Stress, cell senescence and organismal ageing

In the paper

“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.”

In the paper

“It is also now widely accepted that senescence plays a role in vivo.”

In the paper

“During in vitro ageing, the telomeres shorten gradually in each subcultivation (Harley et al., 1990).”

What the sources say

• Not checked yetcites Harley et al., 1990 source

In the paper

“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.”

In the paper

“With each cell division telomeres shorten progressively, due to the so called “endreplication problem”.”

What the sources say

• Not checked yetcites de Lange, 2005 source

In the paper

“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).”

What the sources say

• Not checked yetcites Bodnar et al., 1998 source

In the paper

“Telomere damage irrespectively of length has also been observed with age in hippocampal neurons and in the liver of baboons (Fumagalli et al., 2012).”

What the sources say

• Not checked yetcites Fumagalli et al., 2012 source

In the paper

“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.”

In the paper

“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).”

What the sources say

• Not checked yetcites d'Adda di Fagagna et al., 2003 source

In the paper

“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).”

What the sources say

• Not checked yetcites Griffith et al., 1999 source

In the paper

“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).”

What the sources say

• Not checked yetcites Fumagalli et al., 2012 source
• Not checked yetcites Hewitt et al., 2012 source

In the paper

“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).”

What the sources say

• Not checked yetcites Fairlie and Harrington, 2015

In the paper

“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).”

What the sources say

• Not checked yetcites Birch et al., 2015 source
• Not checked yetcites Hewitt et al., 2012 source

In the paper

“Overall, telomere shortening may occur in some tissues in vivo in association with certain pathologies and with age.”

In the paper

“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).”

What the sources say

• Not checked yetcites Schafer et al., 2017 source

In the paper

“In melanocytic nevi it was shown that telomeres signalling a DDR were not shorter when compared to functional ones (Suram et al., 2012).”

What the sources say

• Not checked yetcites Suram et al., 2012 source

In the paper

“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.”

In the paper

“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).”

What the sources say

• Not checked yetcites de Magalhães et al., 2002 source

In the paper

“Moreover, mouse-derived embryonic fibroblasts, which have long telomeres and express the enzyme telomerase, were shown to undergo SIPS (Parrinello et al., 2003).”

What the sources say

• Not checked yetcites Parrinello et al., 2003 source

In the paper

“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).”

What the sources say

• Not checked yetcites Birch et al., 2015 source

In the paper

“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).”

What the sources say

• Not checked yetcites Roos et al., 2016 source

In the paper

“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.”

In the paper

“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).”

What the sources say

• Not checked yetcites Takai et al., 2003 source
• Not checked yetcites Wu et al., 2006

In the paper

“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.”

In the paper

“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).”

What the sources say

• Not checked yetcites de Magalhaes, 2013 source
• Not checked yetcites Gomes et al., 2011 source

In the paper

“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).”

What the sources say

• Not checked yetcites Ogrodnik et al., 2017 source

In the paper

“Several drugs have been shown to eliminate senescent cells in vivo and have beneficial effects in models of ageing and age-related disease.”

In the paper

“Therefore, these landmark studies provide evidence that senescent cells can promote age-related phenotypes, at least in a subset of organs.”

In the paper

“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).”

What the sources say

• Not checked yetcites Osorio et al., 2012 source

In the paper

“this is mostly through work using laboratory mice”

What the sources say

• Not checked yetcites de Magalhaes, 2014 source

In the paper

“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.”

In the paper

“While there is little evidence to suggest that cells running out of divisions are a major factor in ageing”

In the paper

“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.”

In the paper

“which have known limitations (de Magalhaes, 2014)”

What the sources say

• Not checked yetcites de Magalhaes, 2014 source

In the paper

“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.”