The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index; 9 of the 19 sources its claims cite were checked for support.
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Open accessAbstract
Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a)-positive senescent cells upon drug treatment. In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
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TL;DR
The paper describes INK-ATTAC, a transgenic mouse system that allows drug-inducible removal of p16Ink4a-positive senescent cells. In a BubR1 hypomorphic progeroid background, clearing these cells delayed or slowed several age-related phenotypes in adipose tissue, skeletal muscle, and eye, supporting a causal role for cellular senescence in age-related dysfunction.
Key findings
- INK-ATTAC expression overlapped with endogenous p16Ink4a: GFP+ cells from aged BubR1H/H;INK-ATTAC adipose tissue had higher p16Ink4a and other senescence markers than GFP− cells, and AP20187 killed most rosiglitazone-induced senescent bone marrow cells within 48 h in vitro.
- Life-long AP20187 treatment from 3 weeks of age in BubR1H/H;INK-ATTAC lines 3 and 5 delayed lordokyphosis and cataracts, increased muscle fibre diameter, improved treadmill exercise duration/distance/work, and prevented adipose tissue loss; these delays were absent in BubR1H/H mice without the transgene.
- Late-life treatment starting at 5 months and assessed at 10 months improved muscle fibre size and exercise performance and increased fat depots and adipocyte size, but cataracts that had already matured remained unchanged; the effects reflected slowed progression rather than reversal of ageing.
- p16Ink4a-independent phenotypes such as cardiac arrhythmias and arterial wall stiffening were not attenuated, and overall survival was not substantially extended, likely because cardiac failure is the main cause of death in this model. No overt side effects were observed in WT;INK-ATTAC mice treated until 8 months.
Methods
- The INK-ATTAC construct used a 2,617-bp murine p16Ink4a promoter fragment to drive FKBP–Casp8, with an IRES-EGFP reporter; nine transgenic founder lines were generated and bred onto the BubR1 hypomorphic background, with lines 3 and 5 selected for study.
- AP20187 was injected intraperitoneally every 3 days at 0.2 μg/g body weight from weaning (life-long) or from 5 months (late-life); phenotypes were assessed by lordokyphosis and cataract checks, muscle and fat histology, DEXA, treadmill exercise, BrdU incorporation, SA-β-Gal staining, qRT–PCR, and FACS.
- In vitro, bone marrow cells were treated with 1 μM rosiglitazone for 5 days and then 10 nM AP20187 for 48 h; MEFs were induced to senesce by serial passaging (12–15 passages) or H-ras expression, sorted into GFP+ and GFP− populations, and analysed. Statistical comparisons used two-tailed unpaired t tests and log-rank tests.
Limitations
- The paper states that no universal marker expressed solely in senescent cells has been identified, and the approach relies on p16Ink4a promoter activity and two transgenic lines.
- The paper notes that overall survival was not substantially extended, probably because cardiac failure dominates mortality in BubR1H/H mice; p16Ink4a-independent pathologies were unaffected, and mature cataracts did not improve with late-life clearance.
- Evident from the text: the findings are in a progeroid BubR1 hypomorphic mouse model rather than natural ageing, some measurements were performed in female mice, and absence of overt side effects was only tested in WT;INK-ATTAC mice up to 8 months.
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Claims the paper makes
31 Own result · 7 No full text of the sources · 4 Partly supported · 4 Own interpretation · 3 Supported · 2 No basis given · 1 Supported so far · accuracy not yet measured
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
“Although a universal marker that is solely expressed in senescent cells has not been identified, most senescent cells seem to express p16Ink4a, a cyclin-dependent kinase inhibitor and tumour suppressor that enforces growth arrest by activating Rb5,7.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Supportedcites [5] Rodier, F. & Campisi, J. Four faces of cellular senescence. J. Cell Biol. 192, 547–556 (2011) source
In “What defines a senescent cell?” the paper explicitly states that most senescent cells express p16INK4a. The same section notes that no identified marker is entirely specific to senescence, consistent with the citing sentence’s qualification. (LLM, conf=0.95)
- Not checked — no full text of the sourcecites [7] Kim, W. Y. & Sharpless, N. E. The regulation of INK4/ARF in cancer and aging. Cell 127, 265–275 (2006) source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Furthermore, our data indicate that acquisition of the senescence-associated secretory phenotype (SASP), which enables cells to secrete a variety of growth factors, cytokines and proteases4, contributes to age-related tissue dysfunction.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Supportedcites [4] Coppé, J. P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, e301 (2008) source
The citation is attached to the description of the SASP, not to the citing authors’ conclusion about age-related tissue dysfunction. The source paper’s Discussion describes the SASP as a secretory phenotype and reports high levels of secreted inflammatory cytokines and growth factors; it also suggests that chronic secretion may disrupt tissue function. (LLM, conf=0.87)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“rosiglitazone, a drug that can induce cellular senescence and p16Ink4a expression through activation of PPARγ16.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Partly supportedcites [16] Gan, Q. et al. PPARγ accelerates cellular senescence by inducing p16INK4α expression in human diploid fibroblasts. J. Cell Sci. 121, 2235–2245 (2008) sourceExperimental — accuracy not yet measured
The “PPARγ-mediated regulation of p16INK4α expression” section reports that PPARγ overexpression or troglitazone treatment increased p16 protein in human fibroblasts; the RNA-interference section links PPARγ-agonist effects to senescence. The paper’s treatment passages name troglitazone and pioglitazone, not rosiglitazone, so they do not establish the claim for that specific drug. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Senescent cells accumulate in various tissues and organs with ageing3”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Supportedcites [3] Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513–522 (2005) source
In the “Cellular Senescence and Aging” passage, the paper states that cells with characteristics of senescence accumulate with age in multiple tissues in humans and rodents. This supports the citing sentence’s claim. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“We replaced the Fabp4 promoter with a 2,617-bp fragment of the p16Ink4a gene promoter that is transcriptionally active in senescent, but not non-senescent cells (Fig. 1a)9.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Partly supportedcites [9] Wang, W., Wu, J., Zhang, Z. & Tong, T. Characterization of regulatory elements on the promoter region of p16INK4a that contribute to overexpression of p16 in senescent fibroblasts. J. Biol. Chem. 276, 48655–48661 (2001) sourceExperimental — accuracy not yet measured
