Stress, cell senescence and organismal ageing
Open accessAbstract
Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely accepted that senescence plays a role in vivo. An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing. However, mostly due to a lack of availability of tissues and specific markers, less is known about the importance of cell senescence in humans. In this review, we summarize some of the key findings in the field of senescence, stress-induced senescence and telomeres. We focus particularly on the role of telomere dysfunction and senescence during the ageing process as well as potential interventions, including pharmacological approaches like telomerase activators and senolytics, to counteract their detrimental effects in ageing and disease.
AI snapshot
Written from the paper’s full text.
TL;DR
This review summarizes cellular senescence, stress-induced premature senescence (SIPS), and telomere dysfunction, arguing that senescence may contribute to organismal ageing while human evidence remains limited. It discusses senolytics and SASP-suppressing drugs as potential interventions and highlights unresolved questions about causality and senescent-cell burden in human tissues.
Key findings
- Replicative senescence in human fibroblasts is primarily driven by telomere shortening, and ectopic telomerase expression bypasses the senescence-induced arrest. SIPS can be induced by sublethal stress in 3–10 days with no or modest telomere shortening, but persistent telomeric DNA damage can occur independently of telomere length and telomerase, so some SIPS is telomere-dependent.
- In vivo, telomere shortening occurs in some tissues and shows weak correlations with donor age; comparative data across over 60 mammalian species indicate that smaller, short-lived species tend to have long telomeres and high telomerase, and telomere length is not a limiting factor for lifespan. A human study of over 4000 people over 10 years found no association between telomere length changes and mortality or morbidity.
- Senescent cells can be beneficial (tumour suppression, wound healing, embryonic development, insulin secretion) or detrimental via the SASP. Genetic clearance of senescent cells in mice delays age-related disorders, protects from cancer, and extends median but not maximum lifespan; senolytics such as dasatinib plus quercetin, ABT-263/ABT-737, and a FOXO4 peptide improve healthspan in mouse models.
- A major challenge is the absence of a universal senescence marker; SA-β-gal has false positives, and the exact frequency of senescent cells in older tissues and healthy humans remains unknown.
Methods
- Narrative review; no primary experiments or new data are reported.
- Synthesizes published literature on cellular senescence, telomeres, SIPS, in vivo mouse models, comparative biology, and pharmacological interventions.
- Main analysis is qualitative synthesis; no systematic search strategy, inclusion criteria, or meta-analysis is described.
Limitations
- Stated in paper: lack of human tissues and specific markers limits knowledge of senescence in humans; most in vivo evidence comes from laboratory mice, which have known limitations; the exact frequency of senescent cells in older tissues and healthy humans is unknown; causality of senescence in ageing remains debated; and in vivo rates of occurrence and turnover of senescent cells are poorly understood.
- Evident from text: as a narrative review, it does not systematically assess bias or quantify effect sizes, and many cited findings are from mouse models with uncertain translation to humans.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 43 cited sources checked · 0 supported · 0 flagged
- Premisenone given
An emerging body of evidence from animal models, particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing.
“An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing.”
Quote in the paperNot a substantial claim - Premisenone given
Senescence plays a role in vivo.
“It is also now widely accepted that senescence plays a role in vivo.”
Quote in the paperSubstantial claim - Premisecitation
During in vitro ageing, telomeres shorten gradually in each subcultivation.
“During in vitro ageing, the telomeres shorten gradually in each subcultivation (Harley et al., 1990).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Harley et al., 1990 source
Not checked in the free run.
- Premisecitation
Stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence (SIPS).
“Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS.”
Quote in the paperSubstantial claim - Premisecitation
With each cell division telomeres shorten progressively due to the end-replication problem.
“With each cell division telomeres shorten progressively, due to the so called “endreplication problem”.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites de Lange, 2005 source
Not checked in the free run.
- Premisecitation
Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts.
“Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts.”
- Also stated in: § 2. Of telomeres and senescence · boosted
“Telomere shortening is the primary cause of RS in human fibroblasts, since it has been shown that ectopic expression of telomerase, an enzyme able to counteract telomere shortening, is able to bypass the senescence-induced arrest (Bodnar et al., 1998).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bodnar et al., 1998 source
Not checked in the free run.
- Also stated in: § 2. Of telomeres and senescence · boosted
- Premisecitation
Telomere damage irrespective of length has also been observed with age in hippocampal neurons and in the liver of baboons.
“Telomere damage irrespectively of length has also been observed with age in hippocampal neurons and in the liver of baboons (Fumagalli et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Fumagalli et al., 2012 source
Not checked in the free run.
- Interpretationreasoning
If senescence plays a detrimental role during ageing in vivo, this may occur independently of telomere length.
“Altogether, these studies suggest that: 1) telomere length is not a limiting factor in an organism's lifespan, and 2) if senescence plays a detrimental role during ageing in vivo (discussed in the next section), this may occur independently of telomere length.”
Quote in the paperSubstantial claim - Premisecitation
During replicative senescence, fibroblasts accumulate proteins involved in the DNA damage response at telomeric regions, including γH2A.X, 53BP1, MDC1 and NBS1.
“Moreover, it was shown that during RS, fibroblasts accumulate proteins involved in the DDR at telomeric regions, including γH2A.X, 53BP1, MDC1 and NBS1 (d'Adda di Fagagna et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites d'Adda di Fagagna et al., 2003 source
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- Premisecitation
Telomere shortening precipitates the loss of shelterin components and destabilization of the t-loop conformation, resulting in exposure of the telomere end.
“It is thought that with each cell division, telomere shortening precipitates the loss of “shelterin” components and the destabilization of the t-loop conformation, resulting in exposure of the telomere end (Griffith et al., 1999).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Griffith et al., 1999 source
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- Premisecitation
Telomeric lesions occur irrespective of telomere length and the presence or absence of the enzyme telomerase.
“Interestingly, these telomeric lesions occur irrespectively of telomere length and the presence or absence of the enzyme telomerase (Fumagalli et al., 2012;Hewitt et al., 2012).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
In human cancer cells with elongated telomeres, cells with very long telomeres were more sensitive to ionising irradiation.
“In a study where telomeres were elongated in human cancer cells, it was shown that cells with very long telomeres were more sensitive to ionising irradiation (Fairlie and Harrington, 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Fairlie and Harrington, 2015
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- Premisecitation
Normal mice show an age-dependent increase in telomeric-associated DNA damage foci in the gut, liver and lung, which occurs independently of telomere length.
“Normal mice show an age-dependent increase in telomeric-associated DNA damage foci (TAF) in the gut, liver and lung of mice, which occurs independently of telomere length (Birch et al., 2015;Hewitt et al., 2012).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
Overall, telomere shortening may occur in some tissues in vivo in association with certain pathologies and with age.
“Overall, telomere shortening may occur in some tissues in vivo in association with certain pathologies and with age.”
Quote in the paperNot a substantial claim - Premisecitation
D+Q improves lung function in a mouse model of idiopathic pulmonary fibrosis.
“Moreover, D + Q administration was shown to improve vasomotor function in aged and hypercholesterolaemic mice (Roos et al., 2016), improve lung function in a mouse model of idiopathic pulmonary fibrosis (Schafer et al., 2017) and in mouse models of hepatic steatosis (Ogrodnik et al., 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Schafer et al., 2017 source
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- Premisecitation
In melanocytic nevi, telomeres signalling a DNA damage response were not shorter when compared to functional ones.
“In melanocytic nevi it was shown that telomeres signalling a DDR were not shorter when compared to functional ones (Suram et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Suram et al., 2012 source
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- Premisecitation
Exposure to different types of acute sub-lethal stresses such as oxidative stress and DNA damaging agents induces cellular senescence in different cell types at relatively short periods of time (3 to 10 days) without or with modest telomere shortening.
“Exposure to different types of acute sub-lethal stresses such as oxidative stress and DNA damaging agents was shown to induce cellular senescence in different cell types at relatively short periods of time (ranging from 3 to 10 days) without or with modest telomere shortening.”
Quote in the paperSubstantial claim - Premisecitation
Telomerase expression in normal human fibroblasts does not protect against SIPS.
“Work by Olivier Toussaint also showed that telomerase expression in normal human fibroblasts does not protect against SIPS, suggesting that mechanisms other than telomere shortening must cause the appearance of the senescence phenotype (de Magalhães et al., 2002).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites de Magalhães et al., 2002 source
Not checked in the free run.
- Premisecitation
Mouse-derived embryonic fibroblasts, which have long telomeres and express telomerase, undergo SIPS.
“Moreover, mouse-derived embryonic fibroblasts, which have long telomeres and express the enzyme telomerase, were shown to undergo SIPS (Parrinello et al., 2003).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Parrinello et al., 2003 source
Not checked in the free run.
- Premisecitation
In small airway epithelial cells in the lungs of COPD patients, which show increased senescence markers such as p16, damaged telomeres are not significantly shorter.
“Moreover, analysis of individual telomeres in small airway epithelial cells in the lungs of Chronic Obstructive Pulmonary Disease (COPD) patients, which show increased senescence markers such as p16, has also revealed that damaged telomeres are not significantly shorter (Birch et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Birch et al., 2015 source
Not checked in the free run.
- Premisecitation
D+Q administration improves vasomotor function in aged and hypercholesterolaemic mice.
“Moreover, D + Q administration was shown to improve vasomotor function in aged and hypercholesterolaemic mice (Roos et al., 2016), improve lung function in a mouse model of idiopathic pulmonary fibrosis (Schafer et al., 2017) and in mouse models of hepatic steatosis (Ogrodnik et al., 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Roos et al., 2016 source
Not checked in the free run.
- Interpretationreasoning
Telomere length is not a limiting factor in an organism's lifespan.
“Altogether, these studies suggest that: 1) telomere length is not a limiting factor in an organism's lifespan, and 2) if senescence plays a detrimental role during ageing in vivo (discussed in the next section), this may occur independently of telomere length.”
Quote in the paperSubstantial claim - Premisecitation
Depletion of shelterin components such as TRF2 or POT1 leads to activation of a DNA damage response at telomere ends.
“Consistent with this hypothesis, depletion of “shelterin” components such as TRF2 or POT1 leads to activation of a DNA damage response (DDR) at telomere ends (Takai et al., 2003;Wu et al., 2006).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Takai et al., 2003 source
Not checked in the free run.
- cites Wu et al., 2006
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- Interpretationreasoning
Because senescent cells can secrete pro-inflammatory cytokines and other factors that disrupt the tissue microenvironment, they may contribute to disruption of cell and tissue function.
“Because senescent cells can secrete pro-inflammatory cytokines and other factors that disrupt the tissue microenvironment, they may contribute to disruption of cell and tissue function.”
Quote in the paperSubstantial claim - Interpretationcitation
The evolution of large body sizes and longevity is strongly associated with the evolution of short telomeres and telomerase suppression, presumably for tumour suppression.
“Taken together, it seems that the evolution of large body sizes and longevity is strongly associated with the evolution of short telomeres and telomerase suppression, presumably for tumour suppression (de Magalhaes, 2013; Gomes et al., 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
D+Q improves in mouse models of hepatic steatosis.
“Moreover, D + Q administration was shown to improve vasomotor function in aged and hypercholesterolaemic mice (Roos et al., 2016), improve lung function in a mouse model of idiopathic pulmonary fibrosis (Schafer et al., 2017) and in mouse models of hepatic steatosis (Ogrodnik et al., 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ogrodnik et al., 2017 source
Not checked in the free run.
- Premisecitation
Several drugs have been shown to eliminate senescent cells in vivo and have beneficial effects in models of ageing and age-related disease.
“Several drugs have been shown to eliminate senescent cells in vivo and have beneficial effects in models of ageing and age-related disease.”
Quote in the paperSubstantial claim - Interpretationcitation
These landmark studies provide evidence that senescent cells can promote age-related phenotypes, at least in a subset of organs.
“Therefore, these landmark studies provide evidence that senescent cells can promote age-related phenotypes, at least in a subset of organs.”
Quote in the paperSubstantial claim - Premisecitation
Inhibition of NF-κB signalling both genetically and pharmacologically prevents age-related deterioration in progeroid mouse models.
“Inhibition of NF-κB signalling (the main transcription factor regulating the SASP) both genetically and pharmacologically, has been shown to prevent age-related deterioration in progeroid mouse models (Osorio et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Osorio et al., 2012 source
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- Premisecitation
The increase in knowledge about senescence in vivo is mostly through work using laboratory mice.
“this is mostly through work using laboratory mice”
Quote in the paperSubstantial claim0 of 1 sources checked- cites de Magalhaes, 2014 source
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- Interpretationcitation
Even a small fraction of senescent cells in organs may decrease organ function.
“Even a small fraction of senescent cells in organs may impair tissue renewal and homeostasis, decrease organ function, and contribute to the ageing phenotype, as shown by the studies genetically ablating senescent cells.”
Quote in the paperSubstantial claim - Interpretationnone given
There is little evidence that cells running out of divisions are a major factor in ageing.
“While there is little evidence to suggest that cells running out of divisions are a major factor in ageing”
Quote in the paperNot a substantial claim - Interpretationcitation
Even a small fraction of senescent cells in organs may contribute to the ageing phenotype.
“Even a small fraction of senescent cells in organs may impair tissue renewal and homeostasis, decrease organ function, and contribute to the ageing phenotype, as shown by the studies genetically ablating senescent cells.”
Quote in the paperSubstantial claim - Premisecitation
Laboratory mice have known limitations.
“which have known limitations (de Magalhaes, 2014)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites de Magalhaes, 2014 source
Not checked in the free run.
- Interpretationcitation
Even a small fraction of senescent cells in organs may impair tissue renewal and homeostasis.
“Even a small fraction of senescent cells in organs may impair tissue renewal and homeostasis, decrease organ function, and contribute to the ageing phenotype, as shown by the studies genetically ablating senescent cells.”
Quote in the paperSubstantial claim
- May combine two claims. 14
- Classified as probably not a substantial claim. 5
May combine two claims.
PremisecitationAs the senescent phenotype develops, most DNA damage is repaired within 24 h; however, damage at telomeric regions remains unrepaired for months, contributing to a persistent and unresolved DNA damage response.
“As the senescent phenotype develops, most of the DNA damage is repaired within 24 h; however, damage at telomeric regions remains unrepaired for months, contributing to a persistent and unresolved DNA damage response (Hewitt et al., 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hewitt et al., 2012 source
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May combine two claims.
PremisecitationInhibition of the JAK pathway (using ruxolitinib) suppresses the SASP and alleviates age-related tissue dysfunction.
“Inhibition of the JAK pathway (using the drug ruxolitinib) has been shown to suppress the SASP and alleviate age-related tissue dysfunction (Xu et al., 2015).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Xu et al., 2015
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May combine two claims.
PremisecitationInduction of SIPS is characterized initially by DNA damage that occurs randomly all over the genome, and subsequent activation of a DNA damage response.
“Induction of SIPS is characterized initially by DNA damage, which occurs randomly all over the genome, and subsequent activation of a DDR.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Hewitt et al., 2012 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThere may be different types of senescence rather than a universal phenotype.
“Given the multitude of functions of senescent cells, which can be of a positive or negative nature depending on the context, it has been argued that there may be different types of senescence rather than a universal phenotype.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationnone givenSenescent cells likely accumulate in some tissues and may contribute to organ dysfunction, yet whether they are causal factors in ageing remains a subject of debate.
“As mentioned above, senescent cells likely accumulate in some tissues and may contribute to organ dysfunction, yet whether they are causal factors in ageing remains a subject of debate.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningWhile results on telomere length and mortality support the idea that telomere shortening is a marker of stress and age-related pathology, they do not prove that telomere shortening is a causal factor in ageing.
“While these results support the idea that telomere shortening is a marker of stress and age-related pathology, they do not prove that telomere shortening is a causal factor in ageing.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationGenetic elimination of p16-positive senescent cells ameliorated atherosclerosis and osteoarthritis in mice.
“Further highlighting the potential of targeting senescence as a way to counteract age-related diseases, recent work in mice has shown that genetic elimination of p16-positive senescent cells ameliorated atherosclerosis (Childs et al., 2016) and osteoarthritis (Jeon et al., 2017).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationDasatinib and quercetin (D+Q) when given in combination reduce senescent cells in aged, radiation-exposed and progeroid mice, improving several healthspan parameters.
“Dasatinib and quercetin (D + Q) when given in combination have been shown to reduce senescent cells in aged, radiation-exposed and progeroid mice, improving several healthspan parameters (Zhu et al., 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zhu et al., 2015 source
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May combine two claims.
PremisecitationA FOXO4 peptide that perturbs the FOXO4 interaction with p53 clears senescent cells and improves healthspan in aged and progeroid mice.
“Recently, a FOXO4 peptide that perturbs the FOXO4 interaction with p53 was shown to clear senescent cells and improve healthspan in aged and progeroid mice (Baar et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Baar et al., 2017 source
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May combine two claims.
PremisecitationApart from cell-cycle arrest, senescent cells experience dramatic changes in gene expression, metabolism, epigenome, and have a distinct secretome profile known as the Senescence-Associated Secretory Phenotype (SASP).
“Apart from cell-cycle arrest, senescent cells have been shown to experience dramatic changes in terms of gene expression, metabolism, epigenome and, importantly, have a distinct secretome profile, known as the Senescence-Associated Secretory Phenotype (SASP) (Coppé et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Coppé et al., 2008 source
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May combine two claims.
InterpretationreasoningWhile SIPS induced by sub-lethal acute stress is not driven by the shortening of telomeres per se, in some circumstances SIPS can still be classified as a telomere-dependent process.
“Thus, while SIPS induced by sub-lethal acute stress is not driven by the shortening of telomeres per se, in some circumstances SIPS can still be classified as a telomere-dependent process.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationDNA damage response activation can result in activation of transcription factor p53, leading to expression of p21, which together with activation of p16 are thought to be the major pathways in the induction of senescence.
“DDR activation can result in the activation of transcription factor p53 which is involved in a variety of processes including DNA repair and apoptosis, but most notably results in expression of cyclindependent kinase inhibitor p21, which together with activation of p16, are thought to be the major pathways in the induction of senescence (Beauséjour et al., 2003).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Beauséjour et al., 2003 source
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May combine two claims.
PremisecitationInhibitors of the BCL-2 family, such as ABT-263 and ABT-737, reduce senescent hematopoietic and muscle stem cells in radiation-exposed and aged mice and senescent cells in the lung and epidermis.
“Inhibitors of the BCL-2 family, such as ABT-263 (navitoclax) and ABT-737, have been shown to reduce senescent hematopoietic and muscle stem cells in radiation-exposed and aged mice (Chang et al., 2016) and senescent cells in the lung and epidermis (Yosef et al., 2016).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationA chronic SASP is able to induce senescence in adjacent young cells, contributing to tissue dysfunction and paradoxically tumorigenesis.
“It has been shown that a “chronic” SASP is able to induce senescence in adjacent young cells, contributing to tissue dysfunction (Acosta et al., 2013;Jurk et al., 2014) and paradoxically tumorigenesis (Krtolica et al., 2001).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationInhibition of the mTOR pathway (using rapamycin), which extends lifespan in a variety of model organisms, is an effective SASP suppressor.
“For instance, inhibition of the mTOR pathway (using the drug rapamycin), which has been shown to extend lifespan in a variety of model organisms (de Magalhaes et al., 2012;Harrison et al., 2009), is an effective SASP suppressor (Correia-Melo et al., 2016;Herranz et al., 2015;Laberge et al., 2015).”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningGiven that the SASP is required in certain physiological contexts, it is still unclear whether targeting the SASP would be a viable anti-ageing therapy.
“However, given the fact that the SASP is required in certain physiological contexts, it is still unclear whether targeting the SASP would be a viable anti-ageing therapy.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenWe still know very little about in vivo rates of occurrence and turnover of senescent cells.
“Finally, we still know very little about in vivo rates of occurrence and turnover of senescent cells.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOur knowledge about senescence in vivo has increased exponentially in the last decade.
“While our knowledge about senescence in vivo has increased exponentially in the last decade”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites de Magalhaes, 2014 source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone givenStress and various insults are possible contributors to senescence in vivo.
“it is possible that stress and various insults are contributors to senescence in vivo.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Findings from mouse models of senescence and ageing are informative about human ageing.
“In this review, we summarize some of the key findings in the field of senescence, stress-induced senescence and telomeres.We focus particularly on the role of telomere dysfunction and senescence during the ageing process as well as potential interventions, including pharmacological approaches like telomerase activators and senolytics, to counteract their detrimental effects in ageing and disease.”
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?
Senotherapeutic drugs could potentially treat a variety of conditions primarily or secondarily mediated by senescent cell accumulation.
“The use of senotherapeutic drugs could potentially be effective in treating a variety of conditions primarily or secondarily mediated by accumulation of senescent cells [6, 33, 67–87].”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Conflicting conclusions about telomere length and species longevity
MinorThe paper first says there is no connection between mean telomere length and mammalian species longevity, but later concludes that longevity is strongly associated with the evolution of short telomeres.
“In terms of comparative biology, no connection appears to exist between the mean telomere length of cells and the longevity of mammalian species.”
“Taken together, it seems that the evolution of large body sizes and longevity is strongly associated with the evolution of short telomeres and telomerase suppression, presumably for tumour suppression (de Magalhaes, 2013; Gomes et al., 2011).”
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InfluentialExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
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A DNA damage checkpoint response in telomere-initiated senescence
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- Authors
- de Magalhães, J. P., & Passos, J. F.
- Affiliations
- Newcastle University (GB)
- ORCID
- Passos, João F.
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 170
- Pages
- 2-9
- ISSN
- 0047-6374 (ISSN-L)
- OpenAlex
- W2733273049
- Cited by
- 316
- References
- 122
- Citations by year
- 2026: 17 · 2025: 37 · 2024: 28 · 2023: 31 · 2022: 43 · 2021: 44 · 2020: 55 · 2019: 40 · 2018: 17 · 2017: 3
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Mechanisms of Ageing and Development (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Wellcome Trust (104978, 104978/Z/14/Z, RPG-2016-015)
- Methuselah Foundation
- Leverhulme Trust (RPG‐2016‐015)
- Medical Research Council (MR/L016354/1)
- Biotechnology and Biological Sciences Research Council (BB/K017314/1, BB/H022384/1)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, stress-induced premature senescence, telomere shortening, telomere dysfunction, replicative senescence, senolytics, telomerase activators, tumor suppression, wound healing, embryonic development
- MeSH terms
- Aging, Humans, Neoplasms, Stress, Physiological, Wound Healing, Cellular Senescence, Embryonic Development, Telomere Homeostasis
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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