The DOI matches its Crossref record; 62 of the 66 references it cites were found in a registry or an index; 33 of the 56 sources its claims cite were checked for support.
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype
Open accessAbstract
Cellular senescence permanently arrests cell proliferation, often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Loss of mitochondrial function can drive age-related declines in the function of many post-mitotic tissues, but little is known about how mitochondrial dysfunction affects mitotic tissues. We show here that several manipulations that compromise mitochondrial function in proliferating human cells induce a senescence growth arrest with a modified SASP that lacks the IL-1-dependent inflammatory arm. Cells that underwent mitochondrial dysfunction-associated senescence (MiDAS) had lower NAD+/NADH ratios, which caused both the growth arrest and prevented the IL-1-associated SASP through AMPK-mediated p53 activation. Progeroid mice that rapidly accrue mtDNA mutations accumulated senescent cells with a MiDAS SASP in vivo, which suppressed adipogenesis and stimulated keratinocyte differentiation in cell culture. Our data identify a distinct senescence response and provide a mechanism by which mitochondrial dysfunction can drive aging phenotypes.
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83 Own result · 38 Own interpretation · 15 Partly supported · 11 No full text of the sources · 7 Supported · 3 Not checked yet · 3 Own method · 2 Sources not found · 1 Supported so far · accuracy not yet measured
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In the paper
“The permanent growth arrest can deplete progenitor or stem cell pools, thereby compromising tissue repair and regeneration”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Partly supportedcites Kuilman et al., 2010 sourceExperimental — accuracy not yet measured
The ‘Replicative cellular senescence’ and ‘Cell cycle arrest’ sections describe senescence as a stable, long-term loss of proliferative capacity. Our copy does not say that this arrest depletes progenitor or stem cell pools or consequently compromises tissue repair and regeneration. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites Sousa-Victor et al., 2014 source
- Partly supportedcites Velarde et al., 2015 sourceExperimental — accuracy not yet measured
The Abstract reports irreversible senescence-associated growth arrest, and the Results link epidermal stem-cell depletion in older Sod2-deficient mice to delayed wound healing. The paper does not establish that the growth arrest itself caused the depletion; it attributes the depletion to Sod2 deficiency and notes that the impaired healing appears only in older mice. (LLM, conf=0.82)
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.
- Partly supported
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In the paper
“indicating that an absence of SIRT3 throughout embryogenesis and acute loss of SIRT3 after development can have different effects, as reported”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
What the sources say
- Partly supportedcites Fernandez-Marcos et al., 2012 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says germline Sirt3 knockout is present from the beginning of embryonic development, whereas the tissue-specific deletions begin at a later developmental stage, and says this timing difference should be considered when comparing outcomes. It does not establish that those tissue-specific deletions occurred acutely after development; tissue specificity and other experimental differences also distinguish the models. (LLM, conf=0.84)
hedgedcorrelational- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“p53 can suppress NF-κB (Dey et al., 2007; Murphy et al., 2011), which promotes transcription of many SASP genes (Freund et al., 2011).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
What the sources say
- Not checked — no full text of the sourcecites Dey et al., 2007 source
- Partly supportedcites Murphy et al., 2011 sourceExperimental — accuracy not yet measured
The Results show that loss of p53 impairs glucocorticoid receptor (GR) repression of NF-κB. The paper supports a role for p53 in suppressing NF-κB in that context, but does not establish that p53 suppresses NF-κB independently of GR and glucocorticoids. Page numbers were not available in our copy. (LLM, conf=0.84)
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Because p53 also limits SASP gene expression (Coppé et al., 2008; Rodier et al., 2009), we depleted p53 in WT and rho0 cells and measured IL1A and IL1B mRNA levels.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
What the sources say
- Partly supportedcites Coppé et al., 2008 sourceExperimental — accuracy not yet measured
In “Cell-Nonautonomous Tumor-Suppressive Function of p53” (page not provided), the paper reports that p53 restrains the SASP: p53-deficient senescent cells secrete higher levels of SASP factors. Those results concern the secretory phenotype, not a demonstrated reduction in SASP gene expression or IL1A/IL1B mRNA by p53. (LLM, conf=0.84)
- Partly supportedcites Rodier et al., 2009 sourceExperimental — accuracy not yet measured
The passage describing the p53-inactivation experiments (section labelled Abstract; page unavailable) reports that loss of p53 increased secreted IL-6 in HCA2 fibroblasts, consistent with p53 limiting at least one SASP factor. It measures cytokine secretion, however, not SASP gene expression generally or the IL1A and IL1B mRNA levels mentioned in the citing sentence. (LLM, conf=0.85)
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.
- Partly supported
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In the paper
“Other reports show that inducible SIRT3 knockout mice do not necessarily phenocopy germline knockout animals (Fernandez-Marcos et al., 2012), consistent with our finding that acute SIRT3 depletion induces senescence.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
What the sources say
- Partly supportedcites Fernandez-Marcos et al., 2012 sourceExperimental — accuracy not yet measured
The Discussion reports that muscle- and liver-specific Sirt3 knockout mice did not show the metabolic phenotypes described in germline knockouts. But the Methods describe tissue-specific Cre lines, not inducible knockout mice. The paper also reports acute Sirt3 deletion in cultured hepatocytes, not in mice, so it does not establish the claim specifically for inducible mice. (LLM, conf=0.86)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our data from POLGD257A mice indicate that MiDAS can occur in vivo, although mtDNA mutations accumulate with age at rates well below that seen in POLGD257A mice (Khrapko and Vijg, 2009).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
What the sources say
- Supportedcites Khrapko and Vijg, 2009 source
The section “Does premature aging in mtDNA mutator mice imply that mtDNA mutations cause normal aging?” (page unavailable) describes Polg mutator mice as having increased mtDNA mutation rates and reports mutation levels in homozygous whole-body mutators one to two orders of magnitude above those in normally aged mice or humans. The comparison supports the claim, although the paper reports measured mutation frequencies rather than a direct estimate of accumulation rates. (LLM, conf=0.90)
plain- 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.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which suppressed adipogenesis and stimulated keratinocyte differentiation in cell culture.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > Abstract
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.
- Rests on an assumption: The effects of the MiDAS SASP on adipocyte and keratinocyte differentiation measured in culture are relevant to aging phenotypes in vivo.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other mitochondrial perturbations induced a similar senescent phenotype, which we term mitochondrial dysfunction-associated senescence (MiDAS).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“depletion of SIRT3 or SIRT5, but not other SIRTs, induced senescence as judged by increased SA-Bgal activity and decreased BrdU labeling 10 days later.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells that underwent mitochondrial dysfunction-associated senescence (MiDAS) had lower NAD+/NADH ratios”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > Abstract
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.