The Discussion reports that the tested p16INK4a promoter fragments were 5–7 times more active in senescent than in young fibroblasts, supporting senescence-associated activity. It does not identify a 2,617-bp fragment, and its measurements of promoter activity in young cells do not support the claim that the promoter is inactive in non-senescent cells. (LLM, conf=0.84)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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
“Skeletal muscle and eye had a similar reduction in senescence indicators (Fig. 3c, d and Supplementary Fig. 6b, c).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Age-related phenotypes of BubR1H/H mice that arise in a p16Ink4a-independent fashion, such as cardiac arrhythmias and arterial wall stiffening14, were not attenuated in AP20187-treated BubR1H/H;INK-ATTAC mice (Supplementary Fig. 5a, b).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Not checked — no full text of the sourcecites [14] Matsumoto, T. et al. Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke 38, 1050–1056 (2007) source
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
“The above age-related phenotypes were not delayed upon AP20187 treatment of BubR1H/H mice lacking INK-ATTAC (Fig. 2b and Supplementary Fig. 4).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that the vast majority of cells from both transgenic lines were either dead or in the process of dying 48 h after adding AP20187 (Fig. 2a).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
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 IAT of AP20187-treated BubR1H/H;INK-ATTAC mice showed a marked decrease in SA-β-Gal staining compared with the IAT of untreated counterparts (Fig. 3a).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 4
- It may state two separate claims as one. 8
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Additionally, the expression of p16Ink4a is known to increase with ageing in several rodent and human tissues8.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Partly supportedcites [8] Krishnamurthy, J. et al. Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 114, 1299–1307 (2004) sourceExperimental — accuracy not yet measured
The 'Expression of Ink4a/Arf in vivo' section reports increased p16INK4a expression with age across many mouse and rat tissues. Table 1 compares those findings with published human tissue staining, but does not show age-related increases across several human tissues; the References name evidence for aging human kidney specifically. The claim's extension to several human tissues is therefore not established by this copy (no page numbers available). (LLM, conf=0.86)
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
“senescence-associated secretory phenotype (SASP), which enables cells to secrete a variety of growth factors, cytokines and proteases4”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Partly supportedcites [4] Coppé, J. P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, e301 (2008) sourceExperimental — accuracy not yet measured
In the Results section on senescent fibroblasts (page unavailable), the paper identifies cytokines and growth factors as SASP components and reports increased secretion of SASP proteins. The passages in our copy do not identify secreted proteases as SASP components, so that part of the claim is unsupported. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells1,2.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Supportedcites [1] Campisi, J. Cellular senescence: putting the paradoxes in perspective. Curr. Opin. Genet. Dev. 21, 107–112 (2011) source
In “Senescent cells – in culture and in vivo,” the paper describes an essentially irreversible growth arrest in response to stresses including DNA damage and dysfunctional telomeres. In “Cellular senescence and tumor suppression,” it says that this growth arrest suppresses malignant tumorigenesis and that dismantling the senescence response accelerates progression from premalignant lesions to malignant tumors. (LLM, conf=0.93)
- Supportedcites [2] Kuilman, T., Michaloglou, C., Mooi, W. J. & Peeper, D. S. The essence of senescence. Genes Dev. 24, 2463–2479 (2010) source
In “Replicative cellular senescence,” the paper says that sufficiently severe DNA damage can lead to senescence rather than continued proliferation. “Cellular senescence as a pathophysiological phenomenon” describes oncogene-induced proliferation arrest as a defense against tumor formation, and “Secreted factors in senescence” says senescence limits the expansion of early malignant cells. Page numbers are not available in our copy. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- 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
“Importantly, late-life treated animals had increased mean muscle fibre diameters and showed improved performance in treadmill exercise tests (Fig. 4a, b).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
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
“Together, these data indicate that senescent cells were cleared from tissues and that this delays acquisition of age-related dysfunction in BubR1 hypomorphic mice.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
hedgeddirect- 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
“Furthermore, most fat depots of these animals were enlarged and adipocyte cell size and subdermal adipose layer thickness were significantly increased (Fig. 4c–e).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
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
“treadmill exercise tests revealed that duration of exercise, distance travelled and overall amount of work performed were all significantly increased in the animals treated with AP20187 (Fig. 2e), indicating preservation of muscle function.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
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
“We observed GFP fluorescence in two of these strains, BubR1H/H;INK-ATTAC-3 and -5 (Fig. 1b and Supplementary Fig. 1a).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Skeletal muscle and lens tissue of aged BubR1H/H;INK-ATTAC mice are SA-β-Gal negative (data not shown), but both these tissues expressed other markers of senescence (Fig. 1f and Supplementary Fig. 3a).”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“AP20187, a synthetic drug that induces dimerization of a membrane-bound myristoylated FK506-binding-protein–caspase 8 (FKBP–Casp8) fusion protein expressed specifically in adipocytes via the minimal Fabp4 promoter6.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Not checked — no full text of the sourcecites [6] Pajvani, U. B. et al. Fat apoptosis through targeted activation of caspase 8: a new mouse model of inducible and reversible lipoatrophy. Nature Med. 11, 797–803 (2005) source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“BubR1H/H mice have a markedly shortened lifespan and exhibit a variety of age-related phenotypes, including infertility, lordokyphosis, sarcopenia, cataracts, fat loss, cardiac arrhythmias, arterial wall stiffening, impaired wound healing and dermal thinning12–14.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
What the sources say
- Not checked — no full text of the sourcecites [12] Baker, D. J. et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nature Genet. 36, 744–749 (2004) source
- Not checked — no full text of the sourcecites [13] Hartman, T. K., Wengenack, T. M., Poduslo, J. F. & van Deursen, J. M. Mutant mice with small amounts of BubR1 display accelerated age-related gliosis. Neurobiol. Aging 28, 921–927 (2007) source
- Not checked — no full text of the sourcecites [14] Matsumoto, T. et al. Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke 38, 1050–1056 (2007) source
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.
The authors state this as an assumption.
Cardiac failure is the main cause of death in BubR1H/H mice.
“Cardiac failure is presumably the main cause of death in BubR1H/H mice (data not shown)”
The paper relies on this without support.
Before this study, it was unknown whether senescent cells are causally implicated in age-related dysfunction and whether removing them is beneficial.
“However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown.”
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 cited source doesn’t support the claim as written.
In the citing paper
“Reducing highly p16Ink4a+-expressing cells, some of which are senescent, in INK-ATTAC transgenic mice starting from mid-adulthood (age 12 months) reportedly extends median lifespan49.”
From Senolytics improve physical function and increase lifespan in old age (2018) · cites this paper as [49]
Checked by a reasoning model — may be wrong.
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
“Ablating p16+ cells in these mice suppresses age-related disease, extending the health span of two independent strains of transgenic mice: INK-ATTAC and p16-3MR (see Supplemental Figure 1 for a description of the models) (8–10).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [8]
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
“This BubR1H/H progeria model has accelerated and elevated superphysiologic levels of cellular senescence due to chromosome missegregation as well as increasing aneuploidy (8, 80).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [8]
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
“In addition, many immune cell types and subtypes develop a senescence-like state with increased expression of p16, p21, and SASP factors92,93.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [93]
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
“Interestingly, adaptive immune function can be improved by short-term treatment with rapamycin95, which reduces the markers of senescence and SASP in PBMCs93.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [93]
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
“The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene.”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Baker et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both recent intervention studies18 and our correlative data presented here strongly underscore the importance of cell senescence for determination of ageing rate and lifespan in mammals.”
From Chronic inflammation induces telomere dysfunction and accelerates ageing in mice (2014) · cites this paper as [18]
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
“A cohort of aged INK-ATTAC transgenic mice, in which cells with high INK4a promoter activity, which is indicative of senescence, can be forced to undergo apoptosis138,139, exhibited increased resilience to pathogens, including the mouse hepatitis virus (MHV, a mouse β-coronavirus), when p16INK4a-high senescent cells were subjected to ATTAC-dependent depletion27.”
From COVID-19 and cellular senescence (2023) · cites this paper as [138]
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
“In pre-clinical aging models, accumulation of senescent cells is associated with multiple chronic diseases and disorders, geriatric syndromes, multi-morbidity, and accelerated aging phenotypes.”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Elimination of even a relatively small proportion of existing senescent cells (~30% reduction) using a “suicide” transgene, INK-ATTAC, that permits inducible elimination of p16Ink4a-expressing senescent cells upon administration of a drug (AP20187; Figure 2), extends healthspan and prevents the development of multiple age-related morbidities in both progeroid and normal chronologically-aged mice [”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“mice that express low levels of the spindle assembly checkpoint protein BubR1 (BubR1H/H) exhibit multiple age-related phenotypes at 3–5 months of age, including atrophic skeletal muscle fibers, muscle wasting, and impaired skeletal muscle regeneration”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Baker et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Compared to vehicle-treated mice, skeletal muscle of life-long AP20187-treated mice exhibited significantly lower expression of transgene elements (CASP8, EGFP) and senescence markers, including p16, p21, p19, Pai1, Il6, Mmp3, and Mmp13.”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Baker et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Transgenic mouse lines where senescent cells can be cleared by a genetic construct and commercially available senolytic drugs should also be considered as sensitivity to senolytic methods is one of the strongest lines of evidence currently used in the literature [167,172–174].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [172]
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
“Importantly, genetic or chemical ablation of senescent cells in mouse models delays the onset of age-related disorders, including cancer, leading to increased life-spans and promoting tissue rejuvenation in late life.36–38”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [37]
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
“depletion of cells expressing the senescence marker cyclin-dependent kinase inhibitor p16INK4A in genetically modified mice prolongs median lifespan and improves overall health (Baker et al. 2016; Farr et al. 2017; Baker et al. 2011; Jeon et al. 2017; Abdul-Aziz et al. 2019; Kim et al. 2019; Patil et al. 2019; Xu et al. 2015; Roos et al. 2016; Baar et al. 2017)”
From Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain (2020) · cites this paper as Baker et al. 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Treatments to target and kill senescent cells, like senolytics, have shown promising results in extending lifespans and ameliorating various diseases.12,13”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [13]
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
“mutant mice with premature aging due to extensive and persistent damage, present dramatic levels of senescence and their progeroid phenotypes are ameliorated by elimination of p16Ink4a or p53”
From The Hallmarks of Aging (2013) · cites this paper as Baker et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Removal of the p16Ink4a-positive senescent cells, for instance, using a suicide gene under the regulation of the Cdkn2a promoter has been shown to attenuate progression of age-related decline and preserve cognitive function in both an accelerated aging AD mouse model and a tauopathy mouse model (Baker et al., 2011; Bussian et al., 2018).”
From Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer’s model (2022) · cites this paper as Baker et al., 2011
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Consistent with this idea is the observation that interference with senescent cell accumulation in BubR1 progeroid mice delays several aging-associated disorders that these animals develop 4 , 5 .”
From Naturally occurring p16Ink4a-positive cells shorten healthy lifespan (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Although drug-treated BubR1H/H;INK-ATTAC mice did not live longer, they were remarkably protected from several other age-related pathologies, including cataracts, sarcopenia, and loss of subcutaneous fat (128).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [128]
The cited source says what the claim attributes to it.
In the citing paper
“This study provided the first direct evidence that senescent cells can, at least in a premature aging mouse model, drive degenerative age-related pathology.”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [128]
The cited source says what the claim attributes to it.
In the citing paper
“The idea that senescent cells can drive age-related pathology recently received substantial support from a transgenic mouse model in which senescent cells could be eliminated by administering a drug (128).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [128]
The cited source says what the claim attributes to it.
In the citing paper
“treatment of BubR1 hypomorphic mice harbouring the INK-ATTAC transgene to remove p16-expressing cells beginning at weaning age attenuated the accumulation of senescent cells and premature ageing in skeletal muscle, eye and adipose tissue11”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“Removal of SnCs delays several pathologies7–9 and increases healthy lifespan8.”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“the previously reported INK-ATTAC transgenic mouse model, which expresses the FK506 binding protein–caspase-8 fusion protein under the control of the p16INK4a promoter7,8.”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Earlier we have shown that, in BubR1 progeroid mice, ATTAC ablates p16 Ink4a -positive senescent cells upon administration of AP20187 (AP), a dimerizer that activates FKBP-fused Casp8 4 .”
From Naturally occurring p16Ink4a-positive cells shorten healthy lifespan (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Selective removal of p16 INK4A+ cells from BubR1 H/H INK-ATTAC mice delays kyphosis, cataracts, and muscle atrophy”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Baker et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“but it does not delay cardiac arrhythmias and arterial wall stiffening nor does it extend lifespan”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Baker et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“the demonstration that ablation of p16 INK4A expressing cells slowed age-related declines in progeroid BubR1 H/H mice”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Baker et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“provided the first evidence that senescent cells are causal for certain aging phenotypes”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Baker et al., 2011
The cited source says what the claim attributes to it.
In the citing paper
“Models of accelerated cellular senescence show premature ageing and increased incidence of age-related pathologies, suggesting that accumulating senescent cells contributes to ageing-related functional compromise and predisposes to age-related disease [38].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
The cited source says what the claim attributes to it.
In the citing paper
“However, senescence has also been implicated both in promoting carcinogenesis 15 and in age-related pathologies 16,17 through its autocrine and paracrine effects, known as the senescence-associated secretory phenotype (SASP) originally described by the Campisi group.18,19”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“Using the Ink-Attac mouse model, in which a drug, AP20187 (AP), induces apoptosis through dimerization of FKBP-fused caspase 8, we previously discovered that clearance of p16-expressing cells improves parameters of physical health and function in progeroid mice31.”
From Cellular senescence mediates fibrotic pulmonary disease (2017) · cites this paper as [31]
The cited source says what the claim attributes to it.
In the citing paper
“Clearance of senescent cells is also beneficial for age-associated disorders 39 .”
From A complex secretory program orchestrated by the inflammasome controls paracrine senescence (2013) · cites this paper as [39]
The cited source says what the claim attributes to it.
In the citing paper
“elimination of senescent cells in an experimental progeria model delays age-related pathologies”
From The Hallmarks of Aging (2013) · cites this paper as Baker et al., 2011
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Longer term treatments (from 20 to 26 months of age) were effective at opposing several known phenotypes of aging: macrophage infiltration of tissues, a hallmark of chronic inflammation23,25, glomerulosclerosis of the kidney26 and skeletal muscle atrophy27 (Fig. 4e).”
From L1 drives IFN in senescent cells and promotes age-associated inflammation (2019) · cites this paper as [27]
Experimental — accuracy not yet measuredIn the citing paper
“Seminal discoveries, first by Hayflick and Moorehead, and lately by Baker et al., concretized cellular senescence as a major driver of aging with the age-associated accumulation of senescent cells”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Baker et al. 2011
In the citing paper
“and attenuation of age-related tissue dysfunction after their removal, even late in life (Hayflick and Moorhead 1961, Baker et al. 2011).”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Baker et al. 2011
In the citing paper
“Of note, we and our colleagues recently identified a possibly causal link between cellular senescence and aging phenotypes by showing that the clearance of senescent cells in a mouse progeroid model in vivo can delay age-related tissue dysfunction, including cataract formation, lipodystrophy, and lordokyphosis (7).”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“Experiments in progeroid INK-ATTAC;BubR1H/H mice showed that senescent cell clearance could reverse age-related lipodystrophy.”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“Current methods for assessing senescent cell burden in vivo are at the tissue level, either by quantification of senescent cells through methods such as immunohistochemistry for markers including heterochromatin foci, p16 expression, SA-βgal activity, or screening for transgenic labels such as the p16INK4A promoter-driven GFP in the INK-ATTAC mouse (7).”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“The development of transgenic mice from which senescent cells can be selectively cleared allowed the demonstration of senescent cells' causal role in disease (7).”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“Removal of senescent cells can attenuate age-related tissue dysfunction and extend health span.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Baker et al., 2011
In the citing paper
“selective elimination of senescent cells can prevent or delay age-related tissue dysfunction to extend life span and improve health span (Baker et al., 2011; Xu et al., 2015a; Baker et al., 2016; Hashimoto et al., 2016; Zhao et al., 2018).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Baker et al., 2011
In the citing paper
“Recently, attention has focused on the effect of senescence in vivo where purging p16-positive senescent cells in transgenic mice increased mean lifespan as well as aspects of healthspan65.”
From The central role of DNA damage in the ageing process (2021) · cites this paper as [65]
In the citing paper
“Another key feature of cellular senescence is the senescence-associated secretory phenotype (SASP), which is dependent on p38MAPK (p38 mitogen-activated protein kinases), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), cGAS(cyclic GMP-AMP synthase)/STING(stimulator of IFN genes), NOTCH and mTORmammalian target of rapamycin) signalling [38,39,40,41,42].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“Models of accelerated cellular senescence show premature ageing and increased incidence of age-related pathologies, suggesting that accumulating senescent cells contributes to ageing-related functional compromise and predisposes to age-related disease [38].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“Increased levels of p16INK4a have been documented in aged and stressed tissues, compared to younger, healthy tissues, whereas the removal of p16INK4a-expressing senescent cells in mice prevented or delayed tissue dysfunction and age-related disorders [38,80].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“progeroid models have provided in vivo experimental data of accelerated ageing-related degenerative pathologies.”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“In addition, experimental senolysis ameliorated ageing-related pathologies [38].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“Lifelong elimination of p16INK4A cells substantially delayed age-related disease, whereas late life elimination of p16INK4A cells attenuated these age-related pathologies [38]”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“robust in vivo proof of the causative involvement of senescent cells in aging and in particular age-related diseases10,11.”
From Identification and characterization of Cardiac Glycosides as senolytic compounds (2019) · cites this paper as [11]
In the citing paper
“clearing senescent cells from progeroid or naturally aging mice improves healthspan 10, increases lifespan 12 and benefits an array of pathologies”
From Cardiac glycosides are broad-spectrum senolytics (2019) · cites this paper as [10]
In the citing paper
“Genetic and pharmacological strategies have demonstrated the benefits of eliminating senescent cells in the context of aging and disease 10,12,51.”
From Cardiac glycosides are broad-spectrum senolytics (2019) · cites this paper as [10]
In the citing paper
“To circumvent this problem, two similar yet unique mouse models have been developed to detect and eliminate senescent cells.”
From Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives (2018) · cites this paper as [29]
In the citing paper
“Using mouse models, elimination of these cells, through either genetic means or senolytic therapies, has largely shown beneficial impacts, irrespective of the disease or condition investigated (29-31, 99, 100).”
From Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives (2018) · cites this paper as [29]
In the citing paper
“In mice, the clearance of p16INK4A-positive cells extends lifespan and slows the emergence of ageing phenotypes and age-related functional deterioration of organs and tissues111,112.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [111]
In the citing paper
“It is thus not surprising that senescent cell burden is a good predictor of animal lifespan.94,95”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [94]
In the citing paper
“the clearance of senescent cells by either genetic engineering or the administration of senolytic drugs has been associated with reduced circulating levels of pro-inflammatory markers, increased lifespan, and delayed frailty-related phenotypes in mice”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [111]
In the citing paper
“Elimination of senescent cells by suicide gene-mediated ablation of p16Ink4a-expressing senescent cells in INK-ATTAC mice has resulted in significant improvements in healthspan and lifespan”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Baker et al., 2011
In the citing paper
“suggesting that senescent cells are drivers of ageing (Baker et al., 2011, Baker et al., 2016).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Baker et al., 2011
In the citing paper
“Elimination of senescent cells may therefore allow better recovery of tissues, consistent with the finding that senescent cell elimination via transgenic techniques improves aging‐associated phenotypes”
From p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling (2017) · cites this paper as Baker et al, 2011
In the citing paper
“INK-ATTAC mice can be used as a reporter to track the dynamics of p16Ink4a-positive cells.”
From Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence (2024) · cites this paper as [25]
In the citing paper
“Indeed, sub-populations of senescent MuSCs marked by expression of p16Ink4a contribute to sarcopenic wasting and repair dysfunction characteristic of aged muscles in the accelerated-aging BubR1 hypomorphic mouse model59,60.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [60]
In the citing paper
“Conditional ablation of this p16Ink4a-expressing MuSC population and other senescent cells ameliorates muscle wasting, leading to improved performance in treadmill exercise tests60.”
From The central role of muscle stem cells in regenerative failure with aging (2015) · cites this paper as [60]
In the citing paper
“In animals, genetic and pharmacologic reduction of senescent cell burden results in the prevention, delay, and/or alleviation of a variety of aging-related diseases and sequelae.”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [3]
In the citing paper
“Senolytics have been used to prevent, delay, or alleviate a plethora of age-onset diseases and syndromes in pre-clinical models.”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [3]
In the citing paper
“While genetic models of senescent cell clearance provide proof-of-principle for the health and life span benefits of reducing the burden of old cells and the SASP”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [3]
In the citing paper
“Clearance of senescent cells only late in life did not improve age-related pathologies but did attenuate their progression170.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [170]
In the citing paper
“Using an inducible genetic model for senescent cell ablation, one study demonstrated that life-long clearance of senescent cells from progeroid mouse tissues, via ablation of p16Ink4a-expressing cells, delays the onset of pathologies in multiple aging tissues, including the fat, muscle and eye170.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [170]
In the citing paper
“selective killing of those p16-expressing cells in a premature ageing mouse model also delays ageing phenotypes 148”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [148]
In the citing paper
“Accordingly, removal of senescent cells by genetic or pharmacological “senolytic” approaches extends median lifespan in old mice and prevents the onset of age-associated disease (Baker et al., 2016; Baker et al., 2011; Xu et al., 2018; Zhu et al., 2015).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Baker et al., 2011
In the citing paper
“In support of this tenet, the genetic ablation of p16 + cells in a transgenic mouse model is sufficient to extend the lifespan of naturally aged mice and reduce the manifestation of age-associated pathologies, including cancer.177”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [177]
In the citing paper
“The whole-body elimination of p16 + senescent cells in middle-aged mice reduces the rate of spontaneous tumor formation.177”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [177]
In the citing paper
“The expression of p16Ink4a is essentially undetectable in young and healthy tissues, but p16Ink4a+ cells accumulate in many aged or diseased tissues.18,19,21,22,23,28”
From Identifying specific functional roles for senescence across cell types (2024) · cites this paper as [22]
In the citing paper
“The expression of p16Ink4a is essentially undetectable in young and healthy tissues, but p16Ink4a+ cells accumulate in many aged or diseased tissues.18,19,21,22,23,28”
From Identifying specific functional roles for senescence across cell types (2024) · cites this paper as [22]
In the citing paper
“Moreover, multiple p16-based mouse models [15,26–28] might not target the same p16high cells in vivo due to different transgene designs (such as different p16 promoters or transgene locations).”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [15]
In the citing paper
“Excessive accumulation of senescent cells in numerous tissues leads to multiple chronic diseases, tissue dysfunction, age-related diseases and organ ageing.”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [13]
In the citing paper
“However, excessive accumulation of senescent cells causally shortens the healthy lifespan [11] and drives organ ageing [12], age-related organ deterioration/disorders [13,14], tissue dysfunction and chronic diseases, including cardiovascular diseases (CVDs) [15,16], cancer [2], neurodegenerative diseases [17,18] and osteoarthritis [19].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [13]
In the citing paper
“Exposure to the drug AP20187 causes the caspase 8 fusion protein unique to p16INK4a-expressing cells to dimerize and initiate apoptosis (Baker et al., 2011; Xu et al., 2018).”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Baker et al., 2011
In the citing paper
“Encouragingly, initiation of p16INK4a-postive cell clearance in mid-life also benefitted the molecular and morphological phenotype of skeletal muscle and measures of physical function in progeroid mice.”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Baker et al., 2011
In the citing paper
“Further, muscle fiber size and treadmill exercise time, distance, and total work to exhaustion were significantly greater in AP20187 treated BubR1 H/H;INK-ATTAC mice.”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Baker et al., 2011
In the citing paper
“This model has enabled the study of how systemic removal of p16Ink4a-expressing cells, that are presumably senescent, affect the structure and function of multiple organ systems.”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Baker et al., 2011
In the citing paper
“A major conceptual advance in the role of senescent cells in organismal aging was driven by the development and application of the INK-ATTAC mouse model (Baker et al., 2011).”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Baker et al., 2011
In the citing paper
“In contrast, deletion of senescent cells by a genetic approach attenuated age-related deterioration and extended the health-span in aged mice.8,9”
From Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice (2020) · cites this paper as [8]
In the citing paper
“Senescent cells can impair tissue function in ageing despite their relatively low abundance (< 15%) [3], [4].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [4]
In the citing paper
“Indeed, when senescent cells were removed from aged mice artificially, the animals lived longer and were healthier [96].”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [96]
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“Preclinical studies have found that the development of post-traumatic OA is delayed after local clearance of senescent cells in the articular cartilage of p16-M3R transgenic mice [14], and anti-senescence drugs (i.e., senolytics) also show potential in OA treatment [15–17].”
BackgroundCardiovascular aging: from cellular and molecular changes to therapeutic interventions
Vakka, A., Warren, J. S., & Drosatos, K. (2023) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.09 · Cited by 44
James, E. L., Lane, J. A. E., Michalek, R. D., Karoly, E. D., & Parkinson, E. K. (2016) · Scientific Reports · doi:10.1038/srep38489 · Cited by 43
Recent Advances in Aging and Immunosenescence: Mechanisms and Therapeutic Strategies
Wang, S., Huo, T., Lu, M., Zhao, Y., Zhang, J., He, W., & Chen, H. (2025) · Cells · doi:10.3390/cells14070499 · Cited by 47
“…p16Ink4a to design a novel transgenic mouse model, INK-ATTAC , that induces the elimination of p16Ink4a -positive SCs upon drug administration, and showed that using genetic methods to eliminate SCs can significantly delay the onset of age-related diseases and prolong healthy lifespan [15].”
Lorenzo, E. C., Torrance, B. L., Keilich, S. R., Al‐Naggar, I. M., Harrison, A. G., Xu, M., Bartley, J. M., & Haynes, L. (2021) · Aging Cell · doi:10.1111/acel.13525 · Cited by 47
Graf, M., Hartmann, N., Reichwald, K., & Englert, C. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.02.012 · Cited by 42
Targeting the phospholipase A2 receptor ameliorates premature aging phenotypes
Griveau, A., Wiel, C., Calvé, B. L., Ziegler, D. V., Djebali, S., Warnier, M., Martin, N., Marvel, J., Vindrieux, D., Bergö, M. O., et al. (2018) · Aging Cell · doi:10.1111/acel.12835 · Cited by 41
“Indeed, eliminating senescent cells in mice with a progeroid syndrome delays some age‐associated disorders, while in wild‐type mice it reduces aging‐related diseases and extends lifespan (Baker et al., 2016, 2011 ).”
BackgroundAdult Thymic Epithelium Contains Nonsenescent Label-Retaining Cells
Dumont-Lagacé, M., Brochu, S., St-Pierre, C., & Perreault, C. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302961 · Cited by 41
Systematic Review of Studies on Telomere Length in Patients with Multiple Sclerosis
Bühring, J., Hecker, M., Fitzner, B., & Zettl, U. K. (2021) · Aging and Disease · doi:10.14336/ad.2021.0106 · Cited by 39
“Studies with mice showed that removal of senescent cells can prevent or delay tissue dysfunction [80].”
BackgroundExtracellular Vesicles, Ageing, and Therapeutic Interventions
Panagiotou, N., Neytchev, O., Selman, C., & Shiels, P. G. (2018) · Cells · doi:10.3390/cells7080110 · Cited by 42
“Benefits from the clearance of senescent cells in a number of models have included protection from cancer, cardiovascular disease, and a lifespan increase of up to 30% [8,9,69,76].”
BackgroundIdentification of SYK inhibitor, R406 as a novel senolytic agent
Cho, H.-J., Yang, E. J., Park, J. T., Kim, J., Kim, E.-C., Jung, K., Park, S. C., & Lee, Y. (2020) · Aging · doi:10.18632/aging.103135 · Cited by 40
“In contrast, the clearance of p16-positive senescent cells extends lifespan in an aging-induced transgenic mouse model, INK-ATTAC mice [14], and a mouse model of a human progeroid syndrome, Ercc1-/ mice [15].”
BackgroundPlatelets in aging and cancer—“double-edged sword”
Faria, A. V. S., Andrade, S. S., Peppelenbosch, M. P., Ferreira-Halder, C. V., & Fuhler, G. M. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09926-2 · Cited by 38
Selvam, S. P., Roth, B. M., Nganga, R., Kim, J., Cooley, M. A., Helke, K. L., Smith, C. D., & Öğretmen, B. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003506 · Cited by 42
“Moreover, recent studies suggest that p16-expressing cells shorten a healthy life span (51) and that targeting p16 to clear senescent cells delays aging-related disorders detected in adipose tissue, skeletal muscle, and eye (52) or rejuvenates aged hematopoietic stem cells in mice (53).”
BackgroundFrailty and HIV: Moving from Characterization to Intervention
Erlandson, K. M., & Piggott, D. A. (2021) · Current HIV/AIDS Reports · doi:10.1007/s11904-021-00554-1 · Cited by 44
Chelvanambi, S., Gupta, S. K., Chen, X., Ellis, B. W., Maier, B. F., Colbert, T. M., Kuriakose, J., Zorlutuna, P., Jolicoeur, P., Obukhov, A. G., et al. (2019) · Circulation Research · doi:10.1161/circresaha.119.315082 · Cited by 39
Kim, Y. H., & Park, T. J. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.1.295 · Cited by 42
“For example, these cells have been observed not only in normal finger digit development, but also in examples of aging pathology, such as cataracts, osteoarthritis and atherosclerosis (9-13).”
BackgroundRegulation of senescence by microRNA biogenesis factors
Abdelmohsen, K., Srikantan, S., Kang, M. J., & Gorospe, M. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.01.003 · Cited by 39
Should we treat aging as a disease? The consequences and dangers of miscategorisation
Faragher, R. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00171 · Cited by 44
Focus on senescence: Clinical significance and practical applications
Boccardi, V., Orr, M. E., Polidori, M. C., Ruggiero, C., & Mecocci, P. (2024) · Journal of Internal Medicine · doi:10.1111/joim.13775 · Cited by 40
“I N K A T T A C [ 131 ] M i c r o g li a a n d a s t r o c y t es [ 131 ] C h e m o g e n e t i cs ( A P20187 ) [ 132 ] A B T263 ( N a v i t o c l a x ) [ 108 ] R e d u ce d t a u p a t h o l o gy , se n esce n ce , S A S P , i n fl a mm a t i o n , a n d c o g n i t i ve d ec li n e [ 131 ] P S 19…”
Cellular senescence causes ageing
Gil, J. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0128-0 · Cited by 39
The Aging Liver: Redox Biology and Liver Regeneration
Bellanti, F., & Vendemiale, G. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0048 · Cited by 40
“Budding uninhibited by benzimidazole-related 1 (BubR1) prevents chromosome unequal segregation during mitosis, and its decreased expression is associated with cell senescence (6–8).”
Age-Related Midbrain Inflammation and Senescence in Parkinson’s Disease
Russo, T., & Rießland, M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.917797 · Cited by 38
“Inflammation is a characteristic hallmark of many neurodegenerative disorders, including AD, ALS, multiple sclerosis (MS), and PD (Baker et al., 2011; Chitnis and Weiner, 2017; Trias et al., 2019) and there is evidence that the immune cells play an active role.”
BackgroundWang, P., Teng, S., Chengyu, Z., Cui, Z. G., Ma, C., Yu, Y., Lei, Z., Min, M., Zongyi, W., Yang, M., et al. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.05.017 · Cited by 42
Zhou, H., Khan, D., Hussain, S. M., Gerdes, N., Hagenbeck, C., Rana, M., Cornelius, J. F., & Muhammad, S. (2023) · Journal of Inflammation · doi:10.1186/s12950-023-00366-7 · Cited by 43
“This accumulation of senescent cells can negatively affect life span and promote age-related diseases, including cardiovascular diseases [1, 6, 7].”
BackgroundFranzin, R., Stasi, A., Ranieri, E., Netti, G. S., Cantaluppi, V., Gesualdo, L., Stallone, G., & Castellano, G. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.630419 · Cited by 41
Cellular senescence and the blood–brain barrier: Implications for aging and age-related diseases
Knopp, R. C., Erickson, M. A., Rhea, E. M., Reed, M. J., & Banks, W. A. (2023) · Experimental Biology and Medicine · doi:10.1177/15353702231157917 · Cited by 47
Long-term stimulation of angiotensin II induced endothelial senescence and dysfunction
Li, R., Mi, X., Yang, S., Yang, Y., Zhang, ., Hui, R., Chen, Y., & Zhang, W. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.02.012 · Cited by 39
“…endothelial cells with senescent features are present in the human atherosclerotic plaques (Minamino et al., 2002; Minamino and Komuro, 2007), and clearance of senescent cells can prevent the vessel dysfunction and extend health span in an accelerated-aging mouse model (Baker et al., 2011).”
BackgroundA guide to senolytic intervention in neurodegenerative disease
Lee, S., Wang, E. Y., Steinberg, A. B., Walton, C. C., Chinta, S. J., & Andersen, J. K. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111585 · Cited by 43
G Protein-Coupled Receptor Systems as Crucial Regulators of DNA Damage Response Processes
Leysen, H., van Gastel, J., Hendrickx, J. O., Santos‐Otte, P., Martin, B., & Maudsley, S. R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102919 · Cited by 37
“a functional ‘dead end’ of cell physiology, evidence gathered over recent years has demonstrated the importance of senescence-related signaling in processes such as embryonic development [131], wound healing/repair [132,133] and, most importantly, aging [134,135].”
BackgroundPathways from senescence to melanoma: focus on MITF sumoylation
Leclerc, J., Ballotti, R., & Bertolotto, C. (2017) · Oncogene · doi:10.1038/onc.2017.292 · Cited by 43
Senescent cells at the crossroads of aging, disease, and tissue homeostasis
Kuehnemann, C., & Wiley, C. D. (2023) · Aging Cell · doi:10.1111/acel.13988 · Cited by 44
“The models that selectively eliminate these cells have proven especially important, demonstrating that p16-and p21-positive cells limit both life span and health span (Baker et al., 2011; Wang et al., 2021).”
BackgroundThe functional impact of nuclear reorganization in cellular senescence
Rocha, A., Dalgarno, A., & Neretti, N. (2022) · Briefings in Functional Genomics · doi:10.1093/bfgp/elab012 · Cited by 38
“The causal link between senescent cell accumulation and tissue dysfunction has been demonstrated in rodents, as clearance of senescent cells led to a significant increase in both healthspan and lifespan [8].”
BackgroundLncRNAs regulating stemness in aging
Sousa‐Franco, A., Rebelo, K., da Rocha, S. T., & de Jesus, B. B. (2018) · Aging Cell · doi:10.1111/acel.12870 · Cited by 38
“…of the number of senescent cells impacts in the aging progression, demonstrating the feasibility of antisenescence thera- pies for age‐associated syndromes (Baker et al., 2011, 2016 ; Campisi & d'Adda di Fagagna, 2007; de Jesus & Blasco, 2012; Gil & Withers, 2016; Itahana, Campisi, & Dimri, 2007).”
BackgroundBcl-xL as a Modulator of Senescence and Aging
Mas‐Bargues, C., Borrás, C., & Viña, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041527 · Cited by 39
“Removal of senescent cells in these tissues reduces local inflammation and rescues some of the associated tissue impairments [76,89].”
BackgroundLevel of macroautophagy drives senescent keratinocytes into cell death or neoplastic evasion
Deruy, E., Nassour, J., Martin, N., Vercamer, C., Malaquin, N., Bertout, J., Chelli, F., Pourtier, A., Pluquet, O., & Abbadie, C. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.533 · Cited by 42
Pak2 kinase promotes cellular senescence and organismal aging
Lee, J.-S., Mo, Y., Gan, H., Burgess, R. J., Baker, D. J., van Deursen, J. M., & Zhang, Z. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903847116 · Cited by 39
Self-citationSenescence Inducer Shikonin ROS-Dependently Suppressed Lung Cancer Progression
Zheng, H., Huang, Q., Huang, S., Yang, X., Zhu, T., Wang, W., Wang, H., He, S., Ji, L., Wang, Y., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00519 · Cited by 39
“Meanwhile, previous study also revealed that apoptosis is the ultimate biological consequence for senescent cells in vivo (Baker et al., 2011).”
BackgroundTshilenge, K., Aguirre, C. G., Bons, J., Gerencser, A. A., Basisty, N., Song, S., Rose, J., Lopez‐Ramirez, A., Naphade, S. B., Loureiro, A., et al. (2023) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2023.100534 · Cited by 42
“Recent studies in mouse models of AD and PD suggest cellular senescence is important in disease progression and pathogenesis (10, 87-91).”
BackgroundLarsen, S. A., Kassem, M. S., & Rattan, S. I. S. (2012) · Chemistry Central Journal · doi:10.1186/1752-153x-6-18 · Cited by 38
“Additionally, p16 in particular may play a role in the initiation of the senescence programme [31,32].”
BackgroundInduction and transmission of oncogene-induced senescence
Rattanavirotkul, N., Kirschner, K., & Chandra, T. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03638-0 · Cited by 41
Cellular senescence as a therapeutic target to improve renal transplantation outcome
van Willigenburg, H., de Keizer, P. L. J., & de Bruin, R. W. F. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.02.015 · Cited by 38
Conte, T. C., Duran-Bishop, G., Orfi, Z., Mokhtari, I., Deprez, A., Côté, I., Molina, T., Taeyeon, K., Tellier, L., Roussel, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39663-3 · Cited by 39
“Pioneer studies showed thatgeneticremovalofsenescentcellsexpressingthecellcycleinhibitor p16 in aging mice enhances their lifespan 20,22 .”
Wu, J., Saovieng, S., Cheng, I.-S., Liu, T., Hong, S., Lin, C.-Y., Su, I.-C., Huang, C., & Kuo, C. (2018) · Journal of Ginseng Research · doi:10.1016/j.jgr.2018.06.002 · Cited by 40
“Accumulation of senescent cells in adult tissues implicates functional decay in adults [9].”
BackgroundSenotherapeutics and Their Molecular Mechanism for Improving Aging
Park, J., & Shin, D. W. (2022) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2022.114 · Cited by 45
“Baker et al. (2011) first revealed a direct relationship between cellular senescence and age-related symptoms.”
Sundar, I. K., Rashid, K., Gerloff, J., Rangel‐Moreno, J., Li, D., & Rahman, I. (2018) · The FASEB Journal · doi:10.1096/fj.201701518r · Cited by 37
“Our data on SASP mediators and cellular senescence biomarkