira AH PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy J Cell Biol 2016 213 163 171 27091447 PMC5084273 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Overexpression of PARK7 reduces mitochondrial dysfunction under oxidative stress (142) which shows a direct link between autophagy and mitochondrial function.”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > How might exercise target dysfunctional mitochondria by mitophagy?
What the sources say
- Not checked yetcites [142] Wang B Cai Z Tao K Zeng W Lu F Yang R Feng D Gao G Yang Q Essential control of mitochondrial morphology and function by chaperone-mediated autophagy through degradation of PARK7 Autophagy 2016 1 14 27171370 PMC4968227
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“we would expect that altered neuronal signaling is due at least in part to high ROS production and mitochondrial dysfunction in the muscle cells, and conversely, that neural dysfunction will be communicated to muscle cells (57, 100).”
§ Mitochondria Initiate and Regulate Sarcopenia > FOXO proteins and the ubiquitin proteasome system (UPS) in muscle atrophy and sarcopenia > Communication between mitochondrial induced death signaling in muscle and motor neuron cells accelerate cell death in aging
What the sources say
- Not checked yetcites [57] Iqbal S Ostojic O Singh K Joseph AM Hood DA Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse Muscle Nerve 2013 48 963 970 23494933 source
- Not checked yetcites [100] Muller FL Song W Jang YC Liu Y Sabia M Richardson A Van Remmen H Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production Am. J. Physiol. Regul. Integr. Comp. Physiol 2007 293 R1159 R1168 17584954
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Proteasome activation leads to removal of cellular contents close to the site of dysfunctional mitochondria”
§ Mitochondria Initiate and Regulate Sarcopenia > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The authors state this as an assumption.
Local mitochondrial damage causes increased mPTP opening.
“This model assumes that local mitochondrial damage (potentially via ROS, high calcium loads, mtDNA damage etc.) causes increased mPTP opening”
The authors state this as an assumption.
mPTP opening triggers mitochondrial contents to leak into the cytosol.
“which triggers the contents of the mitochondria to leak to the cytosol.”
The authors state this as an assumption.
Leaked mitochondrial contents initiate intrinsic apoptotic signaling leading to DNA fragmentation and nuclear apoptosis in a localized fiber region.
“This initiates the intrinsic apoptotic signaling pathway leading to DNA fragmentation and nuclear apoptosis in a localized region of the fiber.”
The paper relies on this without support.
Aging suppression of autophagy activators such as SIRT1 and Mfn2 prevents removal of dysfunctional mitochondria via mitophagy and proteasome digestion.
“An aging-suppression of autophagy activators like Sirtuin 1 (SIRT1) and Mfn2 or other proteins involved in mitophagy, prevents removal of dysfunctional mitochondria via mitophagy and proteasome digestion.”
The paper relies on this without support.
Fragmented mitochondria have lower respiratory capacity and greater ROS production, increasing susceptibility to release contents and activate the intrinsic caspase apoptotic pathway.
“Fragmented mitochondria tend to have a lower respiratory capacity, and a greater production of ROS, which increases the susceptibility of mitochondria to release its contents and activate the intrinsic caspase apoptotic pathway.”
The paper relies on this without support.
Aging is associated with high cellular ROS levels, and ROS accumulation induces mPTP opening.
“aging is associated with high cell levels of ROS and ROS accumulation is an inductor for mPTP opening.”
The paper relies on this without support.
Aging leads to systemic mitochondrial dysfunction throughout the body, possibly caused by high ROS or mtDNA damage accumulation.
“Although aging induces wide spread systemic mitochondrial dysfunction, perhaps as a result of high ROS or accumulation of mtDNA damage”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“mitochondrial dysfunction (14) are the crucial factors accountable for this pathology.”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [14]
In the citing paper
“Figure 1 shows the general pathways initiated by mitochondrial alteration resulting in motor neuron and muscle cell death and culminating in sarcopenia (14).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [14]
In the citing paper
“mitophagy, as a kind of selective autophagy, can identify and degrade damaged and dysfunctional mitochondria, thus generating a self-protective coping mechanism against mitochondrial dysfunction [47]”
From Lifelong Aerobic Exercise Alleviates Sarcopenia by Activating Autophagy and Inhibiting Protein Degradation via the AMPK/PGC-1α Signaling Pathway (2021) · cites this paper as [47]
Citations
Cites
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., & Goldberg, A. L. (2004) · The FASEB Journal · doi:10.1096/fj.03-0610com · Cited by 1,539
Autophagy maintains stemness by preventing senescence
García-Prat, L., Martínez-Vicente, M., Perdiguero, E., Ortet, L., Rodríguez-Ubreva, J., Rebollo, E., Ruiz-Bonilla, V., Gutarra, S., Ballestar, E., Serrano, A. L., et al. (2016) · Nature · doi:10.1038/nature16187 · Cited by 1,355 · cited 2×
“MITOCHONDRIAL PERMEABILITY TRANSITION PORE SENSITIZATION WITH AGING — MITOCHONDRIAL DYSFUNCTION Stress-induced damage to mitochondrial membranes (40,108,144,147) contributes to sensitization of the mitochondrial permeability transition pore (44).”
BackgroundPINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria
Chen, Y., & Dorn, G. W. (2013) · Science · doi:10.1126/science.1231031 · Cited by 1,323 · cited 1×
“Mitofusin 2 (Mfn2) has an important role regulating mitochondrial fusion, but it also acts as a receptor for Pink1 and Parkin-targeted mitophagy (27).”
BackgroundBrand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063 · cited 2×
“Copyright © 2017 by the American College of Sports Medicin potential to damage cellular mitochondria (reviewed in (15)).”
BackgroundSandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z. P., Lecker, S. H., Goldberg, A. L., & Spiegelman, B. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607795103 · Cited by 974 · cited 1×
“Furthermore, PGC-1α reduces muscle protein degradation by the UPS via blocking nuclear factor κB and FoxO3 activity (16,124).”
BackgroundCantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., Zierath, J. R., & Auwerx, J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.006 · Cited by 921 · cited 14×
“AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) trigger the destruction of dysfunctional fragmented mitochondria through FoxO3-dependent autophagy (mitophagy) (94,118).”
BackgroundInfluentialSlowing ageing by design: the rise of NAD+ and sirtuin-activating compounds
Bonkowski, M. S., & Sinclair, D. A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.93 · Cited by 834 · cited 1×
“SIRT1 is important for deacetylation of mitochondrial-interacting targets like PGC-1α, FOXO3, p53, and NF-kB (reviewed in (13,110) and has been implicated in improving function and life span in aging (95).”
BackgroundMitochondria are required for pro-ageing features of the senescent phenotype
Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592862 · Cited by 796 · cited 2×
“Mitochondrial stress in aging can originate from greater levels of oxidants, DNA damage, or denervation (31,133).”
BackgroundSIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks
Rardin, M. J., He, W., Nishida, Y., Newman, J. C., Carrico, C., Danielson, S. R., Guo, A., Gut, P., Sahu, A. K., Li, B., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.11.013 · Cited by 711 · cited 1×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundMilan, G., Romanello, V., Pescatore, F., Armani, A., Paik, J.-H., Frasson, L., Seydel, A., Zhao, J., Abraham, R., Goldberg, A. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms7670 · Cited by 709 · cited 1×
“AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) trigger the destruction of dysfunctional fragmented mitochondria through FoxO3-dependent autophagy (mitophagy) (94,118).”
BackgroundA PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy
Ruas, J. L., White, J. P., Rao, R. R., Kleiner, S., Brannan, K. T., Harrison, B. C., Greene, N. P., Wu, J., Estall, J. L., Irving, B. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.050 · Cited by 677 · cited 1×
“PGC-1α2, PGC-1α3, and PGC-1α4 have been shown to stimulate protein synthesis and attenuate UPS activity in cultured myotubes and mouse skeletal muscle (87,119).”