- Probably not a substantial claim. 20
- It may state two separate claims as one. 60
- The quote only partly states this claim. 2
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Notably, NAD+ declines with age in several tissues”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Supportedcites Braidy et al., 2011 source
The Abstract reports a significant age-related decline in intracellular NAD+ in the heart, lung, liver, and kidney of female Wistar rats. The Discussion likewise reports declining NAD+ levels with aging in those organs. (LLM, conf=0.93)
- Partly supportedcites Gomes et al., 2013 sourceExperimental — accuracy not yet measured
In Results, under “Nuclear NAD+ Levels Regulate Mitochondrially Encoded Genes” (page unavailable), the paper reports less total NAD+ in the skeletal muscle of elderly mice and describes an overall age-related decline. It does not establish the citing sentence’s more specific claim that NAD+ declines in several tissues. (LLM, conf=0.86)
- Supportedcites Stein and Imai, 2014 source
The Introduction states that NAD+ levels decline with age in multiple peripheral tissues. The Results also report an age-related decline in mouse hippocampal NAD+ levels. No page numbers are provided in our copy. (LLM, conf=0.94)
plaincorrelational- 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. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“sustained activation of 5′AMP-activated protein kinase (AMPK), a major bioenergetic sensor, is a hallmark of senescence (Moiseeva et al., 2009) and can induce a senescence arrest”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Partly supportedcites Moiseeva et al., 2009 sourceExperimental — accuracy not yet measured
The Results (page not provided) show that AMPK was highly active in Ras-senescent cells compared with control cells, and that RISP knockdown both activated AMPK and produced senescent features. This supports an association in the studied models, but does not establish sustained AMPK activation as a hallmark of senescence generally. The citation is attached to the hallmark clause, not the subsequent claim that AMPK activation can induce arrest. (LLM, conf=0.84)
- Not matchedcites Jiang et al., 2013b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Jones et al., 2005 source
plaindirect- 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. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Dysfunctional mitochondria accumulate with age, best documented in tissues comprised largely of post-mitotic cells”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Herbst et al., 2007 source
- Partly supportedcites Lee et al., 2010 sourceExperimental — accuracy not yet measured
The Results (page unavailable) report age-associated reductions in muscle mitochondrial function in old mice, supporting the claim's general point about aging and dysfunction. They do not establish that dysfunctional mitochondria accumulate or that the pattern is best documented in largely post-mitotic tissues; the reported mitochondrial density in soleus muscle decreased with age. (LLM, conf=0.84)
- Partly supportedcites Safdar et al., 2010 sourceExperimental — accuracy not yet measured
The Introduction reports that older adults’ skeletal muscle shows an accumulation of mitochondrial abnormalities, and the Discussion reports accumulated mtDNA mutations and deletions in older muscle. Neither passage says that accumulation is best documented in tissues composed largely of post-mitotic cells; the paper also notes that age-related changes in mitochondrial function in human muscle remain equivocal. (LLM, conf=0.84)
boostedcorrelational- 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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“it induced cell death after SIRT1-depletion (not shown), as reported”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
What the sources say
- Supportedcites Cheng et al., 2003 source
The Results section reports ionizing-radiation-induced apoptosis in SIRT1-deficient mouse thymocytes, with greater radiation sensitivity than in control thymocytes. The finding concerns thymocytes; the paper does not report the same increased sensitivity in embryonic fibroblasts. (LLM, conf=0.88)
- Supportedcites Yuan et al., 2012 source
Figure 4E (captioned under Cell viability assay; page unavailable) describes A549 cells treated with ionizing radiation and their apoptotic population measured 48 hours later. The section “DBC1 phosphorylation is important for cellular stress response” identifies the Figure 4E cells as depleted of SIRT1 and discusses their DNA damage-induced apoptosis. (LLM, conf=0.85)
plaindirect- 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.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Dysfunctional mitochondria can induce cellular senescence in culture (Moiseeva et al., 2009; Wang et al., 2003) and in vivo (Dai et al., 2010; Kang et al., 2013).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Supportedcites Moiseeva et al., 2009 source
Moiseeva et al. is cited for the culture portion of the sentence, not the in vivo portion. The Results report that interfering with mitochondrial function induced senescence markers, and the Discussion states that disrupting electron transport or oxidative phosphorylation was sufficient to trigger senescent cell-cycle arrest in human cells. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites Wang et al., 2003 source
- Supportedcites Dai et al., 2010 source
Dai et al. is cited for the in vivo portion of the sentence, not the culture portion. In the Results section, older mitochondrial mutator mouse hearts had approximately threefold higher expression of the senescence marker p16INK4a than wild-type hearts, and mitochondrial-targeted catalase partially reduced it. (LLM, conf=0.88)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This senescence-associated secretory phenotype (SASP) comprises pro-inflammatory cytokines, proteases, and growth and angiogenesis factors”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Partly supportedcites Coppé et al., 2008 sourceExperimental — accuracy not yet measured
The Discussion describes inflammatory cytokines and growth factors as SASP components and says chronic SASP secretion may disrupt normal tissue structure and function. The passages retrieved from our copy do not establish proteases or angiogenesis factors as SASP components, so the composition stated in the citing sentence is only partly supported. (LLM, conf=0.82)
plaindirect- 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. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Increased ADP:ATP or AMP:ATP ratios activate AMPK (Hardie et al., 2012)”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Low NAD+/NADH Ratios Drive MiDAS through AMPK
What the sources say
- Supportedcites Hardie et al., 2012 source
The Introduction states that AMPK senses increases in both AMP:ATP and ADP:ATP ratios. The ‘AMPK – subunits and regulation’ section explains that AMP activates AMPK allosterically, while both AMP and ADP can promote its activation through effects on phosphorylation. (LLM, conf=0.94)
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.
Probably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Since p53 inhibits RELA by competing for CBP binding (Webster and Perkins, 1999), p53 likely limits the IL1 arm of the SASP by reducing NF-κB activity.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
What the sources say
- Supportedcites Webster and Perkins, 1999 source
The Results report that p53 inhibits RelA-mediated transcription and that adding CBP reverses this inhibition. The Discussion states that p53 and RelA bind p300 and CBP competitively, while noting that this mechanism may only partially explain their transcriptional cross talk. The cited claim concerns RelA activity; the sentence’s subsequent inference about the SASP is not attributed to this source. (LLM, conf=0.91)
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.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Notably, many SASP factors that were not expressed by SIRT3-depleted cells are pro-inflammatory, although the cells uniquely secreted CCL27”
- Also stated in: § Mitochondrial SIRTs Suppress Senescent Phenotypes · plain
“a pro-inflammatory cytokine that comprises the SASP of mouse, but not human, fibroblasts induced to senesce by IR”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
What the sources say
- Partly supportedcites Coppé et al., 2010 sourceExperimental — accuracy not yet measured
The Introduction and Discussion describe inflammatory cytokines as SASP factors, supporting the general characterization of many SASP factors as pro-inflammatory. The Results discuss CCL-family factors in irradiated mouse and human fibroblasts, but the passages found do not identify CCL27 as present in the mouse SASP and absent from the human SASP. The paper does not address SIRT3-depleted cells; their secretion profile is the citing authors’ own finding. (LLM, conf=0.78)
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.
- Also stated in: § Mitochondrial SIRTs Suppress Senescent Phenotypes · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“IR robustly activates p53, which subsides to a low chronic level in 7–10 days as the SASP develops (Coppé et al., 2008; Rodier et al., 2009).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
What the sources say
- Partly supportedcites Coppé et al., 2008 sourceExperimental — accuracy not yet measured
The Results passage discussing Figure 1D and Figure S3 reports p53 stabilization and phosphorylation after irradiation, and says a robust SASP developed 4–7 days later. The passage discussing Figure 6G also gives 4–7 days for cells with wild-type p53. Neither passage says p53 subsided to a low chronic level in 7–10 days. (LLM, conf=0.86)
- Partly supportedcites Rodier et al., 2009 sourceExperimental — accuracy not yet measured
The passage labeled Abstract (page unavailable; Fig. 1a–c) reports rapid p53 activation after irradiation, and another passage reports that inflammatory cytokine secretion develops after a delay following a senescence-inducing dose. It does not establish that p53 subsides to a low chronic level at 7–10 days: the reported return toward baseline within 10 hours concerns a low dose from which cells recovered, while cytokine secretion reached senescent levels within 3–5 days. (LLM, conf=0.87)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“or stabilizing p16INK4a mRNA (Chang et al., 2010)”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Low NAD+/NADH Ratios Drive MiDAS through AMPK
What the sources say
- Partly supportedcites Chang et al., 2010 sourceExperimental — accuracy not yet measured
The Results and Discussion (page not provided) link increased p16 mRNA stability with replicative senescence and describe HuR-mediated p16 mRNA decay. They do not show that AMPK activation stabilizes p16 mRNA or induces senescence through that mechanism. (LLM, conf=0.85)
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.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We reported that elevated oxygen dampens the SASP in humans and mouse cells (Coppé et al., 2010; Parrinello et al., 2003).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
What the sources say
- Partly supportedcites Coppé et al., 2010 sourceExperimental — accuracy not yet measured
The Results section on mouse fibroblast SASPs reports that 20% oxygen suppresses the SASP in mouse cells compared with 3% oxygen. It also says oxygen had only minor effects on senescent human cells, which developed robust SASPs at both concentrations. The claim is supported for mouse cells but not for human cells. (LLM, conf=0.91)
- Could not verifycites Parrinello et al., 2003 sourceExperimental — accuracy not yet measured
The paper’s Abstract (page unavailable) compares how 3% and 20% oxygen affect senescence, proliferation, and DNA damage in mouse and human fibroblasts. Searches for SASP, secretory phenotype, secretion, and cytokines found no passage addressing whether elevated oxygen dampens the SASP. (LLM, conf=0.75)
plaindirect- 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Mitochondrial ROS can damage nuclear DNA, thus activating a DNA damage response that induces senescence (Moiseeva et al., 2009; Passos et al., 2010).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
What the sources say
- Supportedcites Moiseeva et al., 2009 source
The Results report oxidative DNA damage in the nuclei of Ras-expressing cells alongside mitochondrial ROS production. The Discussion says ROS-related damage to nuclear DNA could activate p53 and Rb, sustaining pathways involved in senescence. This supports the claim as a possible mechanism, rather than one the paper establishes as the sole cause of senescence. (LLM, conf=0.88)
- Supportedcites Passos et al., 2010 source
The Introduction (page unavailable) says ROS can directly damage DNA, inducing a DNA damage response and senescence. The Results and Discussion (pages unavailable) connect mitochondrial dysfunction and ROS production to renewed DNA damage foci and the maintenance of senescent growth arrest. (LLM, conf=0.90)
plaindirect- 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. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Our finding that loss of SIRT3 loss drives senescence appears to contradict a report in which cells from SIRT3 knockout mice were highly susceptible to oncogenic transformation; however, this susceptibility depended on the elevated ROS characteristic of sirt3−/− cells (Kim et al., 2010).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
What the sources say
- Partly supportedcites Kim et al., 2010 sourceExperimental — accuracy not yet measured
