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Telomere dysfunction induces metabolic and mitochondrial compromise
Open accessAbstract
Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1α and PGC-1β, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1α expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.
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TL;DR
Telomere dysfunction in mice represses PGC-1α and PGC-1β through p53, impairing mitochondrial function and metabolism. This telomere–p53–PGC pathway links telomere attrition to cardiomyopathy, defective gluconeogenesis, and stem cell decline.
Key findings
- Transcriptomic profiling of haematopoietic stem cells, heart, and liver from G4 Tert−/− mice showed broad repression of the PGC-1α/β network, including oxidative phosphorylation, oxidative defence, gluconeogenesis, fatty acid/cholesterol synthesis, and β-oxidation genes; RT–qPCR and western blot confirmed lower PGC-1α/β and targets such as NRF-1, ERRα, PPARα, and TFAM.
- Mitochondrial consequences included reduced mitochondrial DNA content and density, lower complex I and IV activity, decreased state III respiration, reduced uncoupled respiration in G4 liver and heart (31% and 25%, respectively), lower ATP synthesis/content, and increased ROS/H2O2 production.
- G4 mice developed dilated cardiomyopathy by 15 months, showed a 30% drop in plasma glucose after 12 h fasting, and had impaired HSC reconstitution; adenoviral Tert partially restored PGC targets and raised glucose by 30% in vivo and 80% in cultured G4 hepatocytes, while adenoviral PGC-1α increased state III and IV respiration in G4 liver mitochondria by 3.1-fold and 3.2-fold.
- p53 deficiency restored PGC expression and mitochondrial DNA copy number; p53–ER activation repressed PGCs and reduced mitochondrial mass by 10–15%; p53 bound PGC-1α/β promoters and repressed reporters fivefold; p53 loss improved fractional shortening by 30% in a doxorubicin cardiomyopathy protocol.
Methods
- Used Tert−/− mice across WT, G1, and G4 generations, Terc−/− G2 mice, and p53−/− backgrounds; profiled HSCs, liver, and heart by microarray with SAM or fold-change analysis and Ingenuity pathway analysis, followed by RT–qPCR and western blot.
- Assessed mitochondrial and metabolic phenotypes via qPCR-based mtDNA quantification, HPLC ATP measurement, Seahorse XF24 and Clark electrode respiration, ROS and carbonylated protein assays, fasting glucose, hepatocyte gluconeogenesis, echocardiography, and competitive transplantation.
- Mechanistic tests included adenoviral Tert or PGC-1α delivery, p53–ER MEF activation, PGC promoter luciferase reporters, anti-p53 chromatin immunoprecipitation, and doxorubicin-induced cardiomyopathy.
Limitations
- No dedicated limitations section is present; the authors state that the relative contributions of DNA damage checkpoints versus metabolic/mitochondrial dysfunction require further study, and that p53-mediated PGC repression is context-dependent.
- Evidence comes from mouse genetic models and cell systems, with no human data; germline p53 deletion and adenoviral overexpression may introduce pleiotropic or context-specific effects.
- The ROS scavenger N-acetylcysteine did not rescue defective HSC repopulation, indicating increased ROS is not central to HSC failure, although its role in other phenotypes is not fully resolved.
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46 Own result · 12 Own interpretation · 11 Not checked yet · 2 Own method
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“This impaired mitochondrial ATP synthesis is associated with decreased total ATP content in G4 hearts and livers (Fig. 2d).”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“This Ad-PGC-1α impact was markedly more pronounced in G4 mice than in WT mice or hepatocytes.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
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“cultured G4 hepatocytes which show an 80% increase in glucose output relative to Ad-GFP controls”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
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“respiration uncoupled from ATP synthesis (induced by 2,4-dinitrophenol, DNP) was also reduced in G4 liver and heart mitochondria (31% and 25%, respectively)”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“Functionally, telomere dysfunction correlated with a marked decline in complex I and IV activity when assayed with either whole tissue lysates or isolated mitochondria from G1 and G4 heart and liver tissues”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“G4 mice also showed decreased blood triglyceride and cholesterol levels”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction represses PGC network and mitochondrial biogenesis
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“Additionally, complex II- and complex IV-dependent respiration was also decreased in G4 mitochondria”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“Telomere dysfunction transcriptomes showed strong enrichment for networks regulated by PGC-1α and PGC-1β including oxidative phosphorylation (OXPHOS), mitochondrial function, oxidative stress and gluconeogenesis”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction represses PGC network and mitochondrial biogenesis
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“while running endurance capacity was significantly reduced in G4 mice”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction represses PGC network and mitochondrial biogenesis
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“Ad-Tert had no effect on gluconeogenesis in WT mice”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
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“G4 mice also exhibited an inability to maintain plasma glucose levels under fasting conditions, experiencing a marked 30% drop at 12 h of fasting, yet maintained normal plasma glucose levels under fed conditions”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
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“In this model, progressive telomere shortening is associated with increasing atrophy and functional decline across proliferative organs (intestinal, haematopoietic) and equally profound impairment in relatively quiescent organs (liver and heart) that do not exhibit significant levels of apoptosis”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction represses PGC network and mitochondrial biogenesis
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“as well as reductions in PGC and targets, mitochondrial DNA content, complex I and IV activity, and ATP levels”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“Body composition analysis showed body weight reduction and striking decrease in fat mass with preserved lean mass, yet no differences in spontaneous activity or food intake were apparent”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction represses PGC network and mitochondrial biogenesis
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“this PGC-mitochondrial link is supported by Ad-PGC-1α-induced rescue of gluconeogenesis in vivo and in vitro in G4 hepatocytes”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
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“G4 Tert−/− mice exhibited these classical signs of impaired PGC function, including an age-progressive dilated cardiomyopathy with left ventricular wall thinning, increased left ventricular diameter, and reduced fractional shortening by 15 months of age”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
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“We documented reduced mitochondrial DNA content (Fig. 2a) and reduced mitochondrial density in G1 and G4 heart and liver”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“which aligned with increased ROS levels by FACS in HSCs and increased carbonylated proteins in liver homogenates”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“WT MEF or heart tissues of mice treated with the DNA damage agent doxorubicin showed increased p53 levels after 24 h and coincident binding of p53 to PGC-1α promoter and repression of PGC-1α levels”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > p53 directly represses PGC-1α and PGC-1β
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“anti-p53 chromatin-immunoprecipitation assays in G2 Terc−/− p53+/+, but not G2 Terc−/− p53−/−, MEFs demonstrated physical binding between p53 and (1) PGC-1α fragments containing p53 binding elements at −564 and −954, but not −2317, and (2) PGC1β fragments containing p53 binding elements at −1616 and −1030”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > p53 directly represses PGC-1α and PGC-1β
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“after 48 h of OHT treatment, G2 Terc−/− p53−/− p53–ER MEFs showed a 10–15% decrease in mitochondrial mass compared with no significant change in the OHT-treated G2 Terc−/− p53−/− controls”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > p53 directly represses PGC-1α and PGC-1β
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“Increasing dosage of p53 in either p53−/− or G2 p53−/− MEFs showed repressed PGC-1α and PGC-1β levels and increasing occupancy of p53 binding elements in PGC-1α and PGC-1β promoters”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > p53 directly represses PGC-1α and PGC-1β
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“Taken together, these collective data establish that telomere-dysfunction-induced repression of the PGC network is associated with mitochondrial dysfunction as evidenced by compromised OXPHOS and respiration, decreased ATP generation capacity, and increased oxidative stress.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction decreases mitochondrial mass and energy production
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“In summary, multiple levels of evidence establish telomere dysfunction-induced p53 represses PGC-1α and PGC-1β, thereby linking telomeres to mitochondrial biology, oxidative defence, and metabolism.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Discussion
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In the paper
“We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Abstract
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In the paper
“In the absence of telomerase, continued cell division results in telomere shortening, loss of ‘capping’ function, and p53 activation12-15.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Abstract
What the sources say
- Not checked yetcites [12] Hastie, N. D. et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, 866–868 (1990) source
- Not checked yetcites [13] Lee, H.-W. et al. Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574 (1998) source
- Not checked yetcites [14] Blasco, M. A. et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34 (1997) source
- Not checked yetcites [15] Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527–538 (1999) source
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In the paper
“We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Abstract
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In the paper
“We propose that telomere dysfunction-induced repression of the PGC network and consequent mitochondriopathy and metabolic changes, along with telomere-induced apoptotic and proliferative checkpoints, contributes to functional multi-system decline in the setting of telomere dysfunction.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Discussion
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In the paper
“p53 deficiency markedly attenuates the degenerative phenotypes associated with telomere dysfunction, whereas constitutively activated p53 accelerates ageing phenotypes15-18.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > p53 directly represses PGC-1α and PGC-1β
What the sources say
- Not checked yetcites [15] Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527–538 (1999) source
- Not checked yetcites [16] Wong, K. K. et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 421, 643–648 (2003) source
- Not checked yetcites [17] Maier, B. et al. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 18, 306–319 (2004) source
- Not checked yetcites [18] Tyner, S. D. et al. p53 mutant mice that display early ageing-associated phenotypes. Nature 415, 45–53 (2002) source
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In the paper
“The relevance of PGCs to age-related pathologies may stem from their regulation of mitochondrial biogenesis and control of metabolic processes (gluconeogenesis, fatty acid metabolism and β-oxidation), processes that relate to increased insulin resistance and diabetes in the aged9.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Abstract
What the sources say
- Not checked yetcites [9] Lin, J., Handschin, C. & Spiegelman, B. M. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 1, 361–370 (2005) source
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In the paper
“prompted by studies linking impaired mitochondrial function to defective HSC maintenance27-29”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
What the sources say
- Not checked yetcites [27] Pannicke, U. et al. Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. Nature Genet. 41, 101–105 (2008) source
- Not checked yetcites [28] Sankaran, V. G., Orkin, S. H. & Walkley, C. R. Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis. Genes Dev. 22, 463–475 (2008) source
- Not checked yetcites [29] Liu, J. et al. Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 459, 387–392 (2009) source
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In the paper
“Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Abstract
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In the paper
“Previous work has established that repression of either or both co-activators (PGC-1α or PGC-1β) decreases mitochondrial biogenesis and function, elicits cardiomyopathy and impairs de novo glucose production23-25.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > Telomere dysfunction induces pathophysiologies classical for impaired PGC function
What the sources say
- Not checked yetcites [23] Arany, Z. et al. Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-γ coactivator 1α. Proc. Natl Acad. Sci. USA 103, 10086–10091 (2006) source
- Not checked yetcites [24] Yoon, J. C. et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413, 131–138 (2001) source
- Not checked yetcites [25] Lai, L. et al. Transcriptional coactivators PGC-1α and PGC-lβ control overlapping programs required for perinatal maturation of the heart. Genes Dev. 22, 1948–1961 (2008) source
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“qPCR-based mitochondrial quantification was performed with two different primer sets for genomic and mitochondrial loci.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > METHODS SUMMARY
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“For chromatin immunoprecipitation, we followed the EZ-Chip protocol (Promega) using p53 specific antibody and control IgG.”