BackgroundThe numbers of limb motor neurons in the human lumbosacral cord throughout life
Tomlinson, B. E., & Irving, D. (1977) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(77)90069-7 · Cited by 602 · cited 1×
“However, sarcopenia in aged humans and rodents also is associated with motor neuronal death (96,139), which causes impaired innervation (48,106), and a ~27% reduction in the motor unit pool.”
BackgroundMitochondrial fission and remodelling contributes to muscle atrophy
Romanello, V., Guadagnin, E., Gomes, L., Roder, I., Sandri, C., Petersen, Y., Milan, G., Masiero, E., Del Piccolo, P., Foretz, M., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.60 · Cited by 596 · cited 2×
“AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) trigger the destruction of dysfunctional fragmented mitochondria through FoxO3-dependent autophagy (mitophagy) (94,118).”
BackgroundHafner, A. V., Dai, J., Gomes, A. P., Xiao, C., Palmeira, C. M., Rosenzweig, A., & Sinclair, D. A. (2010) · Aging · doi:10.18632/aging.100252 · Cited by 554 · cited 4×
“Proteins like SIRT1 and SIRT3 may be important regulators of deacetylation in mitochondria (46,97,132).”
BackgroundInfluentialProtein Homeostasis and Aging: the importance of exquisite quality control
Koga, H., Kaushik, S., & Cuervo, A. M. (2011) · Ageing research reviews · doi:10.1016/j.arr.2010.02.001 · Cited by 476 · cited 1×
“FOXO proteins also regulate the UPS, which is a tightly regulated system responsible for normal intracellular protein turnover and elimination of misfolded and dysfunctional proteins (72,74).”
BackgroundMitochondrial function and apoptotic susceptibility in aging skeletal muscle
Chabi, B., Ljubicic, V., Menzies, K. J., Huang, J. H., Saleem, A., & Hood, D. A. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2007.00347.x · Cited by 437 · cited 1×
“Opening the mPTP induces a further loss of mitochondrial membrane potential and releases the mitochondrial contents to the cytosol to initiate apoptotic signaling (24,77,89).”
BackgroundLira, V. A., Okutsu, M., Zhang, M., Greene, N. P., Laker, R. C., Breen, D. S., Hoehn, K. L., & Yan, Z. (2013) · The FASEB Journal · doi:10.1096/fj.13-228486 · Cited by 432 · cited 2×
“Indeed, it has been proposed that autophagy signals are necessary to achieve aerobic improvements in skeletal muscle (78).”
BackgroundRyanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging
Andersson, D. C., Betzenhauser, M. J., Reiken, S., Meli, A. C., Umanskaya, A., Xie, W., Shiomi, T., Zalk, R., Lacampagne, A., & Marks, A. R. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.05.014 · Cited by 424 · cited 1×
“mPTP opening is further exacerbated by an imbalance of Ca homeostasis that likely results from leaky ryanodine receptors in aged skeletal muscle (10).”
BackgroundInnervation and neuromuscular control in ageing skeletal muscle
Hepple, R. T., & Rice, C. L. (2015) · The Journal of Physiology · doi:10.1113/jp270561 · Cited by 417 · cited 2×
“However, sarcopenia in aged humans and rodents also is associated with motor neuronal death (96,139), which causes impaired innervation (48,106), and a ~27% reduction in the motor unit pool.”
BackgroundIntracellular signaling during skeletal muscle atrophy
Kandarian, S. C., & Jackman, R. W. (2005) · Muscle & Nerve · doi:10.1002/mus.20442 · Cited by 405
The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet
Mitchell, S. J., Martín‐Montalvo, A., Mercken, E. M., Palacios, H. H., Ward, T. M., Abulwerdi, G. A., Minor, R. K., Vlasuk, G. P., Ellis, J. L., Sinclair, D. A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.031 · Cited by 402 · cited 1×
“SIRT1 is important for deacetylation of mitochondrial-interacting targets like PGC-1α, FOXO3, p53, and NF-kB (reviewed in (13,110) and has been implicated in improving function and life span in aging (95).”
BackgroundWohlgemuth, S. E., Seo, A. Y., Marzetti, E., Lees, H. A., & Leeuwenburgh, C. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2009.11.002 · Cited by 397 · cited 1×
“We know that exercise downregulates apoptosis and upregulates mitophagy (4,52,128,146).”
BackgroundSebastián, D., Sorianello, E., Segalés, J., Irazoki, A., Ruiz‐Bonilla, V., Sala, D., Planet, E., Berenguer‐Llergo, A., Muñoz, J. P., Sánchez‐Feutrie, M., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201593084 · Cited by 396 · cited 2×
“(127) show that Mfn2 declines in muscle with aging, and loss of Mfn2 produces an aging-like phenotype, including age-associated mitochondrial dysfunction, higher ROS accumulation, and muscle fiber atrophy.”
BackgroundJoseph, A., Adhihetty, P. J., Buford, T. W., Wohlgemuth, S. E., Lees, H. A., Nguyen, L. M. ‐., Aranda, J. M., Sandesara, B. D., Pahor, M., Manini, T. M., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00844.x · Cited by 395 · cited 3×
“Consistent with the fragmented mitochondrial phenotype in muscles from old hosts, there is evidence to suggest that muscles of aged rodents and humans have a greater overall rate of fission versus fusion (55,62) and lower levels of the fusion protein Opa1 (62) as compared with younger muscles.”
BackgroundApoptosis in skeletal muscle with aging
Dirks, A., & Leeuwenburgh, C. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00458.2001 · Cited by 377 · cited 1×
“Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents (4,7,26,34,47,77,88,130) and humans (44,145).”
BackgroundMitochondrial and nuclear DNA matching shapes metabolism and healthy ageing
Latorre-Pellicer, A., Moreno-Loshuertos, R., Lechuga-Vieco, A. V., Sánchez-Cabo, F., Torroja, C., Acín-Pérez, R., Calvo, E., Aix, E., González-Guerra, A., Logan, A., et al. (2016) · Nature · doi:10.1038/nature18618 · Cited by 377 · cited 2×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundCheng, A., Yang, Y., Zhou, Y., Maharana, C., Lu, D., Peng, W., Liu, Y., Wan, R., Marosi, K., Misiak, M., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.013 · Cited by 371 · cited 2×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundMuller, F. L., Song, W., Jang, Y. C., Liu, Y., Sabia, M., Richardson, A., & Van Remmen, H. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00767.2006 · Cited by 355 · cited 1×
“Thus, we would expect that altered neuronal signaling is due at least in part to high ROS production and mitochondrial dysfunction in the muscle cells, and conversely, that neural dysfunction will be communicated to muscle cells (57,100).”
BackgroundMitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
Calvani, R., Joseph, A.-M., Adhihetty, P. J., Miccheli, A., Bossola, M., Leeuwenburgh, C., Bernabei, R., & Marzetti, E. (2013) · bchm · doi:10.1515/hsz-2012-0247 · Cited by 328 · cited 1×
“It is interesting that a loss of mitochondria function with aging is a mechanism that is shared by both muscle cells (18,63) and motor neurons (123).”
BackgroundWu, J., Quijano, C., Chen, E., Liu, H., Cao, L., Fergusson, M. M., Rovira, I. I., Gutkind, S., Daniels, M. P., Komatsu, M., et al. (2009) · Aging · doi:10.18632/aging.100038 · Cited by 311 · cited 1×
“MITOCHONDRIAL PERMEABILITY TRANSITION PORE SENSITIZATION WITH AGING — MITOCHONDRIAL DYSFUNCTION Stress-induced damage to mitochondrial membranes (40,108,144,147) contributes to sensitization of the mitochondrial permeability transition pore (44).”
BackgroundThe role of skeletal muscle mTOR in the regulation of mechanical load‐induced growth
Goodman, C. A., Frey, J. W., Mabrey, D. M., Jacobs, B. L., Lincoln, H. C., You, J., & Hornberger, T. A. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.218255 · Cited by 297 · cited 1×
“FOXOs control the mammalian target of rapamycin complex 1 (MTORC1) signaling, which is associated with muscle hypertrophy (43) and inhibition of mitophagy in skeletal muscle (23).”
BackgroundInduction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation
Tang, A. H., & Rando, T. A. (2014) · The EMBO Journal · doi:10.15252/embj.201488278 · Cited by 294 · cited 1×
“Deacetylation of FOXO1 and FOXO3a by SIRT1 (19,20) mediates autophagic signaling in muscle cells, and aging attenuates SIRT1, which reduces autophagy (134).”
BackgroundResistance exercise training alters mitochondrial function in human skeletal muscle
PORTER, C., REIDY, P. T., BHATTARAI, N., SIDOSSIS, L. S., & RASMUSSEN, B. B. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000605 · Cited by 288 · cited 1×
“Both endurance and resistance exercise have been associated with elevated mitochondrial biogenesis (93,109).”
BackgroundMitochondrial morphology is altered in atrophied skeletal muscle of aged mice
Leduc-Gaudet, J.-P., Picard, M., Pelletier, F. S.-J., Sgarioto, N., Auger, M.-J., Vallée, J., Robitaille, R., St-Pierre, D. H., & Gouspillou, G. (2015) · Oncotarget · doi:10.18632/oncotarget.4235 · Cited by 273 · cited 4×
“However, it should be pointed out that other evidence does not support a decrease in Mfn2 or a decrease in the Mfn2-to-Drp1 ratio that would be expected if Mfn2 were suppressed in muscles of aged mice (75).”
BackgroundResultInfluentialThe role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass
Rom, O., & Reznick, A. Z. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.12.031 · Cited by 271 · cited 1×
“FOXOs activate lysosomal cathepsins and cytosolic protease calpains, which progress toward ATP-dependent UPS activation via FOXO3aassociated MuRF-1 and MAFbx regulation (reviewed in (66,117)).”
BackgroundIbebunjo, C., Chick, J. M., Kendall, T., Eash, J. K., Li, C., Zhang, Y., Vickers, C., Wu, Z., Clarke, B. A., Shi, J., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01036-12 · Cited by 267
Hood, D. A. (2009) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h09-045 · Cited by 242 · cited 1×
“We know that exercise downregulates apoptosis and upregulates mitophagy (4,52,128,146).”
BackgroundEffect of denervation on mitochondrially mediated apoptosis in skeletal muscle.
Adhihetty, P. J., O'Leary, M. F. N., Chabi, B., Wicks, K. L., & Hood, D. A. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00768.2006 · Cited by 240 · cited 1×
“High levels of apoptotic signaling (1,129) and altered autophagy signaling (102,103) with elevated UPS activity (137) occur in muscles after spinal cord injury or denervation.”
BackgroundSirtuin regulation in aging and injury
Poulose, N., & Raju, R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.017 · Cited by 236 · cited 1×
“SIRT1 is important for deacetylation of mitochondrial-interacting targets like PGC-1α, FOXO3, p53, and NF-kB (reviewed in (13,110) and has been implicated in improving function and life span in aging (95).”
BackgroundClavel, S., Coldefy, A.-S., Kurkdjian, E., Salles, J., Margaritis, I., & Dérijard, B. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.07.005 · Cited by 233 · cited 1×
“For example, ubiquitin (17), 26S proteasome, polyubiquitinated proteins (3), MuRF-1, and MAFbx expression were all reported to be elevated in hindlimb muscles of sarcopenic rats as compared with young adult animals (3,30).”
BackgroundAge-related differences in apoptosis with disuse atrophy in soleus muscle
Leeuwenburgh, C., Gurley, C. M., Strotman, B. A., & Dupont-Versteegden, E. E. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00576.2004 · Cited by 231 · cited 2×
“Opening the mPTP induces a further loss of mitochondrial membrane potential and releases the mitochondrial contents to the cytosol to initiate apoptotic signaling (24,77,89).”
BackgroundAltun, M., Besche, H. C., Overkleeft, H. S., Piccirillo, R., Edelmann, M. J., Kessler, B. M., Goldberg, A. L., & Ulfhake, B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129718 · Cited by 226 · cited 1×
“For example, ubiquitin (17), 26S proteasome, polyubiquitinated proteins (3), MuRF-1, and MAFbx expression were all reported to be elevated in hindlimb muscles of sarcopenic rats as compared with young adult animals (3,30).”
BackgroundFerri, A., Sanes, J. R., Coleman, M. P., Cunningham, J. M., & Kato, A. C. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00206-9 · Cited by 221 · cited 1×
“Furthermore, inhibition of synaptic loss reduces apoptosis of motor neurons in amousemodel ofmotor neuron disease (37).”
BackgroundBrault, J. J., Jespersen, J. G., & Goldberg, A. L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.113092 · Cited by 217 · cited 1×
“Furthermore, PGC-1α reduces muscle protein degradation by the UPS via blocking nuclear factor κB and FoxO3 activity (16,124).”
BackgroundGouspillou, G., Sgarioto, N., Kapchinsky, S., Purves‐Smith, F., Norris, B., Pion, C. H., Barbat‐Artigas, S., Lemieux, F., Taivassalo, T., Morais, J. A., et al. (2014) · The FASEB Journal · doi:10.1096/fj.13-242750 · Cited by 217 · cited 2×
“MITOCHONDRIAL PERMEABILITY TRANSITION PORE SENSITIZATION WITH AGING — MITOCHONDRIAL DYSFUNCTION Stress-induced damage to mitochondrial membranes (40,108,144,147) contributes to sensitization of the mitochondrial permeability transition pore (44).”
BackgroundMitochondria-associated apoptotic signalling in denervated rat skeletal muscle
Siu, P. M., & Alway, S. E. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.081083 · Cited by 216
Self-citationAltered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age
Kiffin, R., Kaushik, S., Zeng, M., Bandyopadhyay, U., Zhang, C., Massey, A. C., Martinez-Vicente, M., & Cuervo, A. M. (2007) · Journal of Cell Science · doi:10.1242/jcs.001073 · Cited by 213 · cited 1×
“Aging causes degradation and availability of LAMP2A in the lysosomal membranes (69), which reduces the effectiveness of CMA.”
BackgroundMaharjan, S., Oku, M., Tsuda, M., Hoseki, J., & Sakai, Y. (2014) · Scientific Reports · doi:10.1038/srep05896 · Cited by 212 · cited 2×
“High ROS can damage more mitochondria in muscle and neurons (81) and potentially elevate ROS levels even higher.”
BackgroundHerbst, A., Pak, J. W., McKenzie, D., Bua, E., Bassiouni, M., & Aiken, J. M. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.3.235 · Cited by 200
Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle
Edstrom, E., Altun, M., Hagglund, M., & Ulfhake, B. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.7.663 · Cited by 196 · cited 1×
“In contrast, MuRF-1 andMAFbx expression were reported to be lower in muscles of old rats than young adult rats (35) and not changed with aging in the vastus lateralis of humans (145).”
BackgroundMitochondria, Muscle Health, and Exercise with Advancing Age
Carter, H. N., Chen, C. C. W., & Hood, D. A. (2015) · Physiology · doi:10.1152/physiol.00039.2014 · Cited by 191 · cited 2×
“Aging increases reactive oxygen species (ROS)–induced production (22) and lowers antioxidant enzyme levels in muscle and neuron cells (58,59,121).”
BackgroundPink1 regulates the oxidative phosphorylation machinery via mitochondrial fission
Liu, W., Acín-Peréz, R., Geghman, K. D., Manfredi, G., Lu, B., & Li, C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1107332108 · Cited by 190 · cited 3×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundPink1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy
Pryde, K. R., Smith, H. L., Chau, K.-Y., & Schapira, A. H. V. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201509003 · Cited by 185 · cited 4×
“However, it should be pointed out that other evidence does not support a decrease in Mfn2 or a decrease in the Mfn2-to-Drp1 ratio that would be expected if Mfn2 were suppressed in muscles of aged mice (75).”
BackgroundInfluentialMarzetti, E., Wohlgemuth, S. E., Lees, H. A., Chung, H.-Y., Giovannini, S., & Leeuwenburgh, C. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.05.005 · Cited by 172 · cited 1×
“Opening the mPTP induces a further loss of mitochondrial membrane potential and releases the mitochondrial contents to the cytosol to initiate apoptotic signaling (24,77,89).”
BackgroundSirtuin 1-mediated Effects of Exercise and Resveratrol on Mitochondrial Biogenesis
Menzies, K. J., Singh, K., Saleem, A., & Hood, D. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.431155 · Cited by 171 · cited 1×
“Both endurance and resistance exercise have been associated with elevated mitochondrial biogenesis (93,109).”
BackgroundIqbal, S., Ostojic, O., Singh, K., Joseph, A., & Hood, D. A. (2013) · Muscle & Nerve · doi:10.1002/mus.23838 · Cited by 169 · cited 6×
“However, mitochondria can range from small individual organelles to rather extensive and connected reticular systems (57).”
BackgroundResultInfluentialAdaptive plasticity of autophagic proteins to denervation in aging skeletal muscle
O'Leary, M. F., Vainshtein, A., Iqbal, S., Ostojic, O., & Hood, D. A. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00240.2012 · Cited by 165 · cited 3×
“Nevertheless, an accumulation of lipofuscin granules suggests a failure of the lysosome to remove dysfunctional mitochondrial in aging even when Parkin has translocated to the mitochondria (103).”
BackgroundRegulation of Satellite Cell Function in Sarcopenia
Alway, S. E., Myers, M. J., & Mohamed, J. S. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00246 · Cited by 163 · cited 1×
“In the quest to attenuate sarcopenia, it also will be important to understand the limit for mitochondrial health to impact satellite cell function for repairing and replacing sections of fibers or whole fibers because satellite cells are affected adversely by aging, mitochondrial damage, and death signaling (4,6,7,144…”
BackgroundSelf-citationJoseph, A.-M., Adhihetty, P. J., Wawrzyniak, N. R., Wohlgemuth, S. E., Picca, A., Kujoth, G. C., Prolla, T. A., & Leeuwenburgh, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069327 · Cited by 161 · cited 5×
“It is interesting that a loss of mitochondria function with aging is a mechanism that is shared by both muscle cells (18,63) and motor neurons (123).”
BackgroundResultInfluentialWhitman, S. A., Wacker, M. J., Richmond, S. R., & Godard, M. P. (2005) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-005-1473-8 · Cited by 156 · cited 2×
“In contrast, MuRF-1 andMAFbx expression were reported to be lower in muscles of old rats than young adult rats (35) and not changed with aging in the vastus lateralis of humans (145).”
BackgroundMitochondrial abnormalities in spinal and bulbar muscular atrophy
Ranganathan, S., Harmison, G. G., Meyertholen, K., Pennuto, M., Burnett, B. G., & Fischbeck, K. H. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn310 · Cited by 154 · cited 1×
“This mechanism is similar to neural degenerative diseases where induction of ROS (80,113) contributes to motor neuron death (116).”
BackgroundFunctional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells
García‐Prat, L., Sousa‐Victor, P., & Muñoz‐Cánoves, P. (2013) · The FEBS Journal · doi:10.1111/febs.12221 · Cited by 152 · cited 1×
“INTRODUCTION Sarcopenia is associated with increased levels of apoptosis (47) and reduced capabilities for muscle regeneration (41) leading to muscle wasting.”
BackgroundJackson, J. R., Ryan, M. J., & Alway, S. E. (2011) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr047 · Cited by 149 · cited 1×
“Aging increases reactive oxygen species (ROS)–induced production (22) and lowers antioxidant enzyme levels in muscle and neuron cells (58,59,121).”
BackgroundSelf-citationJamart, C., Naslain, D., Gilson, H., & Francaux, M. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00270.2013 · Cited by 148 · cited 1×
“Studies in rodents have shown an increased abundance of autophagy proteins includingDrp1 andBcl-2 and 19 kDa interacting protein-3 (Bnip3) after exercise (60,65,71,78).”
BackgroundTang, H., Inoki, K., Lee, M. C., Wright, E., Khuong, A., Khuong, A., Sugiarto, S., Garner, M. S., Paik, J., DePinho, R. A., et al. (2014) · Science Signaling · doi:10.1126/scisignal.2004809 · Cited by 145 · cited 2×
“Interestingly, inhibition of MTORC1 reduced muscle atrophy via suppression of E3 ligases, Muscle RING Finger 1 (MuRF-1) and MAFbx/atrogin in response to denervation (135).”
BackgroundNuclear apoptosis contributes to sarcopenia
Alway, S. E., & Siu, P. M. (2008) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e318168e9dc · Cited by 144 · cited 1×
“CONCLUSIONS Mitochondrial-regulated apoptosis provides a strong signaling network that contributes to sarcopenia (8).”
BackgroundSelf-citationMahoney, D. J., Rodriguez, C., Devries, M., Yasuda, N., & Tarnopolsky, M. A. (2004) · Muscle & Nerve · doi:10.1002/mus.20004 · Cited by 140 · cited 1×
“For example, increased muscle activity in male G93A SOD1deficient mice contributes to greater motor impairment and motor neuron–accelerated death (82).”
BackgroundMitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle
Porter, C., Hurren, N. M., Cotter, M. V., Bhattarai, N., Reidy, P. T., Dillon, E. L., Durham, W. J., Tuvdendorj, D., Sheffield-Moore, M., Volpi, E., et al. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00125.2015 · Cited by 134
Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and mitophagy
Fedorowicz, M. A., de Vries, R. L. A., Rüb, C., Becker, D., Huang, Y., Zhou, C., Wolken, D. M. A., Voos, W., Liu, Y., & Przedborski, S. (2013) · EMBO Reports · doi:10.1002/embr.201337294 · Cited by 134 · cited 1×
“Pink152 can exit the mitochondria in neuron cells and cleave Parkin, which then suppresses its translocation to the mitochondria to attenuate mitophagy (36).”
BackgroundPGC-1α controls mitochondrial biogenesis and dynamics in lead-induced neurotoxicity
Dabrowska, A. F., Venero, J. L., Iwasawa, R., Hankir, M. K., Rahman, S., Boobis, A. R., & Hajji, N. (2015) · Aging · doi:10.18632/aging.100790 · Cited by 126 · cited 1×
“Our speculation is supported from data that show that in aging-associated neural diseases, there is a loss of mitochondrial function leading to increased mPTP sensitivity, and attenuated mitophagy that contributes to apoptosis (32,68,86,99,111).”
BackgroundJu, J.-S., Jeon, S.-I., Park, J.-Y., Lee, J.-Y., Lee, S.-C., Cho, K.-J., & Jeong, J.-M. (2016) · The Journal of Physiological Sciences · doi:10.1007/s12576-016-0440-9 · Cited by 125 · cited 1×
“Studies in rodents have shown an increased abundance of autophagy proteins includingDrp1 andBcl-2 and 19 kDa interacting protein-3 (Bnip3) after exercise (60,65,71,78).”
BackgroundMitochondrial DNA deletion mutations
McKenzie, D. I., Bua, E. A., McKiernan, S. H., Cao, Z., Wanagat, J., & Aiken, J. M. (2002) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2002.02867.x · Cited by 124 · cited 1×
“Indeed, increased mtDNA mutations have been found in fiber regions that contain oxidative damage (2,90).”
Hao, Y., Jackson, J. R., Wang, Y., Edens, N., Pereira, S. L., & Alway, S. E. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00840.2010 · Cited by 124 · cited 3×
“Nevertheless, future studies should explore themechanisms by which exercise activatesmitophagic, and attenuates apoptotic and necrotic, signaling pathways in muscle cells and motor neurons of older individuals (4,47).”
BackgroundSelf-citationRyan, M. J., Jackson, J. R., Hao, Y., Williamson, C. L., Dabkowski, E. R., Hollander, J. M., & Alway, S. E. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq080 · Cited by 122
Self-citationZhang, Y., Bharathi, S. S., Rardin, M. J., Uppala, R., Verdin, E. M., Gibson, B. W., & Goetzman, E. S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122297 · Cited by 118 · cited 1×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundAlway, S. E., Pereira, S. L., Edens, N. K., Hao, Y., & Bennett, B. T. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.06.005 · Cited by 114 · cited 2×
“In the quest to attenuate sarcopenia, it also will be important to understand the limit for mitochondrial health to impact satellite cell function for repairing and replacing sections of fibers or whole fibers because satellite cells are affected adversely by aging, mitochondrial damage, and death signaling (4,6,7,144…”
BackgroundSelf-citationMarzetti, E., Carter, C. S., Wohlgemuth, S. E., Lees, H. A., Giovannini, S., Anderson, B., Quinn, L. S., & Leeuwenburgh, C. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.12.008 · Cited by 113 · cited 1×
“Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents (4,7,26,34,47,77,88,130) and humans (44,145).”
BackgroundAutophagy and amyotrophic lateral sclerosis: The multiple roles of lithium
Fornai, F., Longone, P., Ferrucci, M., Lenzi, P., Isidoro, C., Ruggieri, S., & Paparelli, A. (2008) · Autophagy · doi:10.4161/auto.5923 · Cited by 111 · cited 2×
“Defective mitophagy underlies the progression of motor neuron death in amyotrophic lateral sclerosis (ALS) (38).”
BackgroundA robust neuromuscular system protects rat and human skeletal muscle from sarcopenia
Pannérec, A., Springer, M., Migliavacca, E., Ireland, A., Piasecki, M., Karaz, S., Jacot, G., Métairon, S., Danenberg, E., Raymond, F., et al. (2016) · Aging · doi:10.18632/aging.100926 · Cited by 110
Sirt1 protects the heart from aging and stress
Hsu, C., Odewale, I., Alcendor, R. R., & Sadoshima, J. (2008) · Biological Chemistry · doi:10.1515/bc.2008.032 · Cited by 108 · cited 1×
“Activated SIRT1 deacetylates and activates PCG-1α, which promotes mitochondria synthesis, assembly, growth, and mitochondrial antioxidant production (54).”
BackgroundAutophagic response to exercise training in skeletal muscle with age
Kim, Y. A., Kim, Y. S., Oh, S. L., Kim, H.-J., & Song, W. (2013) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-013-0246-7 · Cited by 108 · cited 2×
“However, mitophagy is attenuated with aging in skeletal muscle and motor neurons (40,63,70,127).”
BackgroundBori, Z., Zhao, Z., Koltai, E., Fatouros, I. G., Jamurtas, A. Z., Douroudos, I. I., Terzis, G., Chatzinikolaou, A., Sovatzidis, A., Draganidis, D., et al. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.03.004 · Cited by 108 · cited 1×
“However, to provide a balanced perspective, it is important to point out that other studies have found higher fusion profiles in muscles of humans (14) and prematurely aged mice (63) and larger mitochondria in muscles of old mice (75).”
ResultCheema, N., Herbst, A., McKenzie, D., & Aiken, J. M. (2015) · Aging Cell · doi:10.1111/acel.12399 · Cited by 107 · cited 6×
“We have focused on ROS damage to the inner mitochondrial membrane (15,21,22,79) and mtDNA damage (22,26,50,63,73) as two important ways that might impair mitochondrial function in aging muscles and motor neurons.”
BackgroundInfluentialParkinson-susceptibility gene DJ-1/PARK7 protects the murine heart from oxidative damage in vivo
Billia, F., Hauck, L., Grothe, D., Konecny, F. A., Rao, V., Kim, R. H., & Mak, T. W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303444110 · Cited by 107 · cited 1×
“PARK7 is an antioxidant protein that limits mitochondrial damage in response to oxidative stress (12), and it regulates skeletal muscle contractile protein synthesis and hypertrophy (149).”
BackgroundMittal, K., & Logmani, F. H. (1987) · Journal of Gerontology · doi:10.1093/geronj/42.1.8 · Cited by 107 · cited 1×
“However, sarcopenia in aged humans and rodents also is associated with motor neuronal death (96,139), which causes impaired innervation (48,106), and a ~27% reduction in the motor unit pool.”
BackgroundWang, B., Cai, Z., Tao, K., Zeng, W., Lu, F., Yang, R., Feng, D., Gao, G., & Yang, Q. (2016) · Autophagy · doi:10.1080/15548627.2016.1179401 · Cited by 107
Jackson, J. R., Ryan, M. J., Hao, Y., & Alway, S. E. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00489.2010 · Cited by 105 · cited 1×
“Aging increases reactive oxygen species (ROS)–induced production (22) and lowers antioxidant enzyme levels in muscle and neuron cells (58,59,121).”
BackgroundSelf-citationO′Leary, M. F. N., Vainshtein, A., Carter, H. N., Zhang, Y., & Hood, D. A. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00451.2011 · Cited by 105 · cited 1×
“High levels of apoptotic signaling (1,129) and altered autophagy signaling (102,103) with elevated UPS activity (137) occur in muscles after spinal cord injury or denervation.”
BackgroundMartin, L. J., & Liu, Z.-P. (2002) · Journal of Neurobiology · doi:10.1002/neu.10026 · Cited by 104 · cited 1×
“In neurons, DNA damage precedes neuronal apoptosis (85), whereas forced repair of DNA damage rescues neurons from elimination by apoptosis (86).”
BackgroundMFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons
Wang, W., Zhang, F., Li, L., Tang, F., Siedlak, S. L., Fujioka, H., Liu, Y., Su, B., Pi, Y., & Wang, X. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.617167 · Cited by 103 · cited 1×
“Furthermore, increased mitochondrial fragmentation has been found to precede glutamate-induced death of motor neurons (143).”
BackgroundDenervation drives mitochondrial dysfunction in skeletal muscle of octogenarians
Spendiff, S., Vuda, M., Gouspillou, G., Aare, S., Pérez, A., Morais, J. A., Jagoe, R. T., Filion, M., Glicksman, R., Kapchinsky, S., et al. (2016) · The Journal of Physiology · doi:10.1113/jp272487 · Cited by 101 · cited 3×
“Mitochondrial stress in aging can originate from greater levels of oxidants, DNA damage, or denervation (31,133).”
BackgroundVimentin/cardiolipin complex as a new antigenic target of the antiphospholipid syndrome
Ortona, E., Capozzi, A., Colasanti, T., Conti, F., Alessandri, C., Longo, A., Garofalo, T., Margutti, P., Misasi, R., Khamashta, M. A., et al. (2010) · Blood · doi:10.1182/blood-2010-04-279208 · Cited by 99 · cited 1×
“Furthermore, interaction of cardiolipin with the structural protein vimentin (104) could provide a localized cell signaling site for targeted apoptotic disassembly and removal via antivimentin/CL complex antibodies, as has been observed in several pathologies involving apoptosis (104).”
BackgroundRojas, F., González, D., Cortés, N., Ampuero, E., Hernández, D. E., Fritz, E., Abarzúa, S., Martinez, A. N., Elorza, Á. A., Alvarez, A. R., et al. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00203 · Cited by 97 · cited 1×
“This mechanism is similar to neural degenerative diseases where induction of ROS (80,113) contributes to motor neuron death (116).”
BackgroundDenervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats
Alway, S. E., Degens, H., Krishnamurthy, G., & Chaudhrai, A. (2003) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/58.8.b687 · Cited by 96 · cited 1×
“In aging, a loss of innervation induces profound muscle atrophy (5,106,129).”
BackgroundSelf-citationAmigo, I., Menezes‐Filho, S. L., Luévano‐Martínez, L. A., Chausse, B., & Kowaltowski, A. J. (2017) · Aging Cell · doi:10.1111/acel.12527 · Cited by 95 · cited 2×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundThe Impact of Pathogenic Mitochondrial DNA Mutations on Substantia Nigra Neurons
Reeve, A. K., Meagher, M., Lax, N., Simcox, E. M., Hepplewhite, P. D., Jaros, E., & Turnbull, D. M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3525-12.2013 · Cited by 94 · cited 1×
“Furthermore, aging-induced mtDNA deletions are associated closely with a loss of mitochondrial function in motor neurons (123), neuronal malfunction in diseases like Parkinson disease (115), and muscle loss with aging (50,91).”
BackgroundRyan, M. J., Jackson, J. R., Hao, Y., Leonard, S. S., & Alway, S. E. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.002 · Cited by 94 · cited 1×
“Aging increases reactive oxygen species (ROS)–induced production (22) and lowers antioxidant enzyme levels in muscle and neuron cells (58,59,121).”
BackgroundSelf-citationMitochondrial DNA deletion mutations and sarcopenia
AIKEN, J., BUA, E., CAO, Z., LOPEZ, M., WANAGAT, J., McKENZIE, D., & McKIERNAN, S. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02111.x · Cited by 85 · cited 1×
“Indeed, increased mtDNA mutations have been found in fiber regions that contain oxidative damage (2,90).”
BackgroundMohamed, J. S., Wilson, J. C., Myers, M. J., Sisson, K. J., & Alway, S. E. (2014) · Aging · doi:10.18632/aging.100696 · Cited by 83 · cited 2×
“Proteins like SIRT1 and SIRT3 may be important regulators of deacetylation in mitochondria (46,97,132).”
BackgroundSelf-citationPgc-1α overexpression Via local transfection attenuates mitophagy pathway in muscle disuse atrophy
Kang, C., & Ji, L. L. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.12.032 · Cited by 83 · cited 2×
“However, overexpression of PGC-1α was reported to attenuate Pink1 levels in response to remobilization of muscle (67).”
BackgroundPrecht, T. A., Phelps, R. A., Linseman, D. A., Butts, B. D., Le, S. S., Laessig, T. A., Bouchard, R. J., & Heidenreich, K. A. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401552 · Cited by 81 · cited 1×
“Our speculation is supported from data that show that in aging-associated neural diseases, there is a loss of mitochondrial function leading to increased mPTP sensitivity, and attenuated mitophagy that contributes to apoptosis (32,68,86,99,111).”
BackgroundYonashiro, R., Kimijima, Y., Shimura, T., Kawaguchi, K., Fukuda, T., Inatome, R., & Yanagi, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114985109 · Cited by 78 · cited 1×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundMartínez-Redondo, V., Jannig, P. R., Correia, J. C., Ferreira, D. M. S., Červenka, I., Lindvall, J. M., Sinha, I., Izadi, M., Pettersson-Klein, A. T., Agudelo, L. Z., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.705822 · Cited by 74 · cited 1×
“PGC-1α2, PGC-1α3, and PGC-1α4 have been shown to stimulate protein synthesis and attenuate UPS activity in cultured myotubes and mouse skeletal muscle (87,119).”
BackgroundAlway, S. E., Bennett, B. T., Wilson, J. C., Sperringer, J., Mohamed, J. S., Edens, N. K., & Pereira, S. L. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00674.2014 · Cited by 73 · cited 4×
“Nevertheless, future studies should explore themechanisms by which exercise activatesmitophagic, and attenuates apoptotic and necrotic, signaling pathways in muscle cells and motor neurons of older individuals (4,47).”
BackgroundInfluentialSelf-citationPost-translational modification of mitochondria as a novel mode of regulation
Hofer, A., & Wenz, T. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.006 · Cited by 70 · cited 1×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundCilenti, L., Ambivero, C. T., Ward, N., Alnemri, E. S., Germain, D., & Zervos, A. S. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.03.027 · Cited by 70 · cited 1×
“For example, a reduced inhibition of the E3 ligase Omi/ HtrA2 in neuronal mitochondria contributes to a decrease in Mfn2 leading to attenuated mitophagy (29).”
BackgroundEffects of aerobic training on markers of autophagy in the elderly
Mejías-Peña, Y., Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Martínez-Flórez, S., Almar, M., de Paz, J. A., Cuevas, M. J., & González-Gallego, J. (2016) · AGE · doi:10.1007/s11357-016-9897-y · Cited by 69 · cited 1×
“(92), who found an increase in the protein abundance of autophagy proteins Beclin-1, Atg12, Atg16, and the LC3II/I ratio in blood mononuclear cells of elderly subjects after 8 wk of aerobic exercise.”
BackgroundThe Involvement of Lysosomes in Myocardial Aging and Disease
Terman, A., Kurz, T., Gustafsson, B., & BRUNK, U. T. (2008) · Current Cardiology Reviews · doi:10.2174/157340308784245801 · Cited by 68 · cited 1×
“Further work is needed to determine if lysosomal dysfunction (136), loss of Mfn2, or some other protein involved in mitochondrial dynamics regulates mitophagy in sarcopenia.”
BackgroundNeuron specific reduction in cuznsod is not sufficient to initiate a full sarcopenia phenotype
Sataranatarajan, K., Qaisar, R., Davis, C., Sakellariou, G. K., Vasilaki, A., Zhang, Y., Liu, Y., Bhaskaran, S., McArdle, A., Jackson, M., et al. (2015) · Redox Biology · doi:10.1016/j.redox.2015.04.005 · Cited by 67 · cited 2×
“The importance of antioxidants in sarcopenia is highlighted by observations that both neural and muscle losses of the cytosolic antioxidant CuZn-superoxide dismutase (CuZnSOD) recapitulated sarcopenic muscle loss in a mouse model (125).”
BackgroundMitochondrial dynamic abnormalities in amyotrophic lateral sclerosis
Jiang, Z., Wang, W., Perry, G., Zhu, X., & Wang, X. (2015) · Translational Neurodegeneration · doi:10.1186/s40035-015-0037-x · Cited by 66 · cited 1×
“However, dysfunction of mitochondrial dynamics has been reported as an early event in amyotrophic lateral sclerosis (61), which is a common motor neuron disease.”
BackgroundHou, Y., Ghosh, P., Wan, R., Ouyang, X., Cheng, H., Mattson, M. P., & Cheng, A. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.11.002 · Cited by 66 · cited 1×
“Similar to skeletal muscle cells, ROS damage to mitochondria in neurons from aged animals contributes to mPTP opening (53).”
BackgroundLatent mitochondrial DNA deletion mutations drive muscle fiber loss at old age
Herbst, A. J., Wanagat, J., Cheema, N., Widjaja, K., McKenzie, D. I., & Aiken, J. M. (2016) · Aging Cell · doi:10.1111/acel.12520 · Cited by 66 · cited 2×
“Furthermore, aging-induced mtDNA deletions are associated closely with a loss of mitochondrial function in motor neurons (123), neuronal malfunction in diseases like Parkinson disease (115), and muscle loss with aging (50,91).”
BackgroundUbiquitin expression is up-regulated in human and rat skeletal muscles during aging
Cai, D., Lee, K. K. H., Li, M., Tang, M. K., & Chan, K. M. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.02.027 · Cited by 65 · cited 2×
“For example, ubiquitin (17), 26S proteasome, polyubiquitinated proteins (3), MuRF-1, and MAFbx expression were all reported to be elevated in hindlimb muscles of sarcopenic rats as compared with young adult animals (3,30).”
BackgroundInorganic mercury is transported from muscular nerve terminals to spinal and brainstem motoneurons
Arvidson, B. (1992) · Muscle & Nerve · doi:10.1002/mus.880151006 · Cited by 62 · cited 1×
“This has been known for several decades because, when toxins or other compounds are injected into muscles, the compounds undergo retrograde transport to the neuromuscular junction (105), deposit in motor neurons (11), and sometimes contribute to motor neuronal dysfunction (reviewed in (33,39).”
BackgroundDeficiency of the Bax gene attenuates denervation-induced apoptosis
Siu, P. M., & Alway, S. E. (2006) · APOPTOSIS · doi:10.1007/s10495-006-6315-4 · Cited by 61 · cited 1×
“This communication also is seen when spinal cord injury or denervation induces large-scalemuscle wasting (57,76,107,129,131,137), and denervation is a condition often seen as part of sarcopenia.”
BackgroundSelf-citationRyan, M. J., Dudash, H. J., Docherty, M., Geronilla, K. B., Baker, B. A., Haff, G. G., Cutlip, R. G., & Alway, S. E. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.10.1015 · Cited by 60
Self-citationTriplett, J. C., Zhang, Z., Sultana, R., Cai, J., Klein, J. B., Büeler, H., & Butterfield, D. A. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13039 · Cited by 58 · cited 2×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundWhy are many mRNAs translated to the vicinity of mitochondria: A role in protein complex assembly?
Margeot, A., Garcia, M., Wang, W., Tetaud, E., di Rago, J. P., & Jacq, C. (2005) · Gene · doi:10.1016/j.gene.2005.04.022 · Cited by 57
MTORC1 determines autophagy through ULK1 regulation in skeletal muscle
Castets, P., & Rüegg, M. A. (2013) · Autophagy · doi:10.4161/auto.25722 · Cited by 57 · cited 17×
“FOXOs activate lysosomal cathepsins and cytosolic protease calpains, which progress toward ATP-dependent UPS activation via FOXO3aassociated MuRF-1 and MAFbx regulation (reviewed in (66,117)).”
BackgroundInfluentialJoseph, A.-M., Malamo, A. G., Silvestre, J. G. O., Wawrzyniak, N., Carey‐Love, S., Nguyen, L. M. ‐., Dutta, D., Xu, J., Leeuwenburgh, C., & Adhihetty, P. J. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.05.061 · Cited by 56 · cited 1×
“If the same processes occur in humans as is the case in rodents and nonhuman mammals (64), exercise, or nutritional intervention such as caloric restriction, also would be expected to increase mitophagy removal of dysfunctional mitochondria, so the mitochondria that remain are proportionally healthier (64).”
BackgroundSarcopenic Obesity in Adults With Spinal Cord Injury: A Cross-Sectional Study
Pelletier, C., Miyatani, M., Giangregorio, L., & Craven, B. C. (2016) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2016.04.026 · Cited by 55 · cited 1×
“This communication also is seen when spinal cord injury or denervation induces large-scalemuscle wasting (57,76,107,129,131,137), and denervation is a condition often seen as part of sarcopenia.”
BackgroundKitaoka, Y., Ogasawara, R., Tamura, Y., Fujita, S., & Hatta, H. (2015) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2015-0184 · Cited by 54 · cited 1×
“Studies in rodents have shown an increased abundance of autophagy proteins includingDrp1 andBcl-2 and 19 kDa interacting protein-3 (Bnip3) after exercise (60,65,71,78).”
BackgroundMitochondria, motor neurons and aging
García, M. L., Fernández, A., & Solas, M. T. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.03.019 · Cited by 54
Transient systemic mtDNA damage leads to muscle wasting by reducing the satellite cell pool
Wang, X., Pickrell, A. M., Rossi, S. G., Pinto, M., Dillon, L. M., Hida, A., Rotundo, R. L., & Moraes, C. T. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt251 · Cited by 54 · cited 2×
“MITOCHONDRIAL PERMEABILITY TRANSITION PORE SENSITIZATION WITH AGING — MITOCHONDRIAL DYSFUNCTION Stress-induced damage to mitochondrial membranes (40,108,144,147) contributes to sensitization of the mitochondrial permeability transition pore (44).”
BackgroundA novel role for the mitochondrial HTRA2/OMI protease in aging
Kang, S., Fernandes‐Alnemri, T., & Alnemri, E. S. (2012) · Autophagy · doi:10.4161/auto.22920 · Cited by 51 · cited 1×
“Our speculation is supported from data that show that in aging-associated neural diseases, there is a loss of mitochondrial function leading to increased mPTP sensitivity, and attenuated mitophagy that contributes to apoptosis (32,68,86,99,111).”
BackgroundThe role of mitochondrial fusion and fission in skeletal muscle function and dysfunction
Hood, D. A. (2015) · Frontiers in Bioscience · doi:10.2741/4303 · Cited by 50 · cited 1×
“Indeed, this seems to be the case because electronmicroscopy and biochemical analyses have shown small, more fragmented mitochondria in muscles from old as compared with young adult hosts (56,57), although very large mitochondria also have been noted in muscles from old animals (75).”
ResultMohan, R., Tosolini, A. P., & Morris, R. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.045 · Cited by 48 · cited 1×
“Furthermore, the presynaptic motor endplate of the neuromuscular junction is critical for providing retrograde transport to themotor neuron (98).”
BackgroundThe P66Shc/mitochondrial permeability transition pore pathway determines neurodegeneration
Savino, C., Pelicci, P., & Giorgio, M. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/719407 · Cited by 46 · cited 1×
“This occurs through p66Shc, which generates H2O2 that in turn reacts with cytochrome c and induces oxidation of the mPTP and mitochondrial swelling (126).”
BackgroundMotor unit number estimation and neuromuscular fidelity in 3 stages of sarcopenia
Gilmore, K. J., Morat, T., Doherty, T. J., & Rice, C. L. (2016) · Muscle & Nerve · doi:10.1002/mus.25394 · Cited by 44 · cited 1×
“Some denervated fibers become innervated by axons from surviving motor neurons (42,45), whereas other fibers remain denervated and contribute to functional losses in sarcopenia (42).”
BackgroundNatale, G., Lenzi, P., Lazzeri, G., Falleni, A., Biagioni, F., Ryskalin, L., & Fornai, F. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00434 · Cited by 42 · cited 1×
“In contrast, lithium-induced induction of mitophagy (38,101) and mitochondrial biogenesis (101) improve mitochondrial morphology in motor neurons of a G93A SOD-1 mouse model of ALS.”
BackgroundQuantification of Ceroid and Lipofuscin in Skeletal Muscle
Tohma, H., Hepworth, A. R., Shavlakadze, T., Grounds, M. D., & Arthur, P. G. (2011) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155411412185 · Cited by 42 · cited 1×
“Indeed, lipofuscin deposits have been reported previously in many tissues including muscles and neurons of aged rodents or other mammals (138).”
BackgroundSpecific protein changes contribute to the differential muscle mass loss during ageing
Capitanio, D., Vasso, M., Palma, S. D., Fania, C., Torretta, E., Cammarata, F. P., Magnaghi, V., Procacci, P., & Gelfi, C. (2015) · PROTEOMICS · doi:10.1002/pmic.201500395 · Cited by 42 · cited 2×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundRespiratory chain deficiency in aged spinal motor neurons
Rygiel, K. A., Grady, J. P., & Turnbull, D. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.02.027 · Cited by 41 · cited 2×
“Furthermore, aging-induced mtDNA deletions are associated closely with a loss of mitochondrial function in motor neurons (123), neuronal malfunction in diseases like Parkinson disease (115), and muscle loss with aging (50,91).”
BackgroundLongitudinal analysis of early stage sarcopenia in aging rhesus monkeys
McKiernan, S. H., Colman, R. J., Lopez, M. E., Beasley, T. M., Weindruch, R. H., & Aiken, J. M. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.09.014 · Cited by 38 · cited 2×
“Whereas elevated ROS production is not solely the result of mtDNA deletions or mtDNA mutations (141), it is clear that this mechanism contributes to mitochondrial ROS production in aging muscles and neurons (26,86,91).”
BackgroundSin, T. K., Yu, A. P., Yung, B. Y., Yip, S. P., Chan, L., Wong, S. C. C., Rudd, J. A., & Siu, P. M. (2015) · Acta Diabetologica · doi:10.1007/s00592-015-0767-3 · Cited by 32 · cited 1×
“We know that exercise downregulates apoptosis and upregulates mitophagy (4,52,128,146).”
BackgroundManganelli, V., Capozzi, A., Recalchi, S., Signore, M., Mattei, V., Garofalo, T., Misasi, R., Esposti, M. D., & Sorice, M. (2015) · Journal of Immunology Research · doi:10.1155/2015/847985 · Cited by 31 · cited 1×
“Cardiolipin is an important mitochondria-specific phospholipid, which is concentrated between inner and outer mitochondrial membranes, and redistribution of cardiolipin leads to a localized oligomerization of proapoptotic proteins (83).”
BackgroundEndocytosis and retrograde axonal traffic in motor neurons.
Deinhardt, K., & Schiavo, G. (2005) · Biochemical Society Symposia · doi:10.1042/bss0720139 · Cited by 30 · cited 1×
“This has been known for several decades because, when toxins or other compounds are injected into muscles, the compounds undergo retrograde transport to the neuromuscular junction (105), deposit in motor neurons (11), and sometimes contribute to motor neuronal dysfunction (reviewed in (33,39).”
BackgroundLiu, X., Xu, S., Wang, P., & Wang, W. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.05.010 · Cited by 28 · cited 1×
“This mechanism is similar to neural degenerative diseases where induction of ROS (80,113) contributes to motor neuron death (116).”
BackgroundMotoneuron and muscle fiber succinate dehydrogenase activity in control and overloaded plantaris
Chalmers, G. R., Roy, R. R., & Edgerton, V. R. (1991) · Journal of Applied Physiology · doi:10.1152/jappl.1991.71.4.1589 · Cited by 28 · cited 1×
“Further evidence of a muscle-to-motor neuron feedback pathway is supported from data showing increases in mitochondrial succinate dehydrogenase activity in motor neurons after functional overload of the plantaris hindlimbmuscle in cats (25).”
BackgroundApoptosis in young and old denervated rat skeletal muscle
Lee, G., Lim, J., & Frontera, W. R. (2016) · Muscle & Nerve · doi:10.1002/mus.25221 · Cited by 27
Martin, L. J., & Wong, M. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.06.011 · Cited by 25 · cited 3×
“In neurons, DNA damage precedes neuronal apoptosis (85), whereas forced repair of DNA damage rescues neurons from elimination by apoptosis (86).”
BackgroundAging alters the reduction of pro-apoptotic signaling in response to loading-induced hypertrophy
Siu, P. M., & Alway, S. E. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2005.11.004 · Cited by 24
Self-citationWanagat, J., Ahmadieh, N., Bielas, J. H., Ericson, N. G., & Remmen, H. V. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.11.012 · Cited by 22 · cited 1×
“Whereas elevated ROS production is not solely the result of mtDNA deletions or mtDNA mutations (141), it is clear that this mechanism contributes to mitochondrial ROS production in aging muscles and neurons (26,86,91).”
BackgroundDeacetylation of mitofusin-2 by sirtuin-1: A critical event in cell survival after ischemia
Sooyeon, L., Go, K. L., & Kim, J. (2015) · Molecular & Cellular Oncology · doi:10.1080/23723556.2015.1087452 · Cited by 21 · cited 2×
“Proteins like SIRT1 and SIRT3 may be important regulators of deacetylation in mitochondria (46,97,132).”
BackgroundMoussa, C. E.-H. (2015) · Neurodegenerative Diseases · doi:10.1159/000430888 · Cited by 13 · cited 3×
“However, mitochondrial damage and modifications also may occur by posttranslational modifications such as ubiquitination (67,99,140,148), acetylation (9,21,28), succinylation (114,150), and phosphorylation (51,73,79).”
BackgroundPark7 Expression Influences Myotube Size and Myosin Expression in Muscle
Yu, H. M., Waddell, J. N., Kuang, S., & Bidwell, C. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092030 · Cited by 13 · cited 1×
“PARK7 is an antioxidant protein that limits mitochondrial damage in response to oxidative stress (12), and it regulates skeletal muscle contractile protein synthesis and hypertrophy (149).”
BackgroundMolecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury
Thakore, N. P., Samantaray, S., Park, S., Nozaki, K., Smith, J. A., Cox, A., Krause, J. S., & Banik, N. L. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1696-9 · Cited by 11 · cited 2×
“High levels of apoptotic signaling (1,129) and altered autophagy signaling (102,103) with elevated UPS activity (137) occur in muscles after spinal cord injury or denervation.”
BackgroundPamphlett, R., & Bayliss, A. (1992) · Muscle & Nerve · doi:10.1002/mus.880150514 · Cited by 9
Denervation, Reinnervation and Regeneration of Senile Muscle
GUTMANN, E., & Hanzlíková, V. (1975) · Advances in experimental medicine and biology · doi:10.1007/978-1-4757-0731-1_36 · Cited by 5 · cited 1×
“Some denervated fibers become innervated by axons from surviving motor neurons (42,45), whereas other fibers remain denervated and contribute to functional losses in sarcopenia (42).”
Background
Research works printed but not linked: 1
- 2009, Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle, Appl. Physiol. Nutr. Metab, 34, 465
Cited by
Sorted by citations
Sarcopenia, frailty and their prevention by exercise
Nascimento, C. M., Ingles, M., Salvador-Pascual, A., Cominetti, M. R., Gomez-Cabrera, M. C., & Viña, J. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.035 · Cited by 396
Mitochondrial dysfunction: roles in skeletal muscle atrophy
Chen, X., Ji, Y., Liu, R., Zhu, X., Wang, K., Yang, X., Liu, B., Gao, Z., Huang, Y. H., Shen, Y., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04369-z · Cited by 362
Post-COVID-19 acute sarcopenia: physiopathology and management
Piotrowicz, K., Gąsowski, J., Michel, J., & Veronese, N. (2021) · Aging Clinical and Experimental Research · doi:10.1007/s40520-021-01942-8 · Cited by 257
The Role of Oxidative Stress in Skeletal Muscle Myogenesis and Muscle Disease
Lian, D., Chen, M.-M., Wu, H., Deng, S., & Hu, X. (2022) · Antioxidants · doi:10.3390/antiox11040755 · Cited by 232
“Moreover mitochondrial regulation of muscle metabolism and mitochondrial dysfunction may play a role in sarcopenia [93].”
BackgroundMolecular Mechanisms of Inflammation in Sarcopenia: Diagnosis and Therapeutic Update
Jiménez-Gutiérrez, G. E., Martínez-Gómez, L. E., Martínez-Armenta, C., Pineda, C., Martínez‐Nava, G. A., & López-Reyes, A. G. (2022) · Cells · doi:10.3390/cells11152359 · Cited by 245
“These mitochondrial changes are major factors that contribute to the age-dependent muscle degeneration observed in sarcopenia [96].”
Background
Metadata
- Authors
- Alway, S. E., Mohamed, J. S., & Myers, M. J.
- Affiliations
- West Virginia University (US)
- Corresponding author
- Alway, Stephen E.
- Venue
- Exercise and Sport Sciences Reviews
- Published
- 2017-04
- Volume
- 45
- Issue
- 2
- Pages
- 58-69
- ISSN
- 0091-6331 (ISSN-L)
- 1538-3008
- PMC
- PMC5357179
- OpenAlex
- W2576104985
- Semantic Scholar
- a327c586451d76c3458f3b2dcee83eaa79f8426b
- Cited by
- 153
- References
- 151
- Citations by year
- 2026: 10 · 2025: 24 · 2024: 24 · 2023: 22 · 2022: 17 · 2021: 17 · 2020: 16 · 2019: 13 · 2018: 8 · 2017: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Exercise and Sport Sciences Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Research Repository @ WVU (West Virginia University) (submittedVersion)
- Funders
- West Virginia University
- National Institutes of Health (2p20rr016477-09, 1p30rr032138-01)
- National Institute of General Medical Sciences (P30GM103488, P20GM103434, U54GM104942)
- National Center for Research Resources (P30-RR-032138, P20-RR016477, P20RR016440)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- sarcopenia, mitochondrial dysfunction, motor neuron degeneration, signaling pathways, sarcopenia prevention
- MeSH terms
- Forkhead Box Protein O1, Aging, Animals, Humans, Mitochondria, Muscle, Motor Neurons, Muscular Atrophy, Signal Transduction, Cell Death, Apoptosis, Muscle, Skeletal, Ubiquitin, Sarcopenia, Mitophagy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