The Results sections on transformation and SOD report that SIRT3−/− mouse embryonic fibroblasts were transformed by a single oncogene and that MnSOD prevented their immortalization by Myc or Ras alone. The claim overgeneralizes the ROS dependence: MnSOD did not prevent immortalization when the cells expressed both Myc and Ras. The paper also reports normal superoxide levels in unstressed knockout cells, rather than uniformly elevated levels. (LLM, conf=0.87)
plaindirect- 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. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Mitochondrial dysfunction has been linked to aging (Khrapko and Vijg, 2009), but it is not clear how it drives aging, particularly in mitotic tissues.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
What the sources say
- Supportedcites Khrapko and Vijg, 2009 source
The section “Mitochondria: molecular clocks of aging?” describes a proposed central role for mitochondria in aging. “Dividing tissues: mtDNA mutations in stem cells” calls mutation accumulation an attractive candidate aging mechanism while noting that its causal role remains unproven. These passages support the cited link without claiming that the mechanism is settled; page numbers were not provided. (LLM, conf=0.92)
plaincorrelational- 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, they secreted HMGB1, a pro-inflammatory alarmin that is a feature of senescent cells (Davalos et al., 2013).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
What the sources say
- Supportedcites Davalos et al., 2013 source
The Introduction states that HMGB1 is an alarmin that provokes an innate immune response and that senescent cells secrete it early after a senescence-inducing stimulus. The Discussion likewise identifies HMGB1 as an alarmin and reports its active secretion by senescent cells, linking it to their inflammatory activity. (LLM, conf=0.94)
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. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These data support the findings that epidermal-specific SOD2-deficient mice rapidly accumulate senescent keratinocytes, which show enhanced differentiation (Velarde et al., 2015) and that POLGD257A mice have a thicker stratum corneum and lipodystrophy compared to age-matched WT mice (Trifunovic et al., 2004).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > MiDAS in POLG Mice
What the sources say
- Partly supportedcites Velarde et al., 2015 sourceExperimental — accuracy not yet measured
The Results report increased senescence markers in epidermal keratinocytes after Sod2 deletion and enhanced keratinocyte differentiation at wound sites in young mice. However, senescence was assessed four months after deletion, so the paper does not establish that senescent keratinocytes accumulated rapidly; it also does not show that the senescent cells specifically were the ones with enhanced differentiation. (LLM, conf=0.83)
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. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SIRT3 depletion induced three senescence markers: reduced lamin B1 (LMNB1) levels”
- Also stated in: § Mitochondrial SIRTs Suppress Senescent Phenotypes · plain
“decreased nuclear localization of high mobility group protein B1 (HMGB1)”
- Also stated in: § Mitochondrial SIRTs Suppress Senescent Phenotypes · plain
“increased levels of the cell-cycle inhibitor p21WAF1”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Mitochondrial SIRTs Suppress Senescent Phenotypes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we identified the mitochondrial SIRTs SIRT3 and to a lesser extent SIRT5, as suppressors of senescence and modulators of the SASP.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show here that several manipulations that compromise mitochondrial function in proliferating human cells induce a senescence growth arrest with a modified SASP that lacks the IL-1-dependent inflammatory arm.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — 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 phenotypes occurred in cultured human cells and a murine model of premature aging through mitochondrial dysfunction”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite lacking IL-1-dependent SASP factors, the MiDAS SASP suppressed adipocyte differentiation and promoted keratinocyte differentiation.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
plaindirect- 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: The effects of the MiDAS SASP on adipocyte and keratinocyte differentiation measured in culture are relevant to aging phenotypes in vivo.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the induction of other senescence markers, neither SIRT depletion increased IL-6 secretion”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SIRT3-depleted cells failed to express significant levels of the SASP mRNAs encoding IL1B, CXCL1, CXCL2, IL-6, IL-8 and VEGF, but expressed high levels of mRNAs encoding the SASP factors AREG and IL-10, regardless of IR exposure”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IR increased NF-κB activity in WT cells, as reported (Freund et al., 2011), but failed to do so in rho0 cells without pyruvate and reduced NF-κB activity to below that of unirradiated rho0 cells cultured with pyruvate (Figure 5F).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“SIRT3 depletion strongly suppressed IL-6 secretion by cells induced to senesce by IR, NaBu, or Bleo (Figure 1H) and moderately suppressed IL-6 secretion in response to MKK6EE or RAS”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while the NAD+/NADH ratio declined with MiDAS, total NAD+ actually increased”
- Also stated in: § Decreased NAD+/NADH Ratios Mediate MiDAS · plain
“along with a rise in nicotinamide phosphoribosyltransferase (NAMPT) mRNA”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Decreased NAD+/NADH Ratios Mediate MiDAS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An NF-κB reporter showed that NF-κB activity was high in rho0 cells cultured with pyruvate but much lower in rho0 cells without pyruvate (Figure 5F).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, some secreted factors were unaffected by MiDAS and were insensitive to pyruvate.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“pyruvate lowered cytosolic NADH to a much larger degree than in WT cells; it also lowered mitochondrial NADH in rho0 cells, but to a lesser extent than in the cytosol.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — 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 rho0 cells, lactate elicited only a small cytosolic response, suggesting that NADH was already reduced in this compartment.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“when we depleted NAD+ by preventing NAD salvage using the NAMPT inhibitor FK866, cell proliferation ceased after ~7 day”
- Also stated in: § Decreased NAD+/NADH Ratios Mediate MiDAS · plain
“and cells became senescent after ~21 days”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Decreased NAD+/NADH Ratios Mediate MiDAS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upon pyruvate withdrawal, rho0, but not WT, cells rapidly senesced, as measured by low EdU labeling and high SA-Bgal”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial Dysfunction and Senescent Phenotypes
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the antioxidant EUK-134 reduced mitochondrial, but not cytoplasmic, ROS in SIRT3- and HSPA9-depleted cells”
- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
“but did not prevent the growth arrest of these or Rot-treated cells”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial Dysfunction and Senescent Phenotypes
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“FK866 suppressed IR-induced IL-6 secretion (Figure 3I) and lowered total NAD levels (Figure 3J).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiDAS also increased p21WAF1 and p16INK4a and decreased LMNB1 and intracellular HMGB1 protein levels, which were prevented by pyruvate.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Low NAD+/NADH Ratios Drive MiDAS through AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although IR induced a SASP in WT cells with or without pyruvate, rho0 cells plus pyruvate expressed an enhanced SASP that was suppressed by IR (Figures 5E and S5C).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiDAS also increased p21WAF1 and p16INK4a and decreased LMNB1 and intracellular HMGB1 protein levels, which were prevented by pyruvate.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Low NAD+/NADH Ratios Drive MiDAS through AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AOA-treated WT cells underwent senescence (high SA-Bgal, low EdU labeling, loss of nuclear HMGB1; Figures 3D, 3E, S3G, and S3H) but failed to secrete IL-6 following IR, despite slightly higher secretion by unirradiated AOA-treated cells”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All treatments induced senescence as determined by reduced EdU incorporation, increased SA-Bgal activity”
- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
“and loss of nuclear HMGB1 (for rho0 and Rot”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial Dysfunction and Senescent Phenotypes
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“rho0 and SIRT3-depleted cells showed no increase in 53BP1 foci”
- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
“and EUK-134 had no effect on these foci in any senescent cell”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial Dysfunction and Senescent Phenotypes
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“pyruvate lowered NADH in the cytosol, while increasing NADH in mitochondria”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, only MiDAS cells showed marked activation of both AMPKα (thr-172 phosphorylation) and p53 (ser-15 phosphorylation), both of which were blunted by pyruvate (Figure 4C).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Low NAD+/NADH Ratios Drive MiDAS through AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NMN delayed senescence by ~2 day relative to untreated cells (Figure S3I), but both groups senesced within 7 days”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All these manipulations elevated the ADP:ATP ratio (Figure 4A), which was lowered by pyruvate”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Low NAD+/NADH Ratios Drive MiDAS through AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although shSIRT3 and rho0 cells cultured without pyruvate had elevated Mitosox fluorescence”
- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
“normalization to Mito-tracker showed roughly equivalent ROS levels between control and SIRT3-depleted cells”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial Dysfunction and Senescent Phenotypes
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while SIRT3 shRNA induced senescence in wild-type (WT) mouse embryonic fibroblasts (MEFs), MEFs from SIRT3 knockout mice did not senesce”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upon pyruvate withdrawal, expression of these factors declined to near WT levels”
- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
“and the cells arrested growth”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial Dysfunction and Senescent Phenotypes
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Mitochondrial Dysfunction and Senescent Phenotypes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Further, compared to WT, POLGD257A epidermis had more senescent cells in the stratum corneum as judged by SA-Bgal positivity (Figures S6C and S6D) and loss of HMGB1 in suprabasal epidermal nuclei (Figures S6E and S6F).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > MiDAS in POLG Mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — 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 MiDAS, pyruvate, but not an antioxidant, prevented MiDAS, which showed no evidence of DNA damage.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Examples include the pro-inflammatory cytokines CCL27 (Figure 1G) and TNF-α (Figure 5I) and the anti-inflammatory cytokine IL-10 (Figure 5I).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Inguinal adipose tissue (IAT) from 8-month-old POLGD257A mice had more cells with SA-Bgal (Figures 6A, 6C, S6A, and S6B) and loss of nuclear HMGB1 (Figures 6B and 6D) than age-matched WT IAT, primarily in cells between mature adipocytes.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > MiDAS in POLG Mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiDAS cells secreted the anti-inflammatory cytokine IL-10, but also high levels of the pro-inflammatory cytokines CCL27 and TNF-α.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
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
“SIRT3 showed a stronger response, likely because it was more efficiently depleted”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“there is mounting evidence that senescent cells can accumulate with age and cause or contribute to aging phenotypes and pathologies.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
plainconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Rests on an assumption: Cells that become senescent and build up over time are a cause or contributor to age-related phenotypes and disease.
In the paper
“Inhibition of the latter by depletion of malate dehydrogenase lowers the NAD+/NADH ratio and induces a senescence arrest”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Lee et al., 2012 source
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
“Our data identify a distinct senescence response and provide a mechanism by which mitochondrial dysfunction can drive aging phenotypes.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > Abstract
plaindirect- 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: Cells that become senescent and build up over time are a cause or contributor to age-related phenotypes and disease.
