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DNA Repair, Genome Stability, and Aging
Open accessAbstract
Aging can be defined as progressive functional decline and increasing mortality over time. Here, we review evidence linking aging to nuclear DNA lesions: DNA damage accumulates with age, and DNA repair defects can cause phenotypes resembling premature aging. We discuss how cellular DNA damage responses may contribute to manifestations of aging. We review Sir2, a factor linking genomic stability, metabolism, and aging. We conclude with a general discussion of the role of mutant mice in aging research and avenues for future investigation.
Checked 2026-10-06 · 29 references not checked yet
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Written from the paper’s full text.
TL;DR
This review argues that nuclear DNA damage accumulates with age and that defects in DNA repair produce premature-aging phenotypes in mice and humans, with p53-mediated senescence and apoptosis as a shared downstream mechanism. It also reviews Sir2/SIRT1 as a link between genome stability, metabolism, and life span.
Key findings
- DNA damage and mutations accumulate with age in mammals; cytogenetically visible lesions (translocations, insertions, dicentrics, acentric fragments) increase in aging cells, and mutation spectra vary considerably between tissues.
- Many premature-aging syndromes arise from mutations in DNA repair genes: ATM (Ataxia-Telangiectasia), CSA/CSB (Cockayne syndrome), XPD (trichothiodystrophy), WRN (Werner syndrome), plus mouse hypomorphs in Rad50 and BRCA1 and NHEJ mutants (Ku80, DNA-PKcs).
- Aging-like phenotypes in Rad50s/s, BRCA1Δ11/Δ11/p53+/−, and several NHEJ mutants are largely p53-dependent responses to unrepaired damage rather than direct consequences of the lesions; p53 deficiency rescues premature senescence and neuronal apoptosis but not small size.
- Sir2 links genome stability, metabolism, and life span: loss of Sir2 increases rDNA recombination and shortens yeast life span, while an extra copy extends it; overexpression or pharmacologic activation of Sir2 extends life span in worms and flies.
Methods
- Narrative review, not primary research. The authors synthesize evidence from yeast, C. elegans, Drosophila, mouse models, and human progeroid syndromes.
- Focus is on nuclear (not mitochondrial) DNA damage in mammalian aging, emphasizing recent mouse models; mitochondrial ROS is deferred to the companion Balaban et al. review in the same issue.
- Key evidence discussed includes mouse DNA repair/metabolism mutants with aging features (Table 1), features of normal aging in wild-type mice (Table 2), and pathway diagrams for DSB repair (NHEJ, HR) and NER.
Limitations
- Stated: the evidence that cellular senescence plays a role in aging is correlative, and "a causal relationship between cellular senescence and organismal aging has yet to be proved."
- Stated: premature aging models are "segmental progerias" that reproduce only some aspects of aging, and the histopathology of normal aging corresponds poorly with changes in these models; genetic background, housing, infection, and diet likely modify phenotypes.
- Stated: it is unclear why only certain DNA repair mutants in particular pathways show progeroid phenotypes, and many implicated factors have roles beyond DNA repair; measurement of ROS and oxidative damage is experimentally difficult, with discrepant estimates of oxidatively damaged DNA.
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Claims the paper makes
135 Not checked yet · 46 Own interpretation · 11 No basis given · 1 Sources not found
In the paper
“Such uncapped telomeres are then recognized by the cell cycle checkpoint machinery as DNA damage, leading to cell cycle arrest (Ben-Porath and Weinberg, 2004”
What the sources say
- Not checked yetcites Ben-Porath and Weinberg, 2004 source
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In the paper
“Caloric restriction, an intervention that extends life span in many organisms, likely decreases ROS production (Barja, 2004”
What the sources say
- Not checked yetcites Barja, 2004 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In many primary human cell lines, replicative senescence occurs secondary to attrition of the ends of the chromosomes, the telomeres, in a process termed “intrinsic senescence” (Itahana et al., 2004”
What the sources say
- Not checked yetcites Itahana et al., 2004 source
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In the paper
“many mutations in DNA repair genes that cause premature aging phenotypes also confer premature replicative senescence (Table 1).”
What the sources say
- Not checked yetcites Table 1
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In the paper
“Such analyses have revealed considerable variation in mutation spectra between different tissues.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In model organisms, many mutations that promote longevity concomitantly increase oxidative stress resistance (Finkel and Holbrook, 2000”
What the sources say
- Not checked yetcites Finkel and Holbrook, 2000
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Terc deficiency in mice leads to progressive telomere attrition in successive mouse generations”
What the sources say
- Not checked yetcites Espejel and Blasco, 2002
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This highlights the difficulty of accurately measuring ROS and oxidative damage experimentally.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Of note, late-generation Terc-deficient mice show some signs of accelerated aging (Lee et al., 1998; Rudolph et al., 1999”
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Critically short telomeres trigger the onset of senescence through a process that may involve loss of the t loop structure and/or loss of protective proteins (referred to as “uncapping”).”
What the sources say
- Not checked yetcites Ben-Porath and Weinberg, 2004 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- It may state two separate claims as one. 54
- Probably not a substantial claim. 22
- The quote only partly states this claim. 1
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Phosphorylation of p53 by ATM and kinases downstream of ATM is a major mechanism leading to upregulation of p53 levels and activity, although p53 also can be activated via ATM-independent mechanisms.”
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Replicative life span of human cells is altered by culture under different oxygen tensions”
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“p53, through modulation of various downstream targets, triggers arrest/senescence or apoptosis (Meek, 2004”
What the sources say
- Not checked yetcites Meek, 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As normal byproducts of metabolism, ROS are a potential source of chronic, persistent DNA damage in all cells and may contribute to aging (Sohal and Weindruch, 1996”
What the sources say
- Not checked yetcites Sohal and Weindruch, 1996
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The initial step in DSB repair is detection of the lesion, and this step involves the ataxia-telangiectasia mutated (ATM) kinase, other related phosphatidylinositol 3-kinase-like kinases (PIKKs), and other proteins (Figure 2; Bassing and Alt, 2004”
What the sources say
- Not checked yetcites Bassing and Alt, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“MEFs derived from M. musculus possess long telomeres and easily detectable telomerase activity (Itahana et al., 2004”
What the sources say
- Not checked yetcites Itahana et al., 2004 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The G strand overhang is the substrate for the enzyme telomerase, which employs an RNA template, Terc, to extend telomeres during S phase, thereby countering the natural shortening of telomeres that would otherwise occur with each cell division.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Activated ATM phosphorylates numerous proteins involved in the G1/S, intra-S, and G2/M checkpoint responses and additionally phosphorylates factors involved in DNA repair (Bassing and Alt, 2004”
What the sources say
- Not checked yetcites Bassing and Alt, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In mammalian cells, the ends of the chromosomes consist of a terminal 3′ single-stranded tail, the G strand overhang, which is buried into adjacent double-stranded repetitive telomeric DNA, forming a protective “t loop” higher-order structure (de Lange, 2002”
What the sources say
- Not checked yetcites de Lange, 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“which found that many nuclear genes involved in critical neural functions show reduced expression after age 40, concomitant with elevated levels of oxo8dG and DNA damage in their promoters.”
What the sources say
- Not checked yetcites Lu et al., 2004
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Activated p53 stimulates or represses transcription of many target genes and coordinates checkpoint, senescence, and apoptosis pathways in response to DSBs and other signals.”
What the sources say
- Not checked yetcites Meek, 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, senescent stromal cells can actually promote the growth of epithelial cancers, malignancies that occur with increased incidence in the elderly.”
What the sources say
- Not checked yetcites Krtolica and Campisi, 2002
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Unrepaired or improperly repaired DSBs have serious potential consequences for the cell: cell death, senescence, dysregulation of cellular functions, genomic instability, and, in higher organisms, oncogenic transformation.”
What the sources say
- Not checked yetcites Bassing and Alt, 2004
plainconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“senescent cells accumulate in vivo in mammals with increasing age and at sites of pathology (Itahana et al., 2004”
What the sources say
- Not checked yetcites Itahana et al., 2004 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In brief, longer-lived species generally show higher cellular oxidative stress resistance and lower levels of mitochondrial ROS production than shorter-lived species.”
What the sources say
- Not checked yetcites Balaban et al., 2005 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“DNA damage accumulates with age”
- Also stated in: § Introduction · boosted
“A large body of evidence argues that DNA damage and mutations accumulate with age in mammals (Vijg, 2000”
What the sources say
- Not checked yetcites Vijg, 2000 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Introduction · boosted
In the paper
“a strain of DNA-PKcs-deficient mice recently has been noted to exhibit age-related pathologies, with osteopenia, intestinal atrophy, thymic lymphoma, and reduced longevity (Espejel et al., 2004b”
What the sources say
- Not checked yetcites Espejel et al., 2004b
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Mouse models of accelerated aging phenotypes are informative about normal aging processes.
In the paper
“a finding that might reflect different background mutations and/or housing conditions and the types of pathogens present (Petiniot et al., 2002”
What the sources say
- Not checked yetcites Petiniot et al., 2002 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Finally, ATM plays an important role in telomere maintenance; AT cells show shortened telomeres and an increased incidence of telomeric fusions (Pandita, 2002”
What the sources say
- Not checked yetcites Pandita, 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“mice deficient for these four factors are very small and show widespread neuronal apoptosis during embryogenesis”
What the sources say
- Not checked yetcites Ferguson and Alt, 2001
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NHEJ plays a critical role in general DNA DSB repair and, correspondingly, in the maintenance of genomic stability.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In particular, such cells manifest sensitivity to DSB-inducing agents and have marked genomic instability; they also grow poorly and senesce prematurely in culture (Barzilai et al., 2002”
What the sources say
- Not checked yetcites Barzilai et al., 2002 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Premature senescence and neuronal apoptosis, but not small size, are relieved by p53 deficiency.”
What the sources say
- Not checked yetcites Ferguson and Alt, 2001
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations raise the possibility that other aspects of the ATM-deficient phenotype, including the premature aging observed in human patients, may be influenced by environment.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Patients with mutations in the ATM gene suffer from Ataxia-Telangiectasia (AT), a condition characterized by a prematurely aged (progeroid) appearance, immunodeficiency, cerebellar degeneration, and cancer (Shiloh and Kastan, 2001”
What the sources say
- Not checked yetcites Shiloh and Kastan, 2001
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“a null mutation in a gene functioning downstream of p53 in the induction of apoptosis, p66Shc, confers oxidative stress resistance and extends mouse life span (Migliaccio et al., 1999”
What the sources say
- Not checked yetcites Migliaccio et al., 1999 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Rests on an assumption: Mouse models of accelerated aging phenotypes are informative about normal aging processes.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, NHEJ plays crucial roles in general and site-specific DSB repair, in telomere maintenance, and in maintenance of genomic stability.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“NHEJ is one of the two major DSB repair pathways in mammalian cells (Bassing and Alt, 2004”
What the sources say
- Not checked yetcites Bassing and Alt, 2004
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Persistently elevated ROS levels in AT cells might cause chronic damage to DNA and other cellular macromolecules.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Another potential function for ATM in suppressing progeroid phenotypes may be related to reported ATM functions in regulating intracellular ROS levels and sensitivity to these molecules (Barzilai et al., 2002; Ito et al., 2004”
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at the same time it promotes cellular senescence and apoptosis in response to DNA damage, potentially contributing to the clinical changes of aging.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“ATM deficiency in mice recapitulates many of these phenotypes, although the progeroid features of the mouse models are less prominent than in the human disease.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, mice lacking both ATM and Terc have higher levels of telomeric dysfunction than generation-matched Terc-deficient mutants, as well as proliferative defects in multiple tissues, decreased survival, and clinical evidence of premature aging (Wong et al., 2003”
What the sources say
- Not checked yetcites Wong et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, two mouse strains that express C-terminal p53 fragments along with full-length p53 have been reported to show accelerated aging phenotypes and a lower incidence of malignancy (Maier et al., 2004; Tyner et al., 2002”
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Mouse models of accelerated aging phenotypes are informative about normal aging processes.
In the paper
“BRCA1Δ11/Δ11 MEFs show increased chromosomal abnormalities and premature cellular senescence, and BRCA1Δ11/Δ11 embryos show tissue SA-β-galactosidase activity, a marker of senescence.”
What the sources say
- Not checked yetcites Cao et al., 2003b
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“although only cerebellar defects have been described in detail in these animals (Murai et al., 2001”
What the sources say
- Not checked yetcites Murai et al., 2001 source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Additionally, these XPDTTD mice show aging-associated changes such as wasting, scoliosis, osteoporosis, and melanocyte loss (de Boer et al., 2002”
What the sources say
- Not checked yetcites de Boer et al., 2002 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“NER can be subdivided into two pathways, global genome NER (GG-NER) and transcription-coupled NER (TC-NER), which differ with respect to the lesion detected and some of the factors involved (Mitchell et al., 2003; Figure 5”
What the sources say
- Not checked yetcites Mitchell et al., 2003 source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“mice homozygous for a BRCA1 hypomorphic allele and haploinsufficient for p53 (BRCA1Δ11/Δ11/p53+/−) are viable and have many features reminiscent of accelerated aging: wasting, skin atrophy, osteopenia, and malignancy (Cao et al., 2003b”
What the sources say
- Not checked yetcites Cao et al., 2003b
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Rests on an assumption: Mouse models of accelerated aging phenotypes are informative about normal aging processes.
In the paper
“cells deficient in Ligase IV and ATM or Terc and ATM show high levels of genomic instability and very rapid senescence (Sekiguchi et al., 2001; Wong et al., 2003”
What the sources say
- Not matchedcites Sekiguchi et al., 2001; Wong et al., 2003
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“homozygosity for a Rad50 hypomorphic allele (Rad50s/s) permits viability; Rad50s/s mice show a shortened life span, cancer predisposition, and hematopoietic stem cell and spermatogenic failure (Bender et al., 2002”
What the sources say
- Not checked yetcites Bender et al., 2002 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Mouse models of accelerated aging phenotypes are informative about normal aging processes.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Current findings suggest, however, that aging phenotypes likely do not result from a failure of DSB repair alone but instead from a loss of other functions or combinations of functions of these proteins, perhaps in concert with environmental factors, such as housing conditions and/or infection and/or background mutations.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Alternatively, the involvement of XPD and the CSB proteins in transcription suggests that impaired transcription of critical genes may play a role in causing these progeroid phenotypes, perhaps interacting with the repair defects in a complicated fashion.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“WS patients develop premature graying, cataract, loss of subcutaneous fat, skin atrophy, osteoporosis, diabetes, atherosclerosis, and malignancies.”
What the sources say
- Not checked yetcites Goto, 1997 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Defects in Rad50 or BRCA1 cause progeroid phenotypes.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Mouse models of accelerated aging phenotypes are informative about normal aging processes.
In the paper
“mutations in genes involved in this pathway do not produce aging manifestations: they are either lethal or confer no obvious phenotypes (Hasty et al., 2003”
What the sources say
- Not checked yetcites Hasty et al., 2003 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such complexities also may likely apply to other DNA repair proteins implicated in the suppression of aging as well”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“Defects in the TC-NER-specific factors CSA or CSB lead to Cockayne syndrome in humans, a severely debilitating disorder with striking progeroid features.”
What the sources say
- Not checked yetcites Mitchell et al., 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Deficiency of Mre11, Nbs1, or Rad50 is not compatible with cellular survival (Stracker et al., 2004”
What the sources say
- Not checked yetcites Stracker et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“degenerative changes in these models occur in both highly proliferative (intestine and skin) and relatively less proliferative (bone and liver) tissues, apparently sparing many other tissues of both types.”
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“leading to tissue attrition and aging.”
plaindirect- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
In the paper
“Additionally, SIRT1, like Sir2, has recently been shown to directly modify chromatin and silence transcription (Vaquero et al., 2004”
What the sources say
- Not checked yetcites Vaquero et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“it was proposed that WRN-deficient mice may not demonstrate a strong phenotype due to the abundant mouse telomere reserve (Lombard et al., 2000”
What the sources say
- Not checked yetcites Lombard et al., 2000 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, as discussed above, environmental factors including housing conditions, infectious agents, diet, and many other influences, also likely play a significant role in the expression of aging phenotypes in mouse models and, perhaps, in humans as well.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“to suppress recombination and turns off transcription at multiple genomic loci (Blander and Guarente, 2004”
What the sources say
- Not checked yetcites Blander and Guarente, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The role of SIRT1 in mammalian longevity has not yet been directly tested, since on a pure strain background SIRT1-deficient animals die very early as a consequence of multiple developmental defects (Cheng et al., 2003; McBurney et al., 2003”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Loss of Sir2 increases rDNA recombination and shortens life span; whereas an extra genomic copy of Sir2, which increases rDNA stability, extends life span (Kaeberlein et al., 1999”
What the sources say
- Not checked yetcites Kaeberlein et al., 1999 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, the phenotype of the WRN/Terc double knockout mouse argues that defective telomere maintenance is an important factor in producing the premature aging-like aspects of WS in humans, although it does not exclude a role for other functions of WRN at nontelomeric sites.”
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Also, it must be remembered that many of the DNA repair genes and factors implicated in suppressing aging also play roles in cellular processes other than DNA repair, and therefore aging-like phenotypes might be enhanced by impairment of other cellular functions in conjunction with altered DNA repair.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“This metabolic switch alters the metabolism of the cell, increasing the NAD/NADH ratio and/or decreasing levels of the Sir2 inhibitor nicotinamide, in turn activating Sir2 and increasing rDNA stability (reviewed in Blander and Guarente, [2004]”
What the sources say
- Not checked yetcites Blander and Guarente, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“SIRT1 possesses a large and growing list of targets, some of which, including p53 and forkhead transcription factors (mammalian homologs of Daf-16), modulate cellular resistance to oxidative and genotoxic stress (Blander and Guarente, 2004”
What the sources say
- Not checked yetcites Blander and Guarente, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Sir2 family members may play a general role in mediating caloric restriction (Sohal and Weindruch, 1996”
What the sources say
- Not checked yetcites Sohal and Weindruch, 1996
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“WRN also interacts with the telomeric protein TRF2 and can unwind and degrade telomeric D loop structures.”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Loss of Sir2 increases rDNA recombination and shortens life span; whereas an extra genomic copy of Sir2, which increases rDNA stability, extends life span (Kaeberlein et al., 1999”
What the sources say
- Not checked yetcites Kaeberlein et al., 1999 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It has been proposed that Sir2 activity ties the energy status of the yeast cell to longevity (Blander and Guarente, 2004; Lin et al., 2000”
What the sources say
- Not checked yetcites Blander and Guarente, 2004
- Not checked yetcites Lin et al., 2000 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Phenotypes ordinarily seen in late-generation Terc-deficient animals also occur earlier in the compound mutants and are associated with a greater degree of telomeric dysfunction.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“In mammals, there are seven Sir2 family members, designated SIRT1–SIRT7 (Frye, 2000”
What the sources say
- Not checked yetcites Frye, 2000 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“although in yeast the involvement of Sir2 in CR appears to be strain specific (Kaeberlein et al., 2004”
What the sources say
- Not checked yetcites Kaeberlein et al., 2004 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Aging encompasses a wide spectrum of degenerative processes, many of which are quite nonspecific, both clinically and pathologically (Harrison, 1994”
What the sources say
- Not checked yetcites Harrison, 1994 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mammalian aging is not likely a single process but rather the decline of many somatic functions, heavily influenced by the environment; this is a complex interplay that is extremely difficult to model accurately.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A related difficulty is that premature aging models fail to recapitulate all aspects of aging but are instead “segmental progerias” (Hasty and Vijg, 2004; Miller, 2004”
What the sources say
- Not checked yetcites Hasty and Vijg, 2004
- Not checked yetcites Miller, 2004 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For these reasons, genetic models of extended life span are likely to be more informative than models with reduced longevity with respect to physiologically relevant causes of decline and mortality; in such long-lived organisms, life span-limiting factors must of necessity be counteracted.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In models of premature aging, the most vulnerable system fails first, leading to death and precluding gain of insights from effects on other, potentially more relevant, organ systems.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“All mouse models that link DNA repair to aging possess defects in DNA repair and have shortened life spans.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper relies on this without support.
The induction of senescence depends on pathways involving the p53 and Rb proteins.
“The induction of senescence depends on pathways involving the p53 and Rb proteins (Figure 1).”
The paper relies on this without support.
The accurate maintenance of nuclear DNA is critical to cellular and organismal function.
“The accurate maintenance of nuclear DNA is critical to cellular and organismal function, and therefore, numerous DNA repair systems have evolved.”
The paper relies on this without support.
p53 suppresses the onset of malignancy and thereby extends life span.
“While p53 suppresses the onset of malignancy and thereby extends life span”
The paper relies on this without support.
The role of p53 in aging cannot be directly tested using p53-deficient mice because they die of malignancy before age-related changes become manifest.
“The role of p53 in aging cannot be directly tested using p53-deficient mice, as such animals invariably die of malignancy before age-related changes become manifest.”
The paper relies on this without support.
Mouse models of accelerated aging phenotypes are informative about normal aging processes.
“phenotypes resembling accelerated aging have been described in one strain each of Ku80- and DNA-PKcs-deficient mice”
The paper relies on this without support.
Patients with specific mutations in XPD suffer from trichothiodystrophy (TTD), a disease characterized by photosensitivity, brittle hair, skin defects, and a shortened life span.
“Patients with specific mutations in XPD suffer from trichothiodystrophy (TTD), a disease characterized by photosensitivity, brittle hair, skin defects, and a shortened life span.”
The paper relies on this without support.
Cells derived from TTD patients show NER defects.
“In addition, cells derived from TTD patients show NER defects”
The paper relies on this without support.
XPDTTD/XPA double mutants show a much more rapid degenerative phenotype than XPDTTD single mutants.
“XPDTTD/XPA double mutants show a much more rapid degenerative phenotype”
The paper relies on this without support.
The gene defective in WS, WRN, encodes a helicase of the RecQ family.
“The gene defective in WS, WRN, encodes a helicase of the RecQ family (a group defined by its similarity to E. coli RecQ helicase).”
The paper relies on this without support.
WRN possesses an exonuclease domain.
“WRN also possesses an exonuclease domain.”
The paper relies on this without support.
SIRT1 is the most highly related mammalian Sir2 family member to S. cerevisiae Sir2.
“SIRT1 is the most highly related to S. cerevisiae Sir2.”
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
“Long-lived animals share enhanced DNA repair3,5,9–11, reduced molecular error rates and other processes6,12–14.”
From A damage accumulation model identifies distinct aging regimes across species (2026) · cites this paper as [3]
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
“Reduced production of senescent cells in long-lived mammals can be due to enhanced repair of cellular damage, such as double-stranded breaks3,9–11,58.”
From A damage accumulation model identifies distinct aging regimes across species (2026) · cites this paper as [3]
Experimental — accuracy not yet measuredIn the citing paper
“quiescent stem cells can also be subjected to DNA damage during normal homeostatic turnover, and quiescent stem cells depend on DNA repair mechanisms for survival123.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [123]
In the citing paper
“Defects in DSB repair can result in cell cycle arrest, apoptosis or genomic aberrations and have been linked to both disease progression and a premature onset of aging phenotypes (2,3).”
From Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability (2016) · cites this paper as [3]
In the citing paper
“so many mouse models with deletions of genes linked to repairing or sensing DNA damage can exhibit both cancer susceptibility and progeroid features 40”
From The common biology of cancer and ageing (2007) · cites this paper as [40]
Citations
Cites
Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413
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
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510
Oxidative Stress, Caloric Restriction, and Aging
Sohal, R. S., & Weindruch, R. H. (1996) · Science · doi:10.1126/science.273.5271.59 · Cited by 3,133
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
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874
Sirtuin activators mimic caloric restriction and delay ageing in metazoans
Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004) · Nature · doi:10.1038/nature02789 · Cited by 1,868
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Kim, S. H., Kang, Y. W., Lee, J., Kim, H.-K., Jung, B. C., Kim, B., Kim, D. J., & Kim, Y. S. (2016) · Journal of Experimental & Biomedical Sciences/Biomedical Science Letters · doi:10.15616/bsl.2016.22.1.18 · Cited by 1
Molecular Basis of Human Malignancy
Dunn, I. F., & Hahn, W. C. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-3431-5.00003-0 · Cited by 1
Vidya, A., Pattar, S., Roopa, M. S., Venugopal, K. R., & Patnaik, L. M. (2018) · Springer eBooks · doi:10.1007/978-3-319-75683-7_19 · Cited by 1
A-type lamins and Hutchinson-Gilford progeria syndrome pathogenesis and therapy
Andrés, V. (2011) · Frontiers in Bioscience-Scholar · doi:10.2741/s216 · Cited by 2
EFFECTS OF DIET ON CCL11 EXPRESSION AND AGING OF LUNGS AND TESTES OF MICE
Rehman, S. U., Nadeem, S., Zaman, H., Aslam, M. S., & Abbas, Z. (2022) · The Journal of Animal and Plant Sciences · doi:10.36899/japs.2023.1.0593 · Cited by 1
Hemagirri, M., Chen, Y., Gopinath, S. C. B., Adnan, M., Patel, M. B., & Sasidharan, S. (2024) · Biogerontology · doi:10.1007/s10522-024-10104-y · Cited by 2
Methods to Study the Role of Sirtuins in Genome Stability
Martínez‐Redondo, P., & Vaquero, A. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-637-5_18 · Cited by 1
Regulating the levels of key factors in cell cycle and DNA repair
Redwood, A. B., González-Suárez, I., & Gonzalo, S. (2011) · Cited by 1
Alternations in miRNA Expression in Chronic Stress-Induced Ageing of Leydig Cells
Zhou, L., Chen, Q., Wen, X., Xue, S., Lyu, Q., Kuang, Y., & Chai, W. (2017) · Andrology-Open Access · doi:10.4172/2167-0250.1000187 · Cited by 1
Bhattacharya, S., & Rattan, S. I. S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11426-6 · Cited by 1
Kamenisch, Y., & Berneburg, M. (2012) · Medizinische Genetik · doi:10.1007/s11825-012-0364-6 · Cited by 1
Römer, C. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.110271 · Cited by 2
Reece, A. S., & Hulse, G. K. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1182535 · Cited by 3
Stem Cells in Aging: Influence of Ontogenic, Genetic and Environmental Factors.
Yunis, E. J., Zúñiga, J., Koka, P. S., Husain, Z., Romero, V. A., Stern, J. N. H., & Fridkis‐Hareli, M. (2006) · PubMed · Cited by 1
Emran, S. (2015) · UCL Discovery (University College London) · Cited by 1
Lehmann, J. (2017) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-6267 · Cited by 1
Ellis, D., Martín, F. R., Rodríguez‐López, M., Cotobal, C., Sun, X.-M., Jeffares, D. C., Marguerat, S., Tallada, V. A., & Bähler, J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/522524 · Cited by 1
Morath, J. (2013) · KOPS (University of Konstanz) · Cited by 1
Old-age muscle atrophy : Cellular mechanisms and behavioral consequenses
Altun, M. (2007) · Figshare
Novel Roles for A-Type Lamins in Maintaining Genomic Stability
Redwood, A. B. (2012) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7v40s6k
Yuan, Z. (2007) · Digital Commons - University of South Florida (University of South Florida)
Replication fork stability in mammalian cells
Elvers, I. (2011) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Hematopoietic Stem Cell Aging and Fate Decision
Illing, A., & Ju, Z. (2010) · Else Kröner-Fresenius Symposia · doi:10.1159/000312645
Avaliação da expressão de genes processadores de danos oxidativos em pacientes com Alzheimer
de Oliveira, D. V. N. P. (2007) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2007.tde-17042009-152311
Stammzellen als Jungbrunnen? Tissue engineering
Lepperdinger, G. (2007) · Biologie in unserer Zeit · doi:10.1002/biuz.200610336
Biologia molecolare dell’invecchiamento cutaneo intrinseco ed estrinseco
Terranova, F., & Bartoletti, A. (2008) · EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei · doi:10.1016/s1776-0313(08)70406-4
Repair of Oxidative DNA Damage in Mammalian Cells
Ide, H., Matsubara, M., & Katafuchi, A. (2006) · Seibutsu Butsuri · doi:10.2142/biophys.46.263
Molecular and genetic influence of HMGA1 proteins on nucleotide excision repair
Adair, J. E. (2005) · Research Exchange (Washington State University)
A Genetic Analysis of Genomic Stability in Caenorhabditis Elegans: A Dissertation
Auclair, M. M. (2007) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/et2k-5z51
Constantinescu, D. (2008) · D-Scholarship@Pitt (University of Pittsburgh)
The Role of PC4 in Oxidative Stress: A Dissertation
Yu, L. (2011) · eScholarship@UMassChan · doi:10.13028/q0af-rm56
The Stem Cell Niche and Its Role in Self-Renewal, Aging, and Malignancy
Breslin, S. J. P., Volk, A. G., & Zhang, J. (2013) · Wiley-VCH eBooks · doi:10.1002/3527600906.mcb.201200010
SURVEY AND SUMMARY Mammalian Base Excision Repair: the Forgotten Archangel
Dianov, G. L. (2012)
A data mining-based approach for investigating the relationship between DNA repair genes and ageing
Freitas, A. A. (2011) · University of Liverpool · doi:10.17638/00001475
Page, M. M. (2011) · Brock University Digital Repository (Brock University)
Polycomb Group of Genes and the Epigenetics of Aging
Mishra, K., & Mishra, R. K. (2009) · Springer eBooks · doi:10.1007/978-1-4419-0639-7_8
Histone deacetylase inhibition-mediated cytotoxicity of oligodendrocytes.
Dincman, T. A. (2011) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/351
Hodgson, M. E. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/8z3p-d176
The Mechanism of Precise Genome Engineering in Human Cells
Kan, Y. (2015) · University of Minnesota Digital Conservancy (University of Minnesota)
Cardiac Aging in Female Wistar Rat Models With Sedentary or Physicaly Active Lifestyle
Hoffmann, M. (2013) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/qtk2-ae50
Anti-aging Medicine in the eyes of Basic Medicine
Ishii, N. (2011) · Health Evaluation and Promotion · doi:10.7143/jhep.38.223
Der Zellzyklus: Lebenszyklus einer Zelle
Behl, C., & Ziegler, C. (2015) · Springer eBooks · doi:10.1007/978-3-662-48250-6_2
Theorien und Mechanismen des Alterns
Behl, C., & Ziegler, C. (2015) · Springer eBooks · doi:10.1007/978-3-662-48250-6_3
Saha, S. (2015) · eScholarship@McGill (McGill) · doi:10.82308/7943
Aging of Mammalian Intestinal Stem Cells
Sperka, T., & Rudolph, K. L. (2015) · Springer eBooks · doi:10.1007/978-3-7091-1232-8_9
Cho, M., & Suh, Y. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-411596-5.00012-5
Nucleolar Contributions to DNA-Damage Response and Genomic (In)Stability in the Nervous System
Hetman, M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803309-8.00030-6
Is Age Just a Number? Accounting for Age When Designing Viral Vectors for Parkinson's Disease
Polinski, N. K. (2016) · Michigan State University Libraries · doi:10.25335/m5g462
The role of the nucleolus in neurodegeneration.
Hallgren, J. (2016) · doi:10.18297/etd/2547
Pedagogía de la longevidad: proyectar un envejecimiento exitoso
González, X. M. G. (2016) · doi:10.35376/10324/22167
Leandro, G. D. S. (2017) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2017.tde-04012017-141718
Tai, L., Huang, C.-J., Choo, K., Wong, C., Cheong, S. K., & Abidin, T. T. Z. (2017) · Cytotherapy · doi:10.1016/j.jcyt.2017.02.282
THE MULTIFACETED ROLE OF EXONUCLEASE 1 IN DNA REPAIR AND ADULT STEM CELL POPULATIONS
Desai, A. B. (2014) · OhioLink ETD Center (Ohio Library and Information Network)
The roles of transcription factors in Nucleotide excision repair in yeast
Ding, B. (2010) · Louisiana State University · doi:10.31390/gradschool_dissertations.3791
Boosting ATM Activity Promotes Longevity in Nematodes and MicePreprint
Qian, M., Liu, Z., Peng, L., Meng, F., Tang, X., Ao, Y., Shi, L., Zhou, M., Wang, M., Qin, B., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/240606
Lovejoy, T. I. (2013) · Springer eBooks · doi:10.1007/978-1-4419-1005-9_631
Cellular uptake and actions of bilberry anthocyanins in retinal pigment epithelial cells
Milbury, & Everett, P. (2006) · University of New Hampshire Scholars Repository (University of New Hampshire at Manchester)
Girard, M.-J. (2013) · Corpus Université Laval (Université Laval)
Pulmoner hipertansiyonlu hastalarda comet analizi ile değerlendirilen artmış DNA hasarı
Kılıç-Toprak, E., Yaylalı, Y. T., Özdemir, Y., Küçükatay, V., Şenol, H., & Bor-Küçükatay, M. (2019) · Pamukkale Medical Journal · doi:10.31362/patd.557153
Senėjimo molekuliniai mechanizmai ir įtaka kvėpavimo takų ligoms
Januškevičius, A., & Lavinskienė, S. (2015) · Pulmonology and allergology · doi:10.37499/pia.311
Interactions between DNA damage and metabolism
Guevara, A. (2020) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.123699652
Genomics of Aging and Longevity
Falah, G., Gutman, D., & Atzmon, G. (2019) · Springer eBooks · doi:10.1007/978-3-319-69892-2_730-1
da Silva, L. E. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.46.2019.tde-10032020-134305
The cellular senescence unification model and telomerase therapy: To treat all age-related diseases
Liebich, S. (2020) · Aging Pathobiology and Therapeutics · doi:10.31491/apt.2020.09.030
Exploring novel therapeutic strategies in neuroblastoma
Szydzik, J. (2020) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Molecular and Cellular Phenotypes of Cardiovascular Aging
Marı́n-Garcı́a, J., Goldenthal, M. J., & Moe, G. W. P. L. (2007) · Springer eBooks · doi:10.1007/978-0-387-74072-0_4
DNA damage and repair in aging
Kawale, A. S., & Sung, P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-815962-0.00002-0
Der Sonderforschungsbereich 728 „Umweltinduzierte Alterungsprozesse“
Krutmann, J., & Boege, F. (2021) · De Gruyter eBooks · doi:10.1515/9783110718836-051
Fu, S., Hu, J., Chen, X., Li, B., Shun, H., Deng, J., Zhang, Y., Yao, Y., & Zhao, Y. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3742270
Niehaus, C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85679-9.00029-5
Development of Antitumor Cellular Immunity
Welters, M. J. P., & van der Burg, S. H. (2013) · Springer eBooks · doi:10.1007/978-94-007-6217-6_5
Oligonucleotide-mediated gene editing of Apolipoprotein A-I
Disterer, P. (2008) · OpenGrey (Institut de l'Information Scientifique et Technique) · doi:10.13140/rg.2.2.33176.80648
Heinz, D. (2021) · Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) · doi:10.21248/gups.65210
Genomics of Aging and Longevity
Falah, G., Gutman, D., & Atzmon, G. (2021) · Springer eBooks · doi:10.1007/978-3-030-22009-9_730
Itahana, K., & Dimri, G. P. (2008) · Elsevier eBooks · doi:10.1016/b978-012373960-5.00106-4
Ghosh, S. (2019) · Springer theses · doi:10.1007/978-981-32-9267-3_1
Radenković, D., Zhavoronkov, A. A., & Bischof, E. Y. (2022) · Springer eBooks · doi:10.1007/978-3-030-64573-1_248
Mobasheri, A. (2014) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718267258.793490814
Toescu, E. C. (2020) · Springer eBooks · doi:10.1007/978-3-030-39903-0_447
Wang, X., Fan, L., Wang, X., Ge, P., & Liu, L. (2022) · Research Square · doi:10.21203/rs.3.rs-1379941/v1
Scott, B. R., Tokarskaya, Z. B., Zhuntova, G. V., Osovets, S. V., & A, B. A. B. (2007) · doi:10.2172/923839
Toescu, E. C. (2013) · Springer eBooks · doi:10.1007/978-1-4419-1005-9_447
Polo, S. E., & Caron, P. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735233641.793563131
Multiple-Pathway Analysis of Double Strand Break Repair Mutations in Drosophila
Johnson-Schlitz, D. M., Flores, C., & Engels, W. R. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0030050.eor
Yaffe, M. B. (2006) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1031478.363768
Pastink, A., & Zdzienicka, M. Z. (2005) · Springer eBooks · doi:10.1007/3-540-29623-9_2000
Toescu, E. C. (2019) · Springer eBooks · doi:10.1007/978-1-4614-6439-6_447-2
SIRT1 Phosphorylation and Cell Proliferation
Sasaki, T. (2007) · doi:10.18130/v3q85g
van de Ven, M., Andressoo, J., Holcomb, V. B., Lindern, M. V., Jong, W. M. C., Zeeuw, C. I. D., Suh, Y., Hasty, P., Hoeijmakers, J. H. J., van der Horst, G. T. J., et al. (2008) · PLoS Genetics · doi:10.1371/annotation/31502636-9bdf-4cb1-b995-4a30a607e316 · Cited by 1
Pillai, R. K., Miró‐Mur, F., Alijotas‐Reig, J., Tchkonia, T., Schwartz, S., Kirkland, J. L., & Oshima, J. (2022) · Research Square · doi:10.21203/rs.3.rs-2106211/v1
Xia, Q., Cheng, Y., Ma, L., Lu, Z., Lu, Q., zeng, N., wang, Z., & Luo, D. (2022) · Research Square · doi:10.21203/rs.3.rs-2237515/v1
Taatjes, D. J., & Roth, J. (2023) · Histochemistry and Cell Biology · doi:10.1007/s00418-023-02179-4
Kim, I. A., Shin, J. H., Kim, I. H., Kim, J. H., Js, K., Wu, H. G., Chie, E. K., Ha, S. W., Park, C. I., & Kao, G. D. (2023) · doi:10.1158/1078-0432.c.6518577.v1
Metadata
- Authors
- Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W.
- Affiliations
- Brigham and Women's Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Alt, Frederick W.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 120
- Issue
- 4
- Pages
- 497-512
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2022572059
- Cited by
- 944
- References
- 115
- Citations by year
- 2026: 20 · 2025: 40 · 2024: 27 · 2023: 35 · 2022: 39 · 2021: 51 · 2020: 40 · 2019: 46 · 2018: 29 · 2017: 37 · 2016: 38 · 2015: 41 · 2014: 54 · 2013: 51 · 2012: 43
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- aging, DNA repair, genome stability, DNA damage accumulation, premature aging, DNA damage response, Sir2, sirtuins, metabolism, mouse mutants
- MeSH terms
- Ku Autoantigen, Animals, DNA Damage, DNA Repair, DNA-Binding Proteins, Longevity, Tumor Suppressor Protein p53, Cellular Senescence, Reactive Oxygen Species, Antigens, Nuclear, Sirtuins, Genomic Instability, Rad51 Recombinase, Mice
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