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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
“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]
The 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
“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
Citations
Cites
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · cited 1×
“In summary, combined biochemical, genetic and physiological results indicate that (1) activated p53 directly represses PGC-1a and PGC1b, (2) p53 deficiency alleviates transcriptional repression and associated decline in mitochondrial DNA content in tissues and cells with telomere dysfunction, and (3) p53 deficiency pa…”
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · cited 2×
“Finally, 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 (Fi…”
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734
Metabolic control through the PGC-1 family of transcription coactivators
Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130
Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108
Self-citationUnderstanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984 · cited 2×
“Finally, 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 (Fi…”
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650
p53 Regulates Mitochondrial Respiration
Matoba, S., Kang, J.-G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., & Hwang, P. M. (2006) · Science · doi:10.1126/science.1126863 · Cited by 1,650
Cited by
Sorted by citations
Items 801–900 of 999
Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment
Maeda, H., Kami, D., Maeda, R., Shikuma, A., & Gojo, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-90316-1 · Cited by 16
“Telomere attrition activates p53, which leads to the suppression of Pgc1α/β, nuclear respiratory factor 1, estrogen-related receptor α, and Pparα, consequently resulting in inhibition of mitochondriogenesis and mitochondrial dysfunction(Sahin et al, 2011).”
BackgroundBima, A. I. H., Eldakhakhny, B. M., Nuwaylati, D. A., Alnami, A., Ajabnoor, M. A., & Elsamanoudy, A. Z. (2021) · Nutrients · doi:10.3390/nu13114127 · Cited by 18
Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming
Chen, R., & Skutella, T. (2022) · Cells · doi:10.3390/cells11050830 · Cited by 15
“Abnormal telomere function inhibits PGC-1α and its downstream gene network via the p53-PGC pathway, thereby affecting cellular metabolism, causing organ dysfunction and leading to ageing [41].”
BackgroundRole of fruits in aging and age-related disorders
Arif, M. U., Khan, M. K. I., Riaz, S., Nazir, A., Maan, A. A., Amin, U., Saeed, F., & Afzaal, M. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111763 · Cited by 17
Kong, Q., Yan, X., Cheng, M., Jiang, X. M., Xu, L., Shen, L., Yu, H., & Sun, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063290 · Cited by 16
“found that telomere damage induces p53-mediated transcriptional repression of the expression of PGC-1α and PGC-1β, thereby inhibiting the transcription of PGC-1α transcriptional targets including transcription factor A, mitochondrial (TFAM) in various mouse tissues [24].”
BackgroundZhang, R., Du, J., Xiao, Z., Jiang, Y., Jin, L., & Weng, Q. (2022) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-022-04801-0 · Cited by 17
“The mechanism of this association remains to be determined; mitochondrial effects of p53 activation from telomere dysfunction [7] and TERT effects on mtDNA repair may be involved [62].”
BackgroundLiu, Z., Wan, P., Duan, H., Zhou, J. L., Tan, B., Liu, Y., Zhou, Q., Zhou, C., Huang, Z., Tian, B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053576 · Cited by 15
Wiley, L., Ashok, D., Martin-Ruiz, C. M., Talbot, D. C. S., Collerton, J. C., Kingston, A., Davies, K., Chinnery, P. F., Catt, M., Jagger, C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091005 · Cited by 15
Lee, J., Kim, J., & Lee, D. (2017) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000480427 · Cited by 15
Ectopic expression of telomerase safely increases health span and life span
Mendelsohn, A. R., & Larrick, J. W. (2012) · Rejuvenation Research · doi:10.1089/rej.2012.1359 · Cited by 14
Said, A. A., Nasr, Y., Galal, A. A. A., Abdelhamid, A. E.-S., Mohamed, H. A., Metwally, M. M. M., Said, M. A., NASSAN, M. A., Dahran, N. A., & Mohamed, A. A.-R. (2022) · Life · doi:10.3390/life12050639 · Cited by 14
“The peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) performs a vital role in mitochondrial function and biogenesis control, including oxidative phosphorylation and reactive oxygen species detoxification [55].”
BackgroundLi, W., Zhang, Y., Wang, X., Cao, J., Qian, W., Ling, G., Tan, N., Jiang, J., Sun, Q., Li, C., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/4344677 · Cited by 14
“PGC-1 α plays a central role in a regulatory network positively governing the transcriptional control of mitochondrial bio-genesis and respiratory function [18].”
Self-citationLinks between telomere dysfunction and hallmarks of aging
Li, S., Liu, Z., Zhang, J., & Li, L. (2023) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2023.503617 · Cited by 15
Shen, Y., Kim, I., Weintraub, N. L., & Tang, Y. (2023) · Cardiology Plus · doi:10.1097/cp9.0000000000000038 · Cited by 14
“Mitochondrial OXPHOS yields as a byproduct reactive oxygen species (ROS), which in turn can damage mitochondrial DNA, impair respiratory chain function, and lead to nuclear DNA damage[16,17].”
BackgroundTelomere dysfunction in chronic liver disease: The link from aging
Penrice, D. D., Jalan‐Sakrikar, N., Jurk, D., Passos, J. F., & Simonetto, D. A. (2023) · Hepatology · doi:10.1097/hep.0000000000000426 · Cited by 14
“[23,50] Indeed, transcriptomic analyses reveal suppression of Peroxisome proliferator-activated receptor-γ coactivator (PGC1) genes ( α and β ) through a p53-dependent mechanism showing declining mitochondrial function and increased oxidative damage.”
Grady, C. I., Walsh, L. M., & Heiss, J. D. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1154753 · Cited by 14
Mitonuclear Communication in Stem Cell Function
Peng, B., Wang, Y., & Zhang, H. (2024) · Cell Proliferation · doi:10.1111/cpr.13796 · Cited by 14
“This protein then binds to and inhibits the promoters of PGC-1α and PGC-1β, establishing a connection between mitochondrial function and telomere integrity [157].”
Self-citationLi, W., Zhang, Y., Yan, W., Ling, G., Zhang, Y., Li, Y., Guo, S., Tan, N., Ma, L., Li, W., et al. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.103810 · Cited by 14
“PGC-1α plays a central role in a regulatory network positively governing the transcriptional control of mitochondrial biogenesis and respiratory function [77, 79].”
Self-citationTelomere dysfunction and cell cycle checkpoints in hematopoietic stem cell aging
Ju, Z., Zhang, J., Gao, Y., & Cheng, T. (2011) · International Journal of Hematology · doi:10.1007/s12185-011-0882-z · Cited by 14
Oxidative Stress in the Aging Process: Fundamental Aspects and New Insights
del Valle, L. G., Hernández, R. G., Roche, L. D., & Fernández, O. (2015) · ACS symposium series · doi:10.1021/bk-2015-1200.ch006 · Cited by 15
Short telomeres — A hallmark of heritable cardiomyopathies
Chang, A. C. Y., & Blau, H. M. (2018) · Differentiation · doi:10.1016/j.diff.2018.02.001 · Cited by 15
Negative Association of Serum Uric Acid with Peripheral Blood Cellular Aging Markers
Yu, J., Liu, H., He, S., Li, P., Ma, C., Ping, F., Zhang, H., Li, W., Sun, Q., Ma, M., et al. (2019) · The journal of nutrition health & aging · doi:10.1007/s12603-019-1200-3 · Cited by 15
“On the other hand, telomere dysfunction activates P53 protein expression, which in turn inhibits the expression of peroxisome proliferator-activated receptor-C coactivator-1α (PGC-1α), decreases mitochondrial function, and promotes senescence (16).”
HuB and HuD repress telomerase activity by dissociating HuR from TERC
Cheng, X., Gu, X., Xia, T., Ma, Z., Yang, Z., Feng, H. L., Zhao, Y. B., Ma, W., Ju, Z., Gorospe, M., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab062 · Cited by 14
Hyun, D., & Lee, J. (2021) · Antioxidants · doi:10.3390/antiox11010007 · Cited by 15
“PGC1α/β are involved in mitochondrial biogenesis, and their low levels are the key connectors between defective mitochondria and telomere shortening [104].”
BackgroundWomen at heart: Introducing gender cardio-oncology
Canale, M. L., Bisceglia, I., Gallucci, G., Russo, G., Camerini, A., Fusco, S. A. D., Paccone, A., Camilli, M., Fiscella, D., Lestuzzi, C., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.974123 · Cited by 14
“This effect may be amplified in older female patients, but in the near future this toxic “senescent status” of cells may be targeted and reversed and this fact could reduce the burden of anthracycline-induced cardiotoxicity (110, 111).”
BackgroundSugden, M. C., & Holness, M. J. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00090.2012 · Cited by 14
Telomeres and stress: Promising avenues for research in psycho-oncology
Law, E., Girgis, A., Sylvie, L., Levesque, J. V., & Pickett, H. A. (2016) · Asia-Pacific Journal of Oncology Nursing · doi:10.4103/2347-5625.182931 · Cited by 14
“It is well-established that telomere length is both a marker and potential mechanism of cellular ageing.([65,66]) Shortened leukocyte telomere length has been linked to numerous agerelated diseases, such as increased cancer risk,([64,67]) diabetes, cardiovascular disease, and dementia.”
BackgroundAnti‐ageing effect of red ginseng revealed by urinary metabonomics using RRLC‐Q‐TOF‐MS
Sun, J., Jiao, C., Ma, Y., Chen, J., Wu, W., & Liu, S. (2018) · Phytochemical Analysis · doi:10.1002/pca.2758 · Cited by 14
The relation of telomere length at midlife to subsequent 20‐year depression trajectories among women
Gillis, J. C., Chang, S., Wang, W., Simon, N. M., Normand, S. T., ROSNER, B. A., Blacker, D., Vivo, I. D., & Okereke, O. I. (2019) · Depression and Anxiety · doi:10.1002/da.22892 · Cited by 15
“…stress, and mitochondrial dysfunction via a p53‐mediated process; this may lead to further downstream mitochondrial and metabolic dysfunction, including among postmitotic cells that are energy demand‐sensitive (Hovatta, 2015; Sahin et al., 2011; Verhoeven et al., 2014; Wolkowitz et al., 2015).”
BackgroundUchiumi, F., Fujikawa, M., Miyazaki, S., & Tanuma, S. (2013) · AIMS molecular science · doi:10.3934/molsci.2013.1.1 · Cited by 14
“Dysfunction or shortening of mammalian telomeres causes p53-mediated suppression of PGC-1, which in turn causes mitochondrial dysfunction to overproduce reactive oxygen species (ROS) [64].”
Christensen, K., Pedersen, J. K., Hjelmborg, J., Vaupel, J. W., Stevnsner, T., Holm, N. V., & Skytthe, A. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls087 · Cited by 13
Carroll, J., Olmstead, R. E., Cole, S. W., Breen, E. C., Arevalo, J. M. G., & Irwin, M. R. (2023) · GeroScience · doi:10.1007/s11357-023-00741-5 · Cited by 13
“Of note, our marker of cellular senescence captures aging within the circulating immune system, which has implications for immunity [17–21], but may also contribute to aging processes across other tissues in the body [17, 19, 22, 23], and be a link to chronic disease and death [24–26].”
BackgroundGinsenoside F1-Mediated Telomere Preservation Delays Cellular Senescence
Hou, J., Yun, Y. J., Jeon, B.-M., Baek, J.-I., & Kim, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241814241 · Cited by 16
“It is worth noting that previous research has documented that shortened telomeres can suppress the expression of the PGC-1 family of coactivators, potentially resulting in perturbed mitochondrial function [29].”
BackgroundTumor viruses and replicative immortality – Avoiding the telomere hurdle
Chen, X., Kamranvar, S. A., & Masucci, M. G. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.01.006 · Cited by 14
HSP27 role in cardioprotection by modulating chemotherapeutic doxorubicin-induced cell death
Ramani, S., & Park, S. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02048-4 · Cited by 13
Martin, H., Doumic, M., Teixeira, M. T., & Xu, Z. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00693-3 · Cited by 13
Relative Telomere Length Is Associated With Age-Related Macular Degeneration in Women
Koller, A., Brandl, C., Lamina, C., Zimmermann, M. E., Summerer, M., Stark, K. J., Würzner, R., Heid, I. M., & Kronenberg, F. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.5.30 · Cited by 13
“42 Generally, PGC-1 α reduces oxidative stress and senescence and in contrast supports proteostasis and telomerase (reviewed in Reference 43).”
RAP1: Protector of Telomeres, Defender against Obesity
Duong, M. T., & Sahin, E. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.011 · Cited by 13
Self-citationUchiumi, F., Shoji, K., Sasaki, Y., Sasaki, M., Sasaki, Y., Oyama, T., Sugisawa, K., & Tanuma, S.-I. (2015) · The Journal of Biochemistry · doi:10.1093/jb/mvv126 · Cited by 13
“Furthermore, it has been suggested that cross-talk between telomeres and mitochondria plays a role in the regulation of aging (6, 7).”
BackgroundImpairment of fetal hematopoietic stem cell function in the absence of Fancd2
Suzuki, S., Racine, R. R., Manalo, N. A., Cantor, S. B., & Raffel, G. D. (2016) · Experimental Hematology · doi:10.1016/j.exphem.2016.11.006 · Cited by 13
Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells
Cheng, Z., Peng, H., Zhang, R., Fu, X., & Zhang, G. (2017) · Rejuvenation Research · doi:10.1089/rej.2017.1930 · Cited by 13
“39 It was observed in our experiments that telomere length was not significantly different between cardiac tissues harvested from newborn, adult, and aged mice, which may have been caused by maintenance of telomerase activity in aged rodents.”
Female Genomics: Infertility and Overall Health
Joshi, N., & Chan, J. L. (2017) · Seminars in Reproductive Medicine · doi:10.1055/s-0037-1603095 · Cited by 13
Is Telomere Length a Biomarker of Neurological Disorders?
Thanseem, I., Viswambharan, V., Poovathinal, S. A., & Anitha, A. (2017) · Biomarkers in Medicine · doi:10.2217/bmm-2017-0032 · Cited by 14
Knez, J., Lakota, K., Božič, N., Okrajšek, R., Cauwenberghs, N., Thijs, L., Kneževič, I., Vrtovec, B., Tomšič, M., Čučnik, S., et al. (2017) · Genetic Testing and Molecular Biomarkers · doi:10.1089/gtmb.2017.0099 · Cited by 12
“Experimental studies demonstrated that induced disturbances in mtDNA replication and, therefore, in mtDNA copy numbers in cardiomyocytes, can cause dilated cardiomyopathy (DCM) in mice (Wang et al. , 1999; Hansson et al. , 2004; Trifunovic et al. , 2004; Lewis et al. , 2007; Sahin et al. , 2011).”
Zhang, Y., Shao, C., Li, H., Wu, K., Gong, L., Zheng, Q., Dan, J., Jia, S., Tang, X., Wu, X., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.597566 · Cited by 13
Genetics: Dynamic Cellular Aging Markers Associated with Major Depression
Hovatta, I. (2015) · Current Biology · doi:10.1016/j.cub.2015.03.036 · Cited by 13
Peripheral Blood Mitochondrial DNA and Myocardial Function
Kuznetsova, T., & Knez, J. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55330-6_19 · Cited by 14
Telomeres and Mitochondrial Function
Finkel, T. (2011) · Circulation Research · doi:10.1161/res.0b013e31821bc2d8 · Cited by 13
Giorgio, M., Stendardo, M., Migliaccio, E., & Pelicci, P. G. (2016) · Aging Cell · doi:10.1111/acel.12448 · Cited by 11
Telomere length and mitochondrial DNA copy number in multidrug-resistant tuberculosis
Freimane, L., Barkāne, L., Igumnova, V., Kivrāne, A., Zole, E., & Ranka, R. (2021) · Tuberculosis · doi:10.1016/j.tube.2021.102144 · Cited by 12
PGC ‐1α attenuates TNF ‐α‐induced inflammatory responses in OCCM ‐30 cells
Fu, Y., Du, M., Cao, Z., & He, H. (2022) · Journal of Periodontal Research · doi:10.1111/jre.13042 · Cited by 12
Astrocyte-derived apolipoprotein D is required for neuronal survival in Parkinson’s disease
Dai, Y., Bi, M., Jiao, Q., Du, X., Yan, C., & Jiang, H. F. (2024) · npj Parkinson s Disease · doi:10.1038/s41531-024-00753-8 · Cited by 11
“TAp73 -KO mice show increased ROS production and oxidative stress sensitivity 68 .”
Knez, J., Cauwenberghs, N., Thijs, L., Winckelmans, E., Brguljan-Hitij, J., Yang, W., Staessen, J. A., Nawrot, T. S., & Kuznetsova, T. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.03.090 · Cited by 12
Telomere length and age-dependent telomere attrition: the blood-and-muscle model
Chahine, M. N., Toupance, S., El-Hakim, S., Labat, C., Gautier, S., Moussallem, T., Yared, P., Asmar, R. G., & Bénétos, A. (2019) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2018-0582 · Cited by 12
Chen, Y., Jiang, F., Kong, G., Yuan, S., Cao, Y., Zhang, Q., Wang, Q., & Liu, L. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9926284 · Cited by 12
“Herein, we also observed that the administration of bleomycin could decrease the protein level of TERT, one critical component of telomerase [36, 37], and which might be associated with telomere shortening during the process of cellular senescence.”
BackgroundNiu, Z., Wen, X., Buka, S. L., Wang, M., Tian, L., Loucks, E. B., Kubzansky, L. D., & Mu, L. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.08.013 · Cited by 12
Liu, C., Chen, Y., Sun, B., Chen, H., Mustieles, V., Messerlian, C., Sun, Y., Meng, T., Lu, W., Pan, X., et al. (2022) · Environmental Research · doi:10.1016/j.envres.2022.114737 · Cited by 12
Self-citationHuang, W., Zhou, W., Li, C., Yang, Y., Shang, Y., Chen, C., Zhang, J., Yao, R., Wang, P., Wen, W., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15458 · Cited by 13
“The study on TERT knockout mice reveals that telomere dysfunction is associated with decreased gluconeogenesis [36].”
Qiu, G., Zheng, X., Fu, M., Huang, C., & Yang, X. (2019) · Biogerontology · doi:10.1007/s10522-019-09832-3 · Cited by 13
Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD
Casas-Recasens, S., Mendoza, N., López-Giraldo, A., Garcia, T., Cosío, B. G., Pascual-Guàrdia, S., Castro-Acosta, A. A., Borràs-Santos, A., Gea, J., Garrabou, G., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.761767 · Cited by 12
“Whereas, mitochondrial dysfunction cause telomere attrition (51), telomere dysfunction activates the DNA damage response (p53) and leads to the repression of PGC-1α/PGC-1β and their downstream targets, that in turn drive a mitochondria biogenesis decline (52) and mitochondrial dysfunctions (11).”
BackgroundPlacental mtDNA copy number and methylation in association with macrosomia in healthy pregnancy
Lin, X.-J., Xu, X., Zhang, H.-X., Ding, M., Cao, W.-Q., Yu, Q., Wang, Y., Yan, H., & Yang, X. (2021) · Placenta · doi:10.1016/j.placenta.2021.12.021 · Cited by 12
Self-citationFrosch, D. L., Saxbe, D., Tomiyama, A. J., Glenn, B. A., Low, C. A., Hanoch, Y., Motivala, S. J., & Meeker, D. (2010) · Health Psychology · doi:10.1037/a0020750 · Cited by 12
Öztürk, S. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111913 · Cited by 11
Zong, Y., Yang, Y., Zhao, J., Li, L., Luo, D., Hu, J., Gao, Y., Xie, X., Shen, L., Chen, S., et al. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.108511 · Cited by 13
The crosstalk between glucose metabolism and telomerase regulation in cancer
Huang, M., Liu, M., Wang, R., Man, Y., Zhou, H., Xu, Z., & Wang, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116643 · Cited by 11
Self-citationExploring potential pathways from oxidative stress to ovarian aging
Kobayashi, H., & Imanaka, S. (2024) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.16166 · Cited by 13
“Sahin et al. 88 demonstrated that telomere damage activates p53, suppresses PGC-1 α and PGC-1 β expression, reduces mitochondrial number and mtDNA copy number, and induces senescence through cell cycle arrest.”
Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase
Šimoničová, L., Dudekova, H., Ferenc, J., Procházková, K., Neboháčová, M., Dušinský, R., Nosek, J., & Tomáška, Ľ. (2015) · Current Genetics · doi:10.1007/s00294-014-0472-8 · Cited by 12
“Keywords Telomerase · Mitochondria · Yeast · Oxidative stress”
BackgroundDekker, P., van Baalen, L. M., Dirks, R. W., Slagboom, P. E., van Heemst, D., Tanke, H. J., Westendorp, R. G. J., & Maier, A. B. (2011) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr196 · Cited by 11
Mitochondrial Markers in Aging and Primary Open-Angle Glaucoma
Liu, H., Mercieca, K., & Prokosch, V. (2020) · Journal of Glaucoma · doi:10.1097/ijg.0000000000001448 · Cited by 10
Wang, B., Fan, L., Yang, S., Zhou, M., Mu, G., Liu, W., Yu, L., Yang, M., Cheng, M., Wang, X., et al. (2022) · Environmental Pollution · doi:10.1016/j.envpol.2022.120147 · Cited by 11
Telomerase as a possible key to bypass reproductive cost
Frydrychová, R. Č. (2023) · Molecular Ecology · doi:10.1111/mec.16870 · Cited by 12
“2007), or that telomere shortening and dysfunction can lead to alterations in mitochondrial functioning (Guo et al. 2011; Sahin et al. 2011).”
BackgroundLi, K., Dai, M., Sacirovic, M., Zemmrich, C., Pagonas, N., Ritter, O., Grisk, O., Lubomirov, L. T., Lauxmann, M. A., Bramlage, P., et al. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1157571 · Cited by 12
“Indeed, telomeres and mitochondria play critical roles in premature biological aging (6) and aging-related CVD (7).”
BackgroundInfluentialMitochondria and telomeres: hand in glove
Vaurs, M., Dolu, E. B., & Decottignies, A. (2023) · Biogerontology · doi:10.1007/s10522-023-10074-7 · Cited by 11
“In mouse models of telomerase deficiency, telomere dysfunction, though the p53-PGC1α/β axis, was reported to induce mitochondrial dysfunction (Sahin et al. 2011), suggesting a feedforward loop between dysfunctional telomeres and mitochondria.”
Raymond, A. R., Becker, J. R., Woodiwiss, A. J., Booysen, H. L., Norton, G. R., & Brooksbank, R. L. (2015) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2015.06.013 · Cited by 11
“Possible consequences of telomere attrition are cardiomyocyte apoptosis and premature senescence and the repression of mitochondrial biogenesis.(11,12) Therefore, telomere attrition may be a fundamental mechanism responsible for the development of adverse cardiac remodeling (dilation) and dysfunction.”
Uchiumi, F., Arakawa, J., Iwakoshi, K., Ishibashi, S., & Tanuma, S.-I. (2016) · Scientific Reports · doi:10.1038/srep24510 · Cited by 12
Age‑related changes in mineralocorticoid receptors in rat hearts
Hu, D., Dong, R., Zhang, Y., Yang, Y., Chen, Z., Tang, Y., Fu, M., Xu, X., & Tu, L. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11260 · Cited by 11
“PGc-1α drives all aspects of mitochondrial biogenesis and cardiac function, including mitochondrial number, mitochondrial respiration and roS levels (24-27).”
BackgroundZhang, L., Lu, Y., Ma, X., Xing, Y., Sun, J., & Jia, Y. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.965924 · Cited by 11
“For example, telomere inactivation can activate p53, which leads to DNA damage and DNA repair at the end of chromosomes (Sahin et al., 2011), meanwhile, the p53–p21–DREAM–E2F/CHR pathway, in turn, downregulates telomere maintenance and influence telomere homeostasis in cancer (Engeland, 2018; Vodicka et al.”
BackgroundMendelsohn, A. R., & Larrick, J. W. (2015) · Rejuvenation Research · doi:10.1089/rej.2015.1780 · Cited by 11
“7 On the basis of previous work in which TERT deficiency reduced PGC-1 a expression, 3 Xiong et al. hypothesized that levels of TERT, which is known to be expressed in vascular smooth muscle cells, would be reduced.”
Amodeo, V., Davies, T. J., Martínez-Segura, A., Clements, M., Ragdale, H. S., Bailey, A., dos Santos, M. S., MacRae, J. I., Mokochinski, J. B., Kramer, H., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.03.021 · Cited by 15
Xie, S., Li, M., Jiang, F., Qian, Y., & Yang, W. (2023) · PubMed Central · doi:10.12122/j.issn.1673-4254.2023.05.02 · Cited by 10
Mitochondrial Dysfunction: A Roadmap for Understanding and Tackling Cardiovascular Aging
Zhang, H., Muhetarijiang, M., Chen, R. J., Hu, X., Han, J., Zheng, L., & Chen, T. (2024) · Aging and Disease · doi:10.14336/ad.2024.0058 · Cited by 12
“This cascade ultimately culminates in mitochondrial dysfunction, as observed in age-related heart failure in both mice and humans [131].”
Coumarins at the Crossroads of Drug Development: Enzyme Modulation for Clinical Advances
Mustafa, Y. F. (2025) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-025-01331-2 · Cited by 10
Alshinnawy, A. S., El-Sayed, W. M., Sayed, A. A., Salem, A. M. H., & Taha, A. M. (2021) · Europe PMC (PubMed Central) · doi:10.22038/ijbms.2021.56670.12655 · Cited by 10
“Telomere dysfunction mainly impacts the G1 phase via activating the DNA damage response checkpoints (5).”
BackgroundMitochondrial Metabolism in X-Irradiated Cells Undergoing Irreversible Cell-Cycle Arrest
Hirose, E., Noguchi, M., Ihara, T., & Yokoya, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031833 · Cited by 12
“[39] revealed the presence of mitochondrial dysfunction in mice that were engineered to progressively lose telomere function.”
BackgroundImmune mechanisms of cardiac aging
Goldstein, D. R., & Abdel‐Latif, A. (2023) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.02 · Cited by 10
“All of these age-related pathophysiological changes collectively lead to a chronic low-inflammatory state that affects both the innate and adaptive immune systems [25] .”
BackgroundTHE THEORIES OF AGING: REACTIVE OXYGEN SPECIES AND WHAT ELSE?
Avantaggiato, A., Bertuzzi, G., Pascali, M., Candotto, V., & Carinci, F. (2015) · PubMed · Cited by 10
Pang, Q., Qian, D., Cheng, J., Ding, X., Chen, X., Chen, X., Guan, Y., Zhang, B., Wang, J., Er, P., et al. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s103141 · Cited by 10
Hainaut, P. L., Wiman, K. G., & Olivier, M. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3676-8 · Cited by 10
TZAP‐ing telomeres down to size
García-Expósito, L., & O’Sullivan, R. J. (2017) · EMBO Reports · doi:10.15252/embr.201744354 · Cited by 10
Training Performed Above Lactate Threshold Decreases p53 and Shelterin Expression in Mice
Cunha, V. D. C., Rosa, T. D. S., Sales, M. M., Sousa, C. V., Aguiar, S. D. S., Deus, L. A., Simões, H. G., & de Andrade, R. (2018) · International Journal of Sports Medicine · doi:10.1055/a-0631-3441 · Cited by 11
“It is important to note that p53 plays a different role in cell nucleus compared to the mitochondria, since it can also be identified as a mitochondrial integrity regulator [35, 39, 48], stabilizing mitochondrial DNA [1].”
BackgroundNew drugs for pharmacological extension of replicative life span in normal and progeroid cells
Vatolin, S., Radivoyevitch, T., & Maciejewski, J. P. (2019) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-018-0032-4 · Cited by 10
Melicher, D., Illés, A., Littvay, L., Tárnoki, Á. D., Tárnoki, D. L., Bikov, A., Kunos, L., Csabán, D., Buzás, E. I., Molnár, M. J., et al. (2019) · Archives of Medical Science · doi:10.5114/aoms.2019.83173 · Cited by 10
“the telomere – p53–PPARG (peroxisome proliferator-activated receptor g) axis, and also by the telomerase enzyme, but the exact mechanisms are still unknown [7, 48, 49].”
BackgroundGonzález‐Puertos, V. Y., Maciel-Barón, L. Á., Barajas-Gómez, B. A., López‐Díazguerrero, N. E., & Königsberg, M. (2015) · PubMed · Cited by 10
Guarding chromosomes from oxidative DNA damage to the very end
Tan, R., & Lan, L. (2016) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmw040 · Cited by 10
Cau, P., Navarro, C. L., Harhouri, K., Roll, P., Sigaudy, S., Kaspi, É., Perrin, S., Sandre‐Giovannoli, A. D., & Lévy, N. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.03.022 · Cited by 10
Watanuki, S., Kobayashi, H., Sugiura, Y., Yamamoto, M., Karigane, D., Shiroshita, K., Sorimachi, Y., Fujita, S., Morikawa, T., Koide, S., et al. (2023) · eLife · doi:10.7554/elife.87674 · Cited by 19
Hao, Y., Lv, M., Peng, J. P., Kuang, D., Zhang, Z., Zhang, Z., Wang, T., Yang, B., Wei, Z., Zhou, P., et al. (2023) · Molecular Medicine Reports · doi:10.3892/mmr.2023.13093 · Cited by 10
“‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ increased cellular reactive oxygen species levels (28).”
Figarola-Centurión, I., Escoto-Delgadillo, M., González-Enríquez, G. V., Gutiérrez-Sevilla, J. E., Vázquez-Valls, E., Cárdenas-Bedoya, J., & Torres-Mendoza, B. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417566 · Cited by 9
Telomerase is essential for cardiac differentiation and sustained metabolism of human cardiomyocytes
Chatterjee, S., Leach-Mehrwald, M., Huang, C.-K., Xiao, K., Fuchs, M., Otto, M., Lu, D., Dang, V., Winkler, T., Dunbar, C. E., et al. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05239-7 · Cited by 9
“Sahin et al. reported that telomere dysfunction is detrimental to mitochondrial metabolism via the telomere-p53-PGC axis, which ultimately disrupts cardiac function [13].”
Chik, H. Y. J., Mannarelli, M., dos Remedios, N., Simons, M. J. P., Burke, T. A., Schroeder, J., & Dugdale, H. L. (2024) · Molecular Ecology · doi:10.1111/mec.17455 · Cited by 13
“The accumulation of senescent cells could hinder tissue functions, lead to organ failure and eventual death (Barrett et al., 2013 ; Monaghan, 2010; Sahin et al., 2011 ).”
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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