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
“We show that MiDAS results from a decreased NAD+/NADH ratio, activation of AMPK and subsequently the tumor suppressor p53, which then limits the IL-1 mediated arm of the SASP.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Because mitochondria oxidize NADH to NAD+ (Lehninger et al., 2013), mitochondrial dysfunction can decrease the NAD+/NADH ratio.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > INTRODUCTION
What the sources say
- Not matchedcites Lehninger et al., 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainconditional- Asserted: passes — The authors put it forward as true.
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- Not matched
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In the paper
“Because p53 initiates the senescence arrest and is an AMPK target (Jiang et al., 2013b; Jones et al., 2005), we assessed the p53 dependence of MiDAS.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
What the sources say
- Not matchedcites Jiang et al., 2013b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites Jones et al., 2005 source
plaindirect- 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.
- Not matched
In the paper
“which can induce senescence by phosphorylating p53 (Jones et al., 2005)”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Low NAD+/NADH Ratios Drive MiDAS through AMPK
What the sources say
- Not checked — no full text of the sourcecites Jones et al., 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Thus, SIRT3 depletion induced senescence but with a SASP that differed from that induced by IR, suggesting a mitochondrial function is required for expression of a subset of SASP factors.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Mitochondrial SIRTs Suppress Senescent Phenotypes
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“IL-1α and IL-1β initiate a positive feedback loop that drives expression of SASP factors such as IL-6 and IL-8 (Orjalo et al., 2009).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > AMPK Mediates MiDAS through p53
What the sources say
- Not checked — no full text of the sourcecites Orjalo et al., 2009 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.
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
“We conclude that low NAD+/ NADH ratios mediate MiDAS phenotypes, which are prevented by NADH oxidation.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > Decreased NAD+/NADH Ratios Mediate MiDAS
plaindirect- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“IMR-90 human fibroblasts were mycoplasma-free, cultured in 3% O2 as described (Coppé et al., 2008; Rodier et al., 2009), and used between 25 and 40 population doublings.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > EXPERIMENTAL PROCEDURES > Cell Culture
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.
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
“MiDAS results from an NADH-AMPK-p53-dependent pathway and elicits a SASP that lacks IL-1-dependent factors but includes others.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Data are presented either as representative examples or means of 3+ experiments.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > EXPERIMENTAL PROCEDURES > Statistical Analysis
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Protocols were approved by the Institutional Animal Care and Use Committee.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > EXPERIMENTAL PROCEDURES > Animals
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.
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
“We show that (1) mitochondrial dysfunction induces a senescence response (MiDAS), including arrested growth and a SASP that is distinct from that caused by genotoxic stress;”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These data support the findings that epidermal-specific SOD2-deficient mice rapidly accumulate senescent keratinocytes, which show enhanced differentiation (Velarde et al., 2015) and that POLGD257A mice have a thicker stratum corneum and lipodystrophy compared to age-matched WT mice (Trifunovic et al., 2004).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > MiDAS in POLG Mice
What the sources say
- Not checked — no full text of the sourcecites Trifunovic et al., 2004 source
plaincorrelational- 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.
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It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“To determine whether MiDAS occurs in vivo, we analyzed POLGD257A mice, which have a mutation in the proofreading domain of the mtDNA polymerase (PolG) and rapidly accumulate mtDNA mutations and aging phenotypes (Kujoth et al., 2005; Trifunovic et al., 2004).”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > RESULTS > MiDAS in POLG Mice
What the sources say
plaindirect- 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
“Because p53 depletion was sufficient to prevent MiDAS, AMPK most likely mediates MiDAS through p53 activation, and subsequent NF-κB inhibition.”
§ Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype > DISCUSSION
hedgedconditional- 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.
The paper relies on this without support.
Cells that become senescent and build up over time are a cause or contributor to age-related phenotypes and disease.
“there is mounting evidence that senescent cells can accumulate with age and cause or contribute to aging phenotypes and pathologies.”
The paper relies on this without support.
The effects of the MiDAS SASP on adipocyte and keratinocyte differentiation measured in culture are relevant to aging phenotypes in vivo.
“which suppressed adipogenesis and stimulated keratinocyte differentiation in cell culture.”
The paper relies on this without support.
It is not clear how mitochondrial dysfunction drives aging, particularly in mitotic tissues.
“Mitochondrial dysfunction has been linked to aging (Khrapko and Vijg, 2009), but it is not clear how it drives aging, particularly in mitotic tissues.”
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
“mitochondrial dysfunction-associated senescence (MiDAs), which is characterized by a distinct phenotype, exhibits a unique cell-non-autonomous programme that is potentially responsible for the altered metabolism and aberrant adipocyte differentiation observed in aged animals47”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [47]
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
“Mouse models of mitochondrial dysfunction and enhanced oxidative stress show increased senescence (Wiley et al., 2016), but a detailed characterization of mitochondrial function in senescent cells in vivo is lacking.”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Wiley et al., 2016
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
“Genetic or pharmacological inhibition of the ETC can induce senescence even though cells lack expression of key pro-inflammatory SASP factors, such as IL-6 and IL-8 (Wiley et al., 2016).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Wiley et al., 2016
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
“NAD + /NADH ratios are reduced in senescent cells (Wiley et al., 2016), which could alter the activity of poly-ADP ribose polymerase (PARP) and sirtuins, both involved in activation of the SASP regulator NF-kB (Birch and Passos, 2017).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Wiley et al., 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The SASP can either suppress differentiation (of preadipocytes) or promote it (of keratinocytes), resulting in alterations such as the lipodystrophy and skin phenotypes common in old mice (Wiley et al. 2016).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Wiley et al. 2016
Experimental — accuracy not yet measured
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
“Cells without a persistent DDR58, such as cells induced to senescence via mitochondrial dysfunction or enforced upregulation of the CDK4/6 inhibitors p16 and p2139,58, do not express these pro-inflammatory SASP factors.”
From Algorithmic assessment of cellular senescence in experimental and clinical specimens (2021) · cites this paper as [39]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Dysfunctional mitochondria may play an important role in senescence establishment, as depletion of mitochondrial sirtuins, a group of evolutionarily conserved proteins that regulate ageing across different species, as well as selective chemical inhibition of mitochondrial function, triggers senescence47”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [47]
The cited source says what the claim attributes to it.
In the citing paper
“Similarly, induction of senescence by mitochondrial dysfunction presents a distinct secretory phenotype (Wiley et al., 2016).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Wiley et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“For example, dysfunctional mitochondria cause a distinct senescence response, termed mitochondrial dysfunction-associated senescence (MiDAS), which lacks the IL-1-dependent proinflammatory arm of the SASP (Wiley et al. 2016).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Wiley et al. 2016
The cited source says what the claim attributes to it.
In the citing paper
“mitochondrial dysfunction can be a direct inducer of senescence 51,52 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [51]
In the citing paper
“Another cause of senescence growth arrest, mitochondrial dysfunction, different from senescence due to genotoxic stress has recently been identified (Wiley et al., 2016).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Wiley et al., 2016
In the citing paper
“The key feature of miDAS is the distinct secretory phenotype, different from canonical SASP caused by genotoxic stress.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Wiley et al., 2016
In the citing paper
“This SASP lacks the canonical IL-1 mediated inflammatory components but comprises interleukin (IL)-10, tumor necrosis factor alpha (TNF-α) and chemokine (C-C motif) ligand 27 (CCL27) (Wiley et al., 2016).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Wiley et al., 2016
In the citing paper
“Mitochondria normally oxidize NADH to NAD+ and mitochondrial dysfunction decreases the NAD+/NADH ratio mostly in the cytosol, leading to activation of 5′ adenosine monophosphate activated protein kinase (AMPK), resulting in p53 activation and mitochondrial dysfunction associated senescence (miDAS) (Wiley et al., 2016).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Wiley et al., 2016
In the citing paper
“Depletion of NAD+ causes loss of efficient sirtuin activity, resulting in impaired functionality of mitochondrial SIRT3, leading to dysregulation in mitochondrial antioxidant systems, mitochondrial DNA (mtDNA) repair, and mitochondrial quality control and biogenesis (SIRT1) pathways, and may also promote senescence (70).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [70]
In the citing paper
“In primary cell culture, supplementation with NR delays cellular senescence (Wiley et al., 2016), and NR treatment also reduces the senescent state in both NSCs and other stem cell types (Zhang et al., 2016).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Wiley et al., 2016
In the citing paper
“NAD+ replenishment delays cellular senescence (including mitochondrial dysfunction-associated senescence)”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Wiley et al., 2016
In the citing paper
“Recent work shows that SIRT3 and SIRT5 attenuate the SASP, in part by preventing dysfunctional decreases in NAD+/NADH ratios ((Wiley et al. 2016)).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Wiley et al. 2016
In the citing paper
“The loss in NRF1 binding appears to account for the reduced expression of mitochondrial respiratory chain genes and defective oxidative phosphorylation that could result in poor T cell survival”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Wiley et al., 2016
In the citing paper
“neutrophils from elderly subjects show a well-preserved capability to ingest non-opsonized particles [24], but a reduced capability to uptake opsonized particles, or pathogens such as Escherichia coli [37,42]”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [24]
In the citing paper
“Senescent cells secrete a distinct suite of inflammatory cytokines and chemokines depending upon whether senescence is induced by genotoxic stress, [23] or mitochondrial dysfunction, as in the form of deficiencies in mitochondrial sirtuins or damage to mitochondrial DNA [24]”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [24]
In the citing paper
“Therefore, mitochondrial dysfunction, initiated by pathways different from DNA damage, can determine the SASP quality because local extracellular factors, such as pyruvate, can modify the SASP in senescent cells [225].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [225]
In the citing paper
“Growth arrest due to these mitochondrial perturbations was rescued by the exogenous supply of the electron acceptors pyruvate and potassium ferricyanide that artificially restore NAD+ levels.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [225]
In the citing paper
“AMPK signaling is also induced by the reduced cytosolic NAD+/NADH ratio as a result of mitochondrial defects [225].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [225]
In the citing paper
“Critically short, uncapped telomeres [9], oncogene stresses [51], and mitochondrial dysfunction [225] result in proliferative stress and senescence induction, thereby halting the proliferation of cells harboring mutations or genomic instability.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [225]
In the citing paper
“Evidence has shown that mitochondrial interventions at multiple regulation steps of the electron transport chain induce a senescent-like phenotype lacking the expression of pro-inflammatory senescence-associated secretory phenotype (SASP) elements, e.g., IL-6 and IL-8 [114,115].”
From Role of Age-Related Mitochondrial Dysfunction in Sarcopenia (2020) · cites this paper as [115]
In the citing paper
“However, we must to understand that the SASP can vary significantly in terms of the quantity and quality of secreted proteins and other factors, depending on the insult used to trigger cell senescence (Maciel‐Baron et al., 2016; Wiley et al., 2016); therefore, the composition of the SASP may be vary depending on the tissue and the insult.”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Wiley et al., 2016
In the citing paper
“Moreover, induction of senescence can occur in the absence of DNA damage, for example as a consequence of mitochondrial dysfunctions39.”
From Algorithmic assessment of cellular senescence in experimental and clinical specimens (2021) · cites this paper as [39]
Self-check
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Self-check results appear here once an independent check has confirmed them.
Cited works that were retracted
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In the paper
“Notably, NAD+ declines with age in several tissues (Braidy et al., 2011; Gomes et al., 2013; Stein and Imai, 2014; Yoshino et al., 2011), linking NAD to both senescence and aging.”
Cited work 10.1371/journal.pone.0019194 · retracted 2024-11-13 · notice 10.1371/journal.pone.0313921 · this paper published 2016-02
Citations
Cites
1 retracted
Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats
Braidy, N., Guillemin, G. J., Mansour, H., Chan-Ling, T., Poljak, A., & Grant, R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019194 · Cited by 594 · cited 1×
“Notably, NAD+ declines with age in several tissues (Braidy et al., 2011; Gomes et al., 2013; Stein and Imai, 2014; Yoshino et al., 2011), linking NAD to both senescence and aging.”
BackgroundRetractedA biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · cited 3×
“Unlike the growth arrest and markers such as senescence-associated b-galactosidase (SA-Bgal) (Dimri et al., 1995), little is known about how mitochondria affect the SASP.”
BackgroundMethodInfluential(1978) · Biochemical Education · doi:10.1016/0307-4412(78)90049-3 · Cited by 5,073
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602 · cited 1×
“Increased ADP:ATP or AMP:ATP ratios activate AMPK (Hardie et al., 2012), which can induce senescence by phosphorylating p53 (Jones et al.”
BackgroundCellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Self-citationAging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 1×
“The senescence response suppresses the development of cancer (Campisi, 2003; Campisi, 2013), but there ismounting evidence that senescent cells can accumulate with age and cause or contribute to aging phenotypes and pathologies.”
BackgroundSelf-citationPremature 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
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
Self-citationMitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085 · cited 1×
“, 2013a) that are linked to aging (Haigis and Sinclair, 2010; Merksamer et al., 2013)—for ability to regulate senescence, we identified the mitochondrial SIRTs SIRT3, and to a lesser extent SIRT5, as suppressors of senescence and modulators of the SASP.”
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Items 501–600 of 1,285
Promises and challenges of senolytics in skin regeneration, pathology and ageing
Pils, V., Ring, N., Valdivieso, K., Lämmermann, I., Грубер, Ф., Schosserer, M., Grillari, J., & Ogrodnik, M. B. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111588 · Cited by 33
The effect of lactoferrin in aging: role and potential
Li, B., Zhang, B., Liu, X., Zheng, Y., Han, K., Liu, H., Wu, C., Li, J., Fan, S., Peng, W., et al. (2021) · Food & Function · doi:10.1039/d1fo02750f · Cited by 32
Restoration of CPEB4 prevents muscle stem cell senescence during aging
Zeng, W., Zhang, W., Tse, E. H. Y., Liu, J., Dong, A., Lam, K. S. W., Luan, S., Küng, W., Chan, T. C., & Cheung, T. H. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.05.012 · Cited by 35
Hino, Y., Nagaoka, K., Oki, S., Etoh, K., Hino, S., & Nakao, M. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac735 · Cited by 31
“Wiley et al . have reported that knockdown of sirtuin 3 (SIRT3), a mitochondrial sirtuin, led to senescence in human fibroblasts which was not accompanied by the expression of proinflammatory cytokines (66).”
Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic
Al-Mansour, F. S. H., Alraddadi, A. M., He, B., Saleh, A., Poblocka, M., Alzahrani, W., Cowley, S. M., & Macip, S. (2023) · Aging · doi:10.18632/aging.204616 · Cited by 30
Okuno, K., Cicalese, S. M., Elliott, K. J., Kawai, T., Hashimoto, T. N., & Eguchi, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186579 · Cited by 28
Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability
Ghosh, J. C., Perego, M., Agarwal, E., Bertolini, I., Wang, Y., Goldman, A. R., Tang, H., Kossenkov, A. V., Landis, C. J., Languino, L. R., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2115624119 · Cited by 29
“Consistent with this parallel, in vivo models of aging have been associated with reduced Mic60 levels (30), heightened SASP signaling (31), mitochondria-tonuclei retrograde gene expression (32), and a general, proinflammatory environment (33).”
BackgroundRoth‐Walter, F., Adcock, I. M., Benito‐Villalvilla, C., Bianchini, R., Bjermer, L. H., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguíluz‐Gracia, I., et al. (2023) · Allergy · doi:10.1111/all.15977 · Cited by 31
“…p21, CDKN1a, cyclin-dependent kinase inhibitor 1A, synonyms: CAP20, CDKN1, CIP1, P21, p21CIP1, p21Cip1/Waf1, SDI1, and WAF1; p53, tumor protein 53, acts as tumor suppressor, induces growth arrest and apotosis; synonyms: LFSA and TP53; PARP, poly(adenosine diphosphate-ribose) polymerase:…”
KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging
Soto‐Heredero, G., Gabandé‐Rodríguez, E., Carrasco, E., Escrig-Larena, J. I., Heras, M. M. G. D. L., Delgado-Pulido, S., Francos-Quijorna, I., Blanco, E. M., Fernández-Almeida, Á., Abia, D., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00855-9 · Cited by 34
“In addition, both mitochondrial decline and cellular senescence are tightly interconnected 31,32 .”
Induction of a Senescence-Like Phenotype in Cultured Human Fetal Microglia During HIV-1 Infection
Chen, N. C., Partridge, A. T., Tüzer, F., Cohen, J., Nacarelli, T., Navas, S., Sell, C., Torres, C. A., & Martín‐García, J. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly022 · Cited by 32
Hellmich, C., Wojtowicz, E. E., Moore, J. A., Mistry, J. J., Jibril, A. S., Johnson, B. B., Smith, J. G. W., Beraza, N., Bowles, K. M., & Rushworth, S. A. (2022) · Blood Advances · doi:10.1182/bloodadvances.2022007033 · Cited by 31
“11 Furthermore, we showed, using the p16-3MR mouse model, that depletion of senescent MSCs had a knock-on effect on the metabolic HPC response to stress.”
Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology
Harutyunyan, A., Harutyunyan, H. A., & Yenkoyan, K. B. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.788779 · Cited by 29
“Thus, diminished NAD de novo synthesis could lead to lower NAD/NADH ratio, mitochondrial dysfunction, and oxidative stress (83).”
BackgroundArnold, R., Vehns, E., Randl, H., & Djabali, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147474 · Cited by 30
“ATP demand is not met, premature cellular SNS or death can occur [58].”
BackgroundRelationship between circulating mitochondrial DNA and microRNA in patients with major depression
Ogata, H., Higasa, K., Kageyama, Y., Tahara, H., Shimamoto, A., Takekita, Y., Koshikawa, Y., Nonen, S., Kato, T., Kinoshita, T., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.07.073 · Cited by 30
Etoh, K., Araki, H., Koga, T., Hino, Y., Kuribayashi, K., Hino, S., & Nakao, M. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114496 · Cited by 31
MiR-665 Regulates Vascular Smooth Muscle Cell Senescence by Interacting With LncRNA GAS5/SDC1
Chen, T., Liang, Q., Xu, J., Zhang, Y., Zhang, Y., Mo, L., & Zhang, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.700006 · Cited by 28
Beta Cell Therapies for Preventing Type 1 Diabetes: From Bench to Bedside
Brawerman, G. M., & Thompson, P. J. (2020) · Biomolecules · doi:10.3390/biom10121681 · Cited by 29
Endothelial dysfunction in the aging kidney
Borri, M., Jacobs, M. E., Carmeliet, P., Rabelink, T. J., & Dumas, S. J. (2025) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00287.2024 · Cited by 31
Astrocyte-Derived Extracellular Vesicles (ADEVs): Deciphering their Influences in Aging
Rouillard, M. E., Sutter, P. A., Durham, O. R., Willis, C. M., & Crocker, S. J. (2021) · Aging and Disease · doi:10.14336/ad.2021.0608 · Cited by 29
“observed in aging leads to the loss of cellular resistance that renders cells more susceptible to damaging stimuli, such as oxidative stress [78], inflammation [79-81], metabolic dysfunction [82, 83], and the accumulation of”
BackgroundMitochondrial-related microRNAs and their roles in cellular senescence
Luo, L., An, X., Xiao, Y., Sun, X., Li, S., Wang, Y., Sun, W., & Yu, D. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2023.1279548 · Cited by 30
Guo, Y., Chen, T., Liang, X., et al. (2022) · Cells · doi:10.3390/cells11233893 · Cited by 27
“experimentally demonstrated that aminooxyacetic acid can decrease the NAD+/NADH ratio by inhibiting GOT1, leading to cellular senescence [19].”
BackgroundGibbs, E. T., Lerner, C. A., Watson, M. A., Wong, H. S., Gerencser, A. A., & Brand, M. D. (2023) · Biochemical Journal · doi:10.1042/bcj20220611 · Cited by 29
Self-citationGao, P., Zhang, H., Zhang, Q., Xia, F., Wu, H., Wang, M., Lu, Z., Wei, X., Yang, G., Yan, Z., et al. (2019) · Hypertension · doi:10.1161/hypertensionaha.118.12086 · Cited by 28
“In addition, mitochondrial dysfunction-associated senescence also depends on p53 activation.(20) Although active p53 represses expression of PGC-1α (peroxisome proliferator-activated receptor-γ, coactivator 1α), a critical transcription factor contributing to mitochondrial biogenesis thereby reduces oxygen consumption…”
BackgroundThe female reproduction and senescence nexus
Marquez, C. M., Ibana, J. A., & Velarde, M. C. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12646 · Cited by 28
Self-citationCellular Senescence, Inflammation, and Cancer in the Gastrointestinal Tract
Choi, E. L., Taheri, N., Chandra, A., & Hayashi, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24129810 · Cited by 29
“Thus, DNA damage coincides with p53 expression, which is caused by mitochondrial apoptosis [17]; mitochondrial dysfunction, which increases p53 expression in senescent cells [18]; and p53 expression, which inhibits mitochondrial elongation in cell senescence [19].”
BackgroundPremature Senescence and Increased Oxidative Stress in the Thymus of Down Syndrome Patients
Marcovecchio, G. E., Ferrua, F., Fontana, E., Beretta, S., Genua, M., Bortolomai, I., Conti, A., Montin, D., Cascarano, M. T., Bergante, S., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.669893 · Cited by 30
“Increased oxidative stress has been linked to the accumulation of dysfunctional mitochondria (39), which in turn play a relevant role in triggering senescent process (40).”
BackgroundCholesterol biosynthetic pathway induces cellular senescence through ERRα
Ziegler, D. V., Czarnecka‐Herok, J., Vernier, M., Scholtes, C., Camprubi, C., Huna, A., Massemin, A., Griveau, A., Machon, C., Guitton, J., et al. (2024) · npj Aging · doi:10.1038/s41514-023-00128-y · Cited by 33
“Mitochondria is one of the major sites of ROS production in the cell 41 and its dysregulation participates in cellular senescence 13,19,42 .”
BackgroundAutophagy and PTEN in DNA damage-induced senescence
Sharma, A., & Almasan, A. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.01.006 · Cited by 26
Culibrk, R. A., & Hahn, M. S. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.583884 · Cited by 28
“While SASPs surface from a variety of factors, including cell type, mechanism of senescence induction, and hormonal milieu (Wiley et al., 2016), inflammatory cytokines, including IL-6 and IL-8, are highly conserved in SASPs and are believed to play a crucial role in maintaining SASP signaling and senescence (Acosta et…”
BackgroundXiong, Y., Huang, W., Ling, X., Zhou, S. Y., Wang, X., Li, X., & Zhou, L. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01298-5 · Cited by 28
“…DNA/ mtDNA mutation could solely induce premature aging phenotype [18, 19], exhibiting excessive ROS production, abnormal mitochondrial unfolded protein response, decreased mitophagy, accumulation of erroneous proteins, persistent chronic in fl ammation and decreased NAD + /NADH ratio [20, 21].”
Oxaloacetate decarboxylase FAHD1 – a new regulator of mitochondrial function and senescence
Etemad, S., Petit, M., Weiss, A. K. H., Schrattenholz, A. S., Baraldo, G., & Jansen‐Dürr, P. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.07.007 · Cited by 27
Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging
Wong, W., Crane, E. D., Zhang, H., Li, J., Day, T. A., Green, A. E., Menzies, K. J., & Crane, J. D. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101575 · Cited by 27
“However, NAD þ biology is complicated and can be in fl u-enced by external factors such as increased cellular senescence [52,53], chronic in fl ammation [53,54] or changes in the microbiome [55] in conjunction with epidermal genomic damage [42].”
BackgroundTargeting Mitochondria to Control Ageing and Senescence
Protasoni, M., & Serrano, M. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020352 · Cited by 30
“For example, cells that underwent mitochondrial dysfunction-associated senescence are characterised by lower NAD+/NADH ratios, AMPK-mediated p53 activation, and reduced IL-1-associated SASP [14].”
BackgroundInfluentialThe dual role of cellular senescence in human tumor progression and therapy
Ma, L., Yu, J., Fu, Y., He, X., Ge, S., Jia, R., Zhuang, A., Yang, Z. H., & Fan, X. (2024) · MedComm · doi:10.1002/mco2.695 · Cited by 30
Matar, D. B., Elahi, M. A., Sukkarieh, H. H., Nassar, W. K., & Aljada, A. (2025) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2025.120424 · Cited by 27
Progresses in both basic research and clinical trials of NAD+ in Parkinson’s disease
Maria Jose Perez, J., Baden, P., & Deleidi, M. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111499 · Cited by 26
Jiang, X., Xu, Z., Dong, Y., Liu, X., Liu, W., Wang, N., Li, X., Diao, Y., Zhang, Y., & Zhao, Q. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106210 · Cited by 27
Metabolic reprogramming in cancer and senescence
Zhang, Y., Tang, J., Jiang, C., Yi, H., Shu, G., Yin, G., & Wang, M. (2025) · MedComm · doi:10.1002/mco2.70055 · Cited by 25
“In 2016, mitochondrial dysfunction-associated senescence (MiDAS), defined by Wiley et al., 208 was experimentally shown to induce cellular senescence with a unique secretory pattern.”
Understanding and targeting senescence in kidney disease
Chanvillard, L., Mason, T., & Ferenbach, D. A. (2025) · Clinical Kidney Journal · doi:10.1093/ckj/sfaf190 · Cited by 28
“This pro-inflammatory secretome is primarily regulated by NF-κ B [77 ], NOTCH1 [78 ], C/EBP β [79 ], and GATA4 [80 ], and its composition varies depending on the location and previous differentiation status of the target cell and the senescence-inducing stressor [81 ].”
Multi-omics strategies to decode the molecular landscape of cellular senescence
Basilicata, M. G., Sommella, E., Scisciola, L., Tortorella, G., Malavolta, M., Giordani, C., Barbieri, M., Campiglia, P., & Paolisso, G. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102824 · Cited by 28
RETRACTED: Impaired lipid metabolism by age-dependent DNA methylation alterations accelerates aging
Li, X., Wang, J., Wang, L., Feng, G., Li, G., Yu, M., Li, Y., Liu, C., Yuan, X., Zang, G., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1919403117 · Cited by 26
“Mitochondria are the powerhouses of the cell and play a prominent role in producing energy through respiration and regulating cellular metabolism (34, 35).”
BackgroundRetractedHudson, H. R., Sun, X., & Orr, M. E. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00519 · Cited by 28
“Mitochondrial dysfunction in senescent cells often drives the release of pro-in fl ammatory factors collectively termed the senescence-associated secretory phenotype (SASP) [23 – 25].”
Noh, S., Lee, S. J., Lee, T. G., Park, K., & Kim, J. H. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.11.003 · Cited by 25
Ahmad, A., Braden, A. A., Khan, S., Xiao, J., & Khan, M. M. (2024) · Seminars in Immunopathology · doi:10.1007/s00281-024-01016-7 · Cited by 31
“Curiously, mitochondrial dysfunction evokes a distinct hypersecretory phenotype of senescence induction [128].”
Time-resolved proteomic analyses of senescence highlight metabolic rewiring of mitochondria
Kim, J. Y., Atanassov, I., Dethloff, F., Kroczek, L., & Langer, T. (2023) · Life Science Alliance · doi:10.26508/lsa.202302127 · Cited by 24
“On the other hand, a decreased cellular NAD+/NADH ratio upon OXPHOS dysfunction is sufficient to drive cells into senescence but results in a distinct SASP profile lacking proinflammatory IL1 cytokines (16).”
BackgroundSenotherapeutics in Cancer and HIV
Sánchez-Díaz, L., Espinosa-Sánchez, A., Blanco, J. R., & Carnero, A. (2022) · Cells · doi:10.3390/cells11071222 · Cited by 27
“In addition, other types of senescence, such as epigenetically induced and mitochondrial dysfunction-induced senescence, have been described [14].”