§ Telomere dysfunction induces metabolic and mitochondrial compromise > METHODS SUMMARY
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The paper relies on this without support.
N-acetylcysteine given from birth effectively scavenges reactive oxygen species in the haematopoietic stem cell compartments of G1 and G4 mice.
“G1 or G4 mice treated from birth with N-acetylcysteine, a ROS scavenger, did not rescue defective HSC repopulation in competitive transplantations”
The paper relies on this without support.
The G2 Terc−/− mice used have a degree of telomere dysfunction comparable to that of G4 Tert−/− mice.
“G2 Terc−/− liver and hearts (exhibiting comparable telomere dysfunction as G4 Tert−/− mice)”
The paper relies on this without support.
The transcriptomic network analyses used in this study were unbiased.
“These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta”
The paper relies on this without support.
The p53 binding elements identified in the PGC-1α and PGC-1β promoters are the functional sites through which p53 represses these genes.
“anti-p53 chromatin-immunoprecipitation assays in G2 Terc−/− p53+/+, but not G2 Terc−/− p53−/−, MEFs demonstrated physical binding between p53 and (1) PGC-1α fragments containing p53 binding elements at −564 and −954, but not −2317, and (2) PGC1β fragments containing p53 binding elements at −1616 and −1030”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“TERC−/− mice present altered mitochondrial functions, including increased production of reactive oxygen species (ROS) from the electron transfer chain (ETC) (Passos et al., 2010; Sahin et al., 2011).”
From P66SHC deletion improves fertility and progeric phenotype of late-generation TERC-deficient mice but not their short lifespan (2016) · cites this paper as Sahin et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, other mutations in genes involved in ROS metabolism, such as SOD2 haploinsufficiency, do not cooperate with telomere dysfunction (Guachalla et al., 2009), and the treatment with N‐acetylcysteine does not rescue progeric phenotypes of late‐generation TERT‐deficient mice (Sahin et al., 2011).”
From P66SHC deletion improves fertility and progeric phenotype of late-generation TERC-deficient mice but not their short lifespan (2016) · cites this paper as Sahin et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The increase in telomere length in quiescent/differentiated tissues could be related to prevention of stress-dependent telomere shortening (Sahin et al, 2011; Sharma et al, 2003), or to re-population of tissues by cells with longer telomeres (Hao et al, 2005).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Sahin et al, 2011
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In mouse models of accelerated telomere shortening, critically short telomeres have been shown to repress PGC1‐α‐ and β‐mediated mitochondrial biogenesis (Sahin et al, 2011; Chang et al, 2016).”
From Length-independent telomere damage drives post-mitotic cardiomyocyte senescence (2019) · cites this paper as Sahin et al, 2011
The cited source says what the claim attributes to it.
In the citing paper
“Although the rates of stem cell replenishment are unlike to completely account for the telomere length differences observed, we cannot discard other roles of telomerase such as the rescue of telomere shortening through stress protection (Saretzki, 2009) or the recently association to mitochondrial protection in post mitotic tissues (Sahin et al, 2011).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Sahin et al, 2011
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“our sample sizes are similar to those reported in previous publications.15,24,86”
From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [24]
Experimental — accuracy not yet measuredIn the citing paper
“signaling downstream of short telomeres activates p53, which binds and represses PGC-1α and PGC-1β promoters leading to mitochondrial dysfunction (Sahin et al., 2011).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Sahin et al., 2011
In the citing paper
“It is interesting that telomere dysfunction has been associated with changes in mitochondrial metabolism (93)”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [93]
In the citing paper
“more recently it has been recognized that telomere dysfunction causes prominent phenotypes in slow-turnover tissues97,99,100,103 (Table 2).”
From The telomere syndromes (2012) · cites this paper as [103]
In the citing paper
“The telomerase-knockout mouse has provided an important model for understanding telomere-mediated disease mechanisms because there is a remarkable convergence with human disease phenotypes (an overview is shown in Table 2)36,82,84,85,97,99–111.”
From The telomere syndromes (2012) · cites this paper as [103]
In the citing paper
“In these tissues, the metabolic dysfunction appears to be due to the effect of downregulation of PGC1α, which is a transcriptional co-activator that is important for mitochondrial biogenesis103.”
From The telomere syndromes (2012) · cites this paper as [103]
In the citing paper
“Shortened dysfunctional telomeres in other mouse cell types, such as cardiac myocytes and hepatocytes, have also been associated with decreased mitochondrial copy number and defective oxidative metabolism103.”
From The telomere syndromes (2012) · cites this paper as [103]
In the citing paper
“Recent findings correlate deficiency of TERT (and subsequent loss of telomeres) with deficiencies in mitochondrial function attributed to decreases in PGC-1α and PGC-1β expression and suppressed mitochondrial biogenesis (364).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [364]
In the citing paper
“p53 activation was found to suppress expression of the PGC-1α and PGC-1β (364), thus linking telomeres to mitochondrial biogenesis.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [364]
In the citing paper
“Cellular senescence is thought to further propagate nearby tissue aging through intracellular metabolic compromise (eg, mitochondrial dysfunction) (Sahin et al, 2011) and altered production of secretory factors that promote aging by increasing degradation of nearby tissue and sterile inflammation (Coppe et al, 2010a, b;Freund et al, 2010) (ie, senescence-associated secretory phenotype, SASP).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Sahin et al, 2011
In the citing paper
“For example, the tumor suppressor protein, p53, may be activated, which inhibits oxidative defense mechanisms (such as peroxisome proliferator-activated receptor-gamma coactivator [PGC] 1-α and β, promoting mitochondrial damage and senescence or apoptosis (Sahin et al., 2011) (Fig. 2).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Sahin et al., 2011
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“The importance of maintaining robust stem cell populations is demonstrated in mice with telomerase gene deletion.((95,97)) These mice develop senescent stem cell populations and have reduced capacity for tissue maintenance and regeneration.”
BackgroundInfluentialAir Pollution Stress and the Aging Phenotype: The Telomere Connection
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RAP1 Protects from Obesity through Its Extratelomeric Role Regulating Gene Expression
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“Telomere dysfunction owing to extreme telomere shortening is proposed to induce metabolic and mitochondrial compromise (Sahin et al., 2011).”
BackgroundInfluentialPieters, N., Janssen, B. G., Dewitte, H., Cox, B., Cuypers, A., Lefebvre, W., Smeets, K., Vanpoucke, C., Plusquin, M., & Nawrot, T. S. (2015) · Environmental Health Perspectives · doi:10.1289/ehp.1509728 · Cited by 125
“reported that mitochondrial changes associated with aging in telomere-deficient mice seemed to be driven by the combined suppression of peroxisome proliferator-activated receptor γ-coactivator1α (PPARGC1A) and peroxisome proliferator-activated receptor γ-coactivator1β (PPARGC1B) and their downstream targets [nuclear r…”
BackgroundInfluentialNon‐coding RNAs: the dark side of nuclear–mitochondrial communication
Vendramin, R., Marine, J., & Leucci, E. (2017) · The EMBO Journal · doi:10.15252/embj.201695546 · Cited by 123
“Telomere dysfunctions in mice are associated with impaired mitochondrial biogenesis and function through the repression of PGC1 a - and PGC1 b -driven programs by p53 (Sahin et al , 2011).”
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Mouse Models to Disentangle the Hallmarks of Human Aging
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“p53 deficiency in a telomerase deficient background improves gluconeogenesis and doxorubicin-induced cardiomyopathy in these mice.(156) Similarly, mitochondrial dysfunction has been observed in mouse models with defects in DNA repair, such as Xpa or Ercc6, where DNA damage activates PARP1 (poly-ADP-ribose polymerase 1…”
BackgroundLv, Y., Yang, Y., Sui, B., Hu, C., Zhao, P., Liao, L., Chen, J., Zhang, L., Yang, T.-T., Zhang, S., et al. (2018) · Theranostics · doi:10.7150/thno.23620 · Cited by 123
“senescence of stem cells, in which OXPHOS metabolism suffers from impairments, leading to less energy production but increased oxidative stress [27, 112].”
BackgroundCellular Senescence: Pathogenic Mechanisms in Lung Fibrosis
Parimon, T., Hohmann, M. S., & Yao, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126214 · Cited by 123
“Features of cellular senescence and IPF, for example, telomere shortening, DNA damage, which activates the DNA damage sensor poly[ADP- ribose] polymerase 1 (PARP-1) and p53, feedback to reduce activation of PPAR coactivators and reduce mitochondrial biogenesis [105].”
BackgroundNeurophysiological and epigenetic effects of physical exercise on the aging process
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Emerging Roles of p53 Family Members in Glucose Metabolism
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“These changes are dependent on p53 activation, which triggers the repression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and beta (PGC-1α and PGC-1β), which are positive master regulators of mitochondrial biogenesis [66].”
BackgroundSridharan, D. M., Asaithamby, A., Bailey, S. M., Costes, S. V., Doetsch, P. W., Dynan, W. S., Kronenberg, A., Rithidech, K. N., Saha, J., Snijders, A. M., et al. (2015) · Radiation Research · doi:10.1667/rr13804.1 · Cited by 124
Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells
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“More generally, the effect may be mediated by nontelomeric DNA damage, age, andmitochondrial integrity (13, 16, 42).”
BackgroundCellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity
Berlanga‐Acosta, J., Guillén, G. E., Rodríguez-Rodríguez, N., Mendoza‐Marí, Y., Bringas-Vega, M. L., Berlanga-Saez, J. O., Herrera, D. G. D. B., Martínez-Jiménez, I., Hernandez-Gutierrez, S., & Valdes-Sosa, P. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.573032 · Cited by 125
“It has been recently shown that telomeric damage activates a p53-dependent program which leads to mitochondrial failure via the repression of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) gene expression (78).”
BackgroundAge-associated telomere shortening in mouse oocytes
ヤマダ, ト., Yamada, M., Hamatani, T., Chikazawa-Nohtomi, N., Ogawa, S., Akutsu, H., Miura, T., Miyado, K., Tarín, J. J., Kuji, N., et al. (2013) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-11-108 · Cited by 117
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BackgroundPGC−1α Promoter Methylation in Parkinson’s Disease
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“Mitochondrial dysfunction is implicated in aging (1, 2) and in pathological processes, such as carcinogenesis (3) and inflammation (4, 5).”
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“In fact, its promoter contains several binding domains for many transcription factors [43], such as FoxO [44], MEF2 [45], ERRα [46], CREB [35] and p53 [36, 47].”
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“In this study, the authors describe a new link between telomere dysfunction and p53 activation, leading to mitochondrial and metabolic impairment through the repression of the master regulator of mitochondrial biogenesis, PGC-1α (peroxisome proliferator-activated receptor gamma, coactivator 1α) [8].”
BackgroundLinking the Metabolic State and Mitochondrial DNA in Chronic Disease, Health, and Aging
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“Such dysfunction can be associated with mitochondrial impairment and downregulation of the PGC-1α network, senescence, and apoptosis [110].”
BackgroundRECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity
Croteau, D. L., Rossi, M. L., Canugovi, C., Tian, J. Y., Sýkora, P., Ramamoorthy, M., Wang, Z.-M., Singh, D. K., Akbari, M., Kasiviswanathan, R., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00803.x · Cited by 112
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“These data are somehow in contrast with data showing that p53 activated by telomere dysfunction binds and represses PGC-1α promoter.(24) Thus, the interaction between p53 and PGC-1α appears to be specific to the cellular milieu.”
ResultThe Aging Lung and Idiopathic Pulmonary Fibrosis
Gulati, S., & Thannickal, V. J. (2019) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2019.02.008 · Cited by 109
Mitochondria, Telomeres and Telomerase Subunits
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“…out of the nucleus and imported into mitochondria, where it may have a protective role (Seimiya et al., 2000; Haendeler et al., 2003, 2004, 2009; Santos et al., 2004; Yan et al., 2004; Jakob et al., 2008; Maida et al., 2009; Kovalenko et al., 2010; Sharma et al., 2012; Singhapol et al., 2013;…”
BackgroundInfluentialA three-state model of telomere control over human proliferative boundaries
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Chromosomally integrated HHV-6: impact on virus, cell and organismal biology
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“Several diseases are linked to telomere dysfunctions and/or telomerase mutations such as hematopoietic dysfunction, pulmonary fibrosis, liver disease, degenerative diseases and cancer [49–59].”
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“Recent studies showed that telomere dysfunction including shortening is associated with impaired mitochondrial biogenesis and function, as well as increased ROS level [16].”
BackgroundInfluentialTelomere attrition: metabolic regulation and signalling function?
Casagrande, S., & Hau, M. (2019) · Biology Letters · doi:10.1098/rsbl.2018.0885 · Cited by 115
Bori, 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
DNA damage and mitochondria in cancer and aging
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Telomere shortening is a hallmark of genetic cardiomyopathies
Chang, A. C. Y., Chang, A. C. H., Kirillova, A., Sasagawa, K., Su, W., Weber, G., Lin, J., Termglinchan, V., Karakikes, I., Seeger, T., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714538115 · Cited by 91
“These murine models suggest that a telomere–mitochondrial axis is key to maintaining cardiac function and, in its absence, dilated cardiomyopathy leading to heart failure ensues (22, 23).”
Genomic Instability and Epigenetic Changes during Aging
López-Gil, L., Pascual‐Ahuir, A., & Proft, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814279 · Cited by 130
Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging
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Telomeres in aging and disease: lessons from zebrafish
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“Altogether, these events have been proposed to underlie dysfunction of more quiescent organs (e.g. heart) in G3/G4 Terc − / − /Tert − / − mice (Missios et al., 2014; Sahin et al., 2011).”
Mitochondrial Localization of Telomeric Protein TIN2 Links Telomere Regulation to Metabolic Control
Chen, L., Zhang, Y., Zhang, Q., Li, H., Luo, Z., Fang, H., Kim, S. H., Qin, L., Yotnda, P., Xu, J., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.07.002 · Cited by 109
Nontelomeric Role for Rap1 in Regulating Metabolism and Protecting against Obesity
Yeung, F., Ramírez, C. M., Mateos‐Gómez, P. A., Pinzaru, A. M., Ceccarini, G., Kabir, S., Fernandez-Hernando, C. F., & Sfeir, A. J. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.05.032 · Cited by 105
“Although this effect might be due to the activation of p53 at deprotected telomeres (Sahin et al., 2011), it is also possible that Rap1 could be the factor that relays themessage from the terminal structure to the rest of the genome.”
Rowe, G. C., Safdar, A., & Arany, Z. P. (2014) · Circulation · doi:10.1161/circulationaha.113.001590 · Cited by 107
“Recent data have also indicated that telomere shortening and p53 activation lead to repression of PGC-1α and mitochondrial capacity.(176) This observation links theories of aging and suggests that activation of PGC-1α by exercise may thus interfere with aging at this level also.”
TERT activation targets DNA methylation and multiple aging hallmarks
Shim, H. S., Iaconelli, J., Shang, X., Li, J., Lan, Z. D., Jiang, S., Nutsch, K., Beyer, B. A., Lairson, L. L., Boutin, A. T., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.048 · Cited by 104
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The role of PGC‐1 coactivators in aging skeletal muscle and heart
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The Length of the Shortest Telomere as the Major Determinant of the Onset of Replicative Senescence
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“In mammalian cells, mitochondrial dysfunction may also affect telomere-dependent senescence, and conversely telomeric signals may induce mitochondrial failure (20, 21).”
BackgroundNuclear respiratory factor 1 and endurance exercise promote human telomere transcription
Diman, A., Boros, J., Poulain, F., Rodriguez, J., Purnelle, M., Episkopou, H., Bertrand, L., Francaux, M., Deldicque, L., & Decottignies, A. (2016) · Science Advances · doi:10.1126/sciadv.1600031 · Cited by 101
Shorter Leukocyte Telomere Length in Midlife Women with Poor Sleep Quality
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The complex crosstalk between mitochondria and the nucleus: What goes in between?
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Role of PGC-1α in Vascular Regulation
Kadlec, A. O., Chabowski, D. S., Ait‐Aissa, K., & Gutterman, D. D. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307123 · Cited by 103
Non-canonical Roles of Telomerase: Unraveling the Imbroglio
Ségal-Bendirdjian, E., & Géli, V. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00332 · Cited by 106
Lara, P. C., Macías-Verde, D., & Burgos-Burgos, J. (2020) · Aging and Disease · doi:10.14336/ad.2020.0601 · Cited by 100
Harley, C. B., Liu, W., Flom, P. L., & Raffaele, J. M. (2013) · Rejuvenation Research · doi:10.1089/rej.2013.1430 · Cited by 102
Gravel, A., Dubuc, I., Morissette, G., Sedlak, R. H., Jerome, K. R., & Flamand, L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1502741112 · Cited by 98
Blättler, S. M., Verdeguer, F., Liesa, M., Cunningham, J. T., Vogel, R. O., Chim, H., Liu, H., Romanino, K., Shirihai, O. S., Vazquez, F., et al. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00337-12 · Cited by 100
Self-citationTelomere lengths in human pronuclei, oocytes and spermatozoa
Turner, S., & Hartshorne, G. M. (2013) · Molecular Human Reproduction · doi:10.1093/molehr/gat021 · Cited by 106
Chung, J., Khadka, P., & Chung, I. K. (2012) · Journal of Cell Science · doi:10.1242/jcs.099267 · Cited by 100
A free radical theory of frailty
Viña, J., Borrás, C., & Gómez‐Cabrera, M. C. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.028 · Cited by 97
“Central role of ROS in the proposed unified theory of aging [22] Deficiency in antioxidant enzymes expression does not”
BackgroundXia, W., Chen, H., Xie, C., & Hou, M. (2020) · Aging · doi:10.18632/aging.103136 · Cited by 99
“disruption during the senescence process [25].”
Integrating the Hallmarks of Aging Throughout the Tree of Life: A Focus on Mitochondrial Dysfunction
van der Rijt, S., Molenaars, M., McIntyre, R. L., Janssens, G. E., & Houtkooper, R. H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.594416 · Cited by 102
Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome
Lee, H., Oh, J. Y., Sung, Y., Chung, H., Kim, H., Kim, G. S., Cho, Y. S., & Kim, J. T. (2015) · Human Reproduction · doi:10.1093/humrep/deu352 · Cited by 98
“Telomere shortening can cause dysregulation of the insulin secretion, signaling pathway, mitochondrial function and Ca2+ metabolism (Guo et al., 2011; Sahin et al., 2011).”
BackgroundInterleukin-7 and Immunosenescence
Nguyen, V., Mendelsohn, A., & Larrick, J. W. (2017) · Journal of Immunology Research · doi:10.1155/2017/4807853 · Cited by 96
“Telomere attrition, DNA damage responses, mtDNA damage, and mitochondrial dysfunction are intimately connected to the metabolic changes associated with aging [73, 74].”
BackgroundSverdlov, A. L., Elezaby, A., Behring, J. B., Bachschmid, M. M., Luptak, I., Tu, V. H., Siwik, D. A., Miller, E. J., Liesa, M., Shirihai, O. S., et al. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.07.018 · Cited by 98
“5 μM) to avoid the reverse electron transfer effect [14].”
Self-citationTelomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria
Chiodi, I., & Mondello, C. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00133 · Cited by 98
Hutchinson–Gilford progeria syndrome through the lens of transcription
Prokocimer, M., Barkan, R., & Gruenbaum, Y. (2013) · Aging Cell · doi:10.1111/acel.12070 · Cited by 101
“Activation of p53 in HGPS also augments mitochondrial dysfunction and stem cells exhaustion in part by repressing the mitochondrial PGC1 protein (Halaschek-Wiener & Brooks-Wilson, 2007; Sahin & Depinho, 2010; Sahin et al., 2011).”
BackgroundMetabolic Plasticity of Tumor Cell Mitochondria
Cannino, G., Ciscato, F., Masgras, I., Sànchez‐Martìn, C., & Rasola, A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00333 · Cited by 97
“Nonetheless, under conditions of extreme stress p53 can have an opposite effect on mitochondria, potently contributing to their dysfunction through repression of the master regulators of mitochondrial biogenesis PGC-1α/PGC-1β, thus leading to cell senescence or death (82).”
BackgroundMechanisms of mitochondrial dysfunction in ovarian aging and potential interventions
Ju, W., Zhao, Y., Yu, Y., Zhao, S., Xiang, S., & Lian, F. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1361289 · Cited by 106
Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD
Lerner, C. A., Sundar, I. K., & Rahman, I. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.07.026 · Cited by 96
“Also, it has been recently shown that telomere compromised mouse tissues sustain impaired mitochondrial function (Sahin et al., 2011).”
BackgroundPGC1α repression in IPF fibroblasts drives a pathologic metabolic, secretory and fibrogenic state
Caporarello, N., Meridew, J. A., Jones, D. L., Tan, Q., Haak, A. J., Choi, K. M., Manlove, L. J., Prakash, Y. S., Tschumperlin, D. J., & Ligresti, G. (2019) · Thorax · doi:10.1136/thoraxjnl-2019-213064 · Cited by 97
Xiong, S., Patrushev, N. A., Forouzandeh, F., Hilenski, L. L., & Alexander, R. W. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.047 · Cited by 97
“TERT deficiency in mice exhibits dysfunction and shortening of telomeres, DNA damage, mitochondrial dysfunction and elevated oxidative stress (Sahin et al., 2011).”
BackgroundInfluentialMechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure
Gupte, A. A., Hamilton, D. J., Cordero‐Reyes, A. M., Youker, K. A., Yin, Z., Estep, J. D., Stevens, R. D., Wenner, B. R., Ilkayeva, O., Loebe, M. M., et al. (2014) · Circulation Cardiovascular Genetics · doi:10.1161/circgenetics.113.000404 · Cited by 94
“in other mouse models of increased cardiac P53 reversed these patterns and improved cardiac function.(18,43,45) Thus, it is pos-”
InfluentialNakamura, H., Matoba, S., Iwai‐Kanai, E., Kimata, M., Hoshino, A., Nakaoka, M., Katamura, M., Okawa, Y., Ariyoshi, M., Mita, Y., et al. (2011) · Circulation Heart Failure · doi:10.1161/circheartfailure.111.961565 · Cited by 97
The Protein Level of PGC-1α, a Key Metabolic Regulator, Is Controlled by NADH-NQO1
Adamovich, Y., Shlomai, A., Tsvetkov, P., Umansky, K. B., Reuven, N. B., Estall, J. L., Spiegelman, B. M., & Shaul, Y. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01672-12 · Cited by 99
“Recently, deactivation of the PGC-1 axis was linked to telomerase dysfunction, connecting the nuclear and mitochondrial aging processes with metabolism (10).”
BackgroundSystems biology approaches to adverse drug effects: the example of cardio-oncology
Brown, S.-A. N., Sandhu, N. P., & Herrmann, J. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.168 · Cited by 93
A short leucocyte telomere length is associated with development of insulin resistance
Verhulst, S., Dalgård, C., Labat, C., Kark, J. D., Kimura, M., Christensen, K., Toupance, S., Aviv, A., Kyvik, K. O., & Bénétos, A. (2016) · Diabetologia · doi:10.1007/s00125-016-3915-6 · Cited by 96
Lipofuscin causes atypical necroptosis through lysosomal membrane permeabilization
Pan, C., Banerjee, K., Lehmann, G. L., Almeida, D., Hajjar, K. A., Benedicto, I., Jiang, Z., Radu, R. A., Thompson, D. H., Rodriguez-Boulan, E. J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2100122118 · Cited by 96
Mitochondrial DNA copy number is reduced in male combat veterans with PTSD
Bersani, F. S., Morley, C., Lindqvist, D., Epel, E. S., Picard, M. A., Yehuda, R., Flory, J. D., Bierer, L. M., Makotkine, I., Amara, D. A., et al. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.06.012 · Cited by 93
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Aging and HIV/AIDS: pathogenetic role of therapeutic side effects
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The association between PGC-1α and Alzheimer's disease
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“PGC-1a controls the level of sirtuin1 [40] and sirtuin3 [41] which reduce the generation of ROS [10].”
BackgroundPGC1α: Friend or Foe in Cancer?
Mastropasqua, F., Girolimetti, G., & Shoshan, M. C. (2018) · Genes · doi:10.3390/genes9010048 · Cited by 97
“Inverse correlations between p53 and PGC1α have been observed also in non-cancer contexts, for example, upregulation of p53 due to telomere dysfunction repressed both PGC1α and PGC1β [59]; such mechanisms may turn out to be of interest in the cancer field.”
BackgroundAge-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease
Gao, Z., Daquinag, A. C., Fussell, C., Zhao, Z., Dai, Y., Rivera, A., Snyder, B. E., Eckel-Mahan, K. L., & Kolonin, M. G. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00320-4 · Cited by 92
How nutritional status signalling coordinates metabolism and lignocellulolytic enzyme secretion
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“The application of DTT or brefeldin A to T. reesei, decreases the mRNA level of secreted protein-encoding genes, including cellobiohydrolases and hydrophobins, but not the intracellular b-glucosidases (Saloheimo et al., 2002).”
Telomerase in Cancer: Function, Regulation, and Clinical Translation
Robinson, N. J., & Schiemann, W. P. (2022) · Cancers · doi:10.3390/cancers14030808 · Cited by 105
“At a molecular level, TERT acts synergistically with the master regulator of mitochondrial biogenesis, PCG-1α, thereby exerting direct transcriptional control over mitochondrial function [156].”
BackgroundStress and immunosenescence: The role of telomerase
de Punder, K., Heim, C. C., Wadhwa, P. D., & Entringer, S. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.10.019 · Cited by 95
“Telomerase is essential for normal mitochondrial production and function (Sahin et al., 2011).”
BackgroundMTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells
Bahat, A., Goldman, A., Zaltsman, Y., Khan, D. H., Halperin, C., Amzallag, E., Krupalnik, V., Mullokandov, M., Silberman, A., Erez, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07519-w · Cited by 90
Asnani, A. H., Moslehi, J. J., Adhikari, B. B., Baik, A. H., Beyer, A., de Boer, R. A., Ghigo, A., Grumbach, I. M., Jain, S. S., & Zhu, H. (2021) · Circulation Research · doi:10.1161/res.0000000000000473 · Cited by 94
Self-citationMitochondrial dysfunction: a neglected component of skin diseases
Feichtinger, R. G., Sperl, W., Bauer, J. W., & Kofler, B. (2014) · Experimental Dermatology · doi:10.1111/exd.12484 · Cited by 94
Mitochondrial DNA Copy Number and Exposure to Polycyclic Aromatic Hydrocarbons
Pavanello, S., Dioni, L., Hoxha, M., Fedeli, U., Mielżyńska‐Švach, D., & Baccarelli, A. (2013) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-13-0118 · Cited by 89
“reduction of mitochondrial function and mtDNAcn (46).”
BackgroundSantulli, G., Ciccarelli, M., Trimarco, B., & Iaccarino, G. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00209 · Cited by 86
“…fails to distinguish self from nonself antigens (Menconi et al., 2008); others relate aging to the loss of epigenetic controls, including but not limited to DNA methylation, or to detrimental effects of toxic chemicals (Sahin et al., 2011; Akbarian et al., 2013; Santulli and Totary-Jain, 2013).”
BackgroundCellular Senescence: The Trojan Horse in Chronic Lung Diseases
Hamsanathan, S., Alder, J. K., Sellarés, J., Rojas, M. M., Gurkar, A. U., & Mora, A. L. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2018-0410tr · Cited by 89
Fine-Tuning of PGC1α Expression Regulates Cardiac Function and Longevity
Zhu, X., Shen, W., Yao, K., Wang, H., Лю, Б., Li, T., Song, L., Diao, D., Mao, G., Huang, P., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.315529 · Cited by 88
Metadata
- Authors
- Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., Walkey, C., Maser, R. S., Tonon, G., Foerster, F., Xiong, R., Wang, Y. A., Shukla, S. A., Jaskelioff, M., Martin, E. S., Heffernan, T. P., Protopopov, A., Ivanova, E., Mahoney, J. E., Kost-Alimova, M., Perry, S. R., Bronson, R., Liao, R., Mulligan, R., Shirihai, O. S., Chin, L., & DePinho, R. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Harvard University (US)
- Boston University (US)
- Brigham and Women's Hospital (US)
- University of Massachusetts Chan Medical School (US)
- The University of Melbourne (AU)
- Corresponding author
- DePinho, Ronald A.
- ORCID
- Sahin, Ergün
- Colla, Simona
- Liesa, Marc
- Moslehi, Javid
- Müller, Florian L.
- Kotton, Darrell
- Walkey, Carl
- Tonon, Giovanni
- Foerster, Friedrich
- Wang, Y. Alan
- Shukla, Sachet A.
- Jaskelioff, Mariela
- Martin, Eric S.
- Heffernan, Timothy P.
- Protopopov, Alexei
- Ivanova, Elena
- Mahoney, John E.
- Bronson, Roderick
- Liao, Ronglih
- Shirihai, Orian S.
- DePinho, Ronald A.
- Venue
- Nature
- Published
- 2011-02-09
- Volume
- 470
- Issue
- 7334
- Pages
- 359-365
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3741661
- OpenAlex
- W2124098526
- Semantic Scholar
- 14115a60df726b2a29c3a0b4d83e9f284c2371bb
- Cited by
- 1,319
- References
- 49
- Citations by year
- 2026: 50 · 2025: 58 · 2024: 73 · 2023: 87 · 2022: 83 · 2021: 100 · 2020: 78 · 2019: 84 · 2018: 81 · 2017: 88 · 2016: 91 · 2015: 93 · 2014: 83 · 2013: 94 · 2012: 111
- FWCI
- 76.58
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-06-22)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- National Cancer Institute (R01CA084628)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK035914, R01DK089185, U24DK59635, P30DK046200, U24DK059635, R01DK063356, R01DK056690, P30DK079638)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- telomere dysfunction, p53, PGC-1α, PGC-1β, telomerase reverse transcriptase, telomerase RNA, mitochondrial biogenesis, mitochondrial dysfunction, gluconeogenesis, cardiomyopathy, reactive oxygen species, cellular senescence, hematopoietic stem cells, liver, heart, aging, transcriptional repression
- MeSH terms
- Adenosine Triphosphate, Aging, Animals, DNA, Mitochondrial, Doxorubicin, Gluconeogenesis, Hematopoietic Stem Cells, Liver, Mitochondria, Cardiomyopathies, Myocardium, RNA, Transcription Factors, Tumor Suppressor Protein p53, Telomere, Reactive Oxygen Species, Telomerase, Cell Proliferation, Mice
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