BackgroundZois, C. E., Hendriks, A. M., Haider, S. A., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05005-2 · Cited by 24
“It is well known that both IR and senescence also induce dysfunctional and elongated mitochondria [49, 50].”
BackgroundGenetic origins, regulators, and biomarkers of cellular senescence
Torres, G., Salladay-Perez, I. A., Dhingra, A., & Covarrubias, A. J. (2024) · Trends in Genetics · doi:10.1016/j.tig.2024.08.007 · Cited by 24
Wu, H., Sun, C., Cao, W., Teng, Q., Ma, X., Schiöth, H. B., Dong, R., Zhang, Q., & Kong, B. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217192 · Cited by 29
“An increasing body of evidence indicates that mitochondrial dysfunction contributes to the onset of senescence [44 – 46].”
BackgroundWu, W., Yuan, S., Tang, Y., Meng, X., Peng, M., Hu, Z., & Liu, W. (2023) · Nutrients · doi:10.3390/nu15132851 · Cited by 33
“In addition to this, exercise activates AMPK by changing the NAD+/NADH ratio [89].”
BackgroundKurth, F., Tai, Y. K., Parate, D., van Oostrum, M., Schmid, Y. R. F., Toh, S. J., Yap, J. L. Y., Wollscheid, B., Othman, A., Dittrich, P. S., et al. (2020) · Advanced Biosystems · doi:10.1002/adbi.202000146 · Cited by 23
Quake, S. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.03.626516 · Cited by 35
Anti-senescence therapies: a new concept to address cardiovascular disease
Stojanović, S. D., Thum, T., & Bauersachs, J. K. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf030 · Cited by 32
“258 Senescence in vivo likely has multiple concurrent and less delineated senescence triggers.”
dos Santos, M. F., Roxo, C., & Solá, S. (2021) · Antioxidants · doi:10.3390/antiox10071088 · Cited by 25
Devulder, J. V., Baker, J. R., Fenwick, P. S., Odqvist, L., Donnelly, L., & Barnes, P. J. (2025) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2024-0183oc · Cited by 27
Ozdemir, S. A., Faizan, M. I., Kaur, G., Shaikh, S. B., Islam, K. U., & Rahman, I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199687 · Cited by 28
Regulatory Mechanisms of Mitochondrial Function and Cardiac Aging
Lin, R., & Kerkelä, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041359 · Cited by 23
“Short hairpin RNA (shRNA) based deletion of mitochondrial SIRT3 and SIRT5 induces cell senescence and mitochondrial dysfunction [80]; in vivo, genetic forced expression of cardiac Sirt1 in mice displays a dose-dependent effect: at low-to-moderate dose, in aged mice it dampens cardiac hypertrophy, fibrosis and improves…”
BackgroundThe interplay between cell death and senescence in cancer
Shimizu, K., Inuzuka, H., & Tokunaga, F. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.11.001 · Cited by 28
The interaction between cellular senescence and chronic kidney disease as a therapeutic opportunity
Zhao, J.-L., Qiao, X.-H., Mao, J., Liu, F., & Fu, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.974361 · Cited by 24
“Traditionally, cellular senescence has been divided into two types, namely Hayflick-type replicative senescence, characterized by the telomere attrition (Hayflick and Moorhead, 1961), and stressinduced premature senescence (SIPS), caused by various stimuli (von Zglinicki, 2002; Sedelnikova et al., 2004; Wiley et al.,…”
BackgroundLoss of the ubiquitin conjugating enzyme UBE2E3 induces cellular senescence
Plafker, K. S., Zyla, K., Berry, W. L., & Plafker, S. M. (2018) · Redox Biology · doi:10.1016/j.redox.2018.05.008 · Cited by 24
Modulation of Oxidative Stress-Induced Senescence during Non-Alcoholic Fatty Liver Disease
Pedroza-Díaz, J., Arroyave-Ospina, J. C., Salas, S. S., & Moshage, H. J. (2022) · Antioxidants · doi:10.3390/antiox11050975 · Cited by 27
“Specific differences in the secretome are also observed such as the lack of IL-1β-dependent factors, most likely due to the high expression of p53, which might limit the expression of NF-kB-dependent SASP factors [109].”
BackgroundPathogenesis of Warthin’s Tumor: Neoplastic or Non-Neoplastic?
Aoki, R., & Tanaka, T. (2024) · Cancers · doi:10.3390/cancers16050912 · Cited by 24
“Recently, interesting findings showing that (1) “mitochondrial DNA mutations accumulate in human tissues with senescence” [69]; and (2) “mitochondrial dysfunction induces aging” have been reported [70].”
BackgroundApoptotic transition of senescent cells accompanied with mitochondrial hyper-function
Wang, D., Liu, Y., Zhang, R., Zhang, F., Sui, W., Chen, L., Zheng, R., Chen, X., Wen, F., Ouyang, H., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8536 · Cited by 26
“Studies have shown that mitochondrial dysfunction not only induces cellular senescence but also drives organismal aging through mechanisms implicating mitochondrial reactive oxygen species (ROS), AMPK and etc [16–19].”
Nita, M., & Grzybowski, A. E. (2020) · EXCLI journal · doi:10.17179/excli2020-2915 · Cited by 22
“…results not only in shortage of antioxidant defense and increased sensitivity to oxidative stress but it also reduces RPE mitochondrial membrane potential (bioenergetics deficit) (He et al., 2010), and stimulates senescence-associated mitochondrial dysfunction in the RPE cells (Wiley et al., 2016).”
BackgroundThe role of heme in sepsis induced Kupffer cell PANoptosis and senescence
Li, T., Adams, J., Zhu, P., Zhang, T., Tu, F., Gravitte, A., Zhang, X., Liu, L., Casteel, J. L., Yakubenko, V. P., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07637-6 · Cited by 28
“Cellular senescence, characterized by cell cycle arrest and the acquisition of a proin fl ammatory senescence-associated secretory phenotype (SASP) [25, 26], represents another potential mechanism of Kupffer cell dysfunction, impairing their ability to self-renew and effectively respond to infection.”
TRIM15 drives chondrocyte senescence and osteoarthritis progression
Li, Z., Zhang, W., Xiao, W., Hu, J. Z., Hu, X., Liu, H., Lü, J., Shen, S., & Ji, M.-L. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adq1735 · Cited by 26
Li, S., Sun, D., Chen, S., Zhang, S., Gu, Q., Shen, Y., Li, X., Xu, X., Wei, F., & Wang, N. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.1.14 · Cited by 27
Zhang, M., Tang, X., Mao, B., Zhang, Q., Zhao, J., Chen, W., & Cui, S. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c05428 · Cited by 28
Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression
Kyi, P., Hendee, K., Hunyenyiwa, T., Matus, K., Mammoto, T., & Mammoto, A. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.908639 · Cited by 24
Regulation of lung progenitor plasticity and repair by fatty acid oxidation
Angeles-López, Q. D., Rodriguez-Lopez, J., Garcia, P. A., Calyeca, J., Álvarez, D., Bueno, M., Tu, L. N., Salazar-Terreros, M. J., Vanegas-Avendaño, N., Krull, J. E., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.165837 · Cited by 27
“…analysis showed that Cpt1a -KD cells exhibited decreased mitochondrial complex I activity (Figure 7D), concomitant with decreased NAD + (Supple-mental Figure 6D) and a lowered NAD + /NADH ratio (Figure 7E), key characteristics of a mitochondrial dysfunction–associated senescence phenotype (37).”
Xin, Y., Yuan, Z., Wang, J., & Li, S. (2025) · The FASEB Journal · doi:10.1096/fj.202500244rrr · Cited by 28
Dynamic Aging: Channeled Through Microenvironment
Tan, Q., Liang, N., Zhang, X., & Li, J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.702276 · Cited by 25
Li, J., Fang, J., Qin, X., & Gao, L. (2020) · Food & Function · doi:10.1039/d0fo01332c · Cited by 23
Obesity, Senescence, and Senolytics
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2021) · Handbook of Experimental Pharmacology · doi:10.1007/164_2021_555 · Cited by 22
Tu, M., Wei, T., Jia, Y., Wang, Y., & Wu, J. (2022) · Journal of Thoracic Disease · doi:10.21037/jtd-22-886 · Cited by 22
“Dysfunctional mitochondria are less efficient in oxidizing NADH to NAD+, resulting in a lower NAD+/NADH ratio, with the activation of AMPK and p53 leading to a senescent phenotype (35).”
Delineating the heterogeneity of senescence-induced-functional alterations in hepatocytes
Kumar, P., Hassan, M., Tacke, F., & Engelmann, C. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05230-2 · Cited by 25
“The process can be triggered by DNA damage [2], onco-gene activation [3], telomeres shortening [4], mitochondrial dysfunction [5, 6], and oxidative stress [7].”
GRSF1 suppresses cell senescence
Noh, J. H., Kim, K. M., Idda, M. L., Martindale, J. L., Yang, X., Abdelmohsen, K., & Gorospe, M. (2018) · Aging · doi:10.18632/aging.101516 · Cited by 22
“Thus, our findings that GRSF1 prevents SASP-associated IL6 production offer valuable insight into the role of mitochondria in cell senescence and organismal aging [8,21].”
BackgroundYAP/TAZ as Molecular Targets in Skeletal Muscle Atrophy and Osteoporosis
Kwon, Y. (2024) · Aging and Disease · doi:10.14336/ad.2024.0306 · Cited by 23
Liu, S., Li, K., He, Y., Chen, S., Yang, W., Chen, X., Feng, S., Xiong, L., Peng, Y., & Shao, Z. (2024) · Advanced Science · doi:10.1002/advs.202400749 · Cited by 23
Self-citationPurhonen, J., Banerjee, R., Wanne, V., Sipari, N., Mörgelin, M., Fellman, V., & Kallijärvi, J. (2023) · Nature Communications · doi:10.1038/s41467-023-38027-1 · Cited by 24
“In cultured cells, mitochondrialdefects caninduce senescence via NAD + /NADH imbalance 16 .”
Influentialde Lange, P., Lombardi, A., Silvestri, E., Cioffi, F., Giacco, A., Iervolino, S., Petito, G., Senese, R., Lanni, A., & Moreno, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411676 · Cited by 26
“CR induces S RT3 expression [143], and also SIRT1 was r porte to mediate aspects f the CR response [144] by reducing levels of oxidative st ess within the cell [145].”
BackgroundAlhaddad, L., Osipov, A. N., & Leonov, S. V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113577 · Cited by 21
“, increased mass [485]) and function [486], the expression of the pH-restricted (pH 6) [487–489], and an altered chromatin organization known as senescence-associated heterochromatin foci (SAHF) [490] contributing to the silencing of proliferation-promoting genes, including E2F target genes, such as cyclin A [491].”
BackgroundHigd-1a regulates the proliferation of pancreatic cancer cells through a pERK/p27KIP1/pRB pathway
An, H., Ryu, M., Jeong, H. J., Kang, M., Jeon, H.-M., Lee, J., Kim, Y. S., & Lee, H. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.07.007 · Cited by 21
Too big not to fail: emerging evidence for size‐induced senescence
Manohar, S., & Neurohr, G. E. (2023) · FEBS Journal · doi:10.1111/febs.16983 · Cited by 21
“In contrast, mitochondrial dysfunction-associated senescence can induce both p16 as well as p53 [46,68,69].”
BackgroundMeasuring the Senescence-Associated Secretory Phenotype
Karras, A., Λιούλιος, Γ., Kantartzi, K. M., Fylaktou, A., Panagoutsos, S. A., & Stangou, M. J. (2025) · Biomedicines · doi:10.3390/biomedicines13092062 · Cited by 27
“Notably, the researchers discovered that while some proteins were consistently secreted regardless of senescence inducer (e.g., IL-8, MMP-1), others were unique to specific senescence pathways, illustrating the pathway-dependent nature of the SASP [72].”
Zhou, X., Tan, B., Gui, W., Zhou, C., Zhao, H., Lin, X., & Li, H. (2023) · Molecular Medicine · doi:10.1186/s10020-023-00752-0 · Cited by 21
“In (Wiley et al. 2016).”
BackgroundSaleh, T., Khasawneh, A. I., Himsawi, N. M., Abu-Raideh, J. A., Ejeilat, V., Elshazly, A. M., & Gewirtz, D. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415512 · Cited by 21
“Senescent cells often accumulate damaged mitochondria characterized by (i) reduced oxidative potential, (ii) decreased mitochondrial membrane potential, (iii) structural changes, and (iv) build-up in free radicals [93,94].”
BackgroundThe miR-30-5p/TIA-1 axis directs cellular senescence by regulating mitochondrial dynamics
Tak, H., Cha, S., Hong, Y., Jung, M., Ryu, S., Han, S., Jeong, S. M., Kim, W., & Lee, E. K. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06797-1 · Cited by 21
“…decline in TIA-1 levels across various tissues [25, 26], our in silico analysis of multiple gene expression data series (GSE) (GSE38718, GSE181022, and GSE58915) from the NCBI Gene Expression Omnibus (GEO) revealed the downregulation of TIA-1 in aging and cellular senescence models (Fig.”
The fate of mitochondrial respiratory complexes in aging
Salmonowicz, H., & Szczepanowska, K. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.02.008 · Cited by 23
Ionic stress induces fusion of mitochondria to 3-D networks: An electron tomography study
Steiner, P., Luckner, M., Kerschbaum, H., et al. (2018) · Journal of Structural Biology · doi:10.1016/j.jsb.2018.06.010 · Cited by 21
Leeson, H. C., Aguado, J., Gómez‐Inclán, C., Chaggar, H. K., Fard, A. T., Hunter, Z. L., Lavin, M. F., Mackay‐Sim, A., & Wolvetang, E. J. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106562 · Cited by 22
Anastasopoulos, N.-A., Charchanti, A. V., Barbouti, A., Mastoridou, E. M., GOUSSIA, A. C., Karampa, A. D., Christodoulou, D. K., & Glantzounis, G. K. (2023) · Antioxidants · doi:10.3390/antiox12061269 · Cited by 22
“showed a distinct mitochondrial dysfunction associated with CS phenotype that is activated through a NAD–AMPK–p53 pathway and results in SASP production without IL-1, implicating mitochondrial sirtuins as culprits in this event sequelae [97].”
BackgroundCellular senescence in aging: Molecular basis, implications and therapeutic interventions
Princilly, J., Veerabhadrappa, B., Rao, N. N., & Dyavaiah, M. (2023) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2023.02.021 · Cited by 24
Causes of Pulmonary Fibrosis in the Elderly
Ramírez, C. L., Suárez-Valdivia, L., & Portal, J. A. R. (2018) · Medical Sciences · doi:10.3390/medsci6030058 · Cited by 25
“It has been shown that mitochondrial dysfunction induced by mtDNA depletion induces senescence with a distinct phenotype, termed MiDAS (mitochondrial dysfunction-associated senescence) [65].”
BackgroundAn Analysis of Metabolic Changes in the Retina and Retinal Pigment Epithelium of Aging Mice
Tsantilas, K. A., Cleghorn, W. M., Bisbach, C. M., Whitson, J. D., Hass, D. T., Robbings, B. M., Sadı́lek, M., Linton, J. D., Rountree, A. M., Valencia, A. P., et al. (2021) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.62.14.20 · Cited by 22
P53: A Key Target in the Development of Osteoarthritis
Ma, W., Tan, X., Xie, Z., Jiang, Y., Li, P., Lin, X., Ouyang, S., Liu, Z., Hou, Q., Xie, N., et al. (2023) · Molecular Biotechnology · doi:10.1007/s12033-023-00736-9 · Cited by 20
“Previous studies have demonstrated that p53 not only has elevated expression in aged cartilage [23], but also plays a key role in modulating chondrocyte apoptosis [24, 25], senescence [26, 27] and autophagy [28], all of which are typical pathological changes in OA.”
Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice
(2020) · doi:10.1101/2020.01.02.893008 · Cited by 20
“Compared to old controls, SS-31 treated hearts have reduced numbers of p16- or p19-positive senescent cells and this may be a direct result of the restoration of mitochondrial function (Wiley et al., 2016).”
BackgroundInfluentialPropagation of senescent phenotypes by extracellular HMGB1 is dependent on its redox state
Shin, J.-W., Jang, D., Kim, S. Y., Lee, J., Gil, T., Shim, E., Kim, J. Y., Kim, H. S., Conboy, M. J., Conboy, I. M., et al. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156259 · Cited by 21
Self-citationPreventing MSC aging and enhancing immunomodulation: Novel strategies for cell-based therapies
Elmi, F., Soltanmohammadi, F., Arjmand, T. F., Farajnia, S., & Alizadeh, E. (2025) · Regenerative Therapy · doi:10.1016/j.reth.2025.04.014 · Cited by 22
“Abnormalities in the respiratory chain, such as an imbalance between ATP þ ADP and NAD þ NADH ratios that are associated with MSC senescence, have been shownto becausedby malfunctioning mitochondria[93].”
The Role of Senescence-Associated Secretory Phenotype in Bone Loss
Zhu, R., Wan, H., Yang, H. S., Song, M., Chai, Y., & Yu, B. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.841612 · Cited by 21
Metadata
- Authors
- Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Freund, A., Shirakawa, K., Lim, H. W., Davis, S. S., Ramanathan, A., Gerencser, A. A., Verdin, E., & Campisi, J.
- Affiliations
- Buck Institute for Research on Aging (US)
- Gladstone Institutes (US)
- Corresponding author
- Campisi, Judith
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 23
- Issue
- 2
- Pages
- 303-314
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4749409
- OpenAlex
- W2191745121
- Cited by
- 1,275
- References
- 66
- Citations by year
- 2026: 162 · 2025: 161 · 2024: 169 · 2023: 148 · 2022: 128 · 2021: 139 · 2020: 115 · 2019: 95 · 2018: 71 · 2017: 51 · 2016: 35
- FWCI
- 38.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (R37AG009909, K99AG041221, T32AG000266)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK085610, P30DK063720, P30DK026743)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial dysfunction, cellular senescence, senescence-associated secretory phenotype, NAD+/NADH ratio, AMPK, p53 activation, progeroid mice, mitochondrial DNA mutations, adipogenesis, keratinocyte differentiation, aging, growth arrest
- MeSH terms
- DNA Polymerase gamma, Adenylate Kinase, Animals, DNA-Directed DNA Polymerase, Enzyme Activation, Mitochondria, NAD, Phenotype, Tumor Suppressor Protein p53, Cellular Senescence, Sirtuins, Mice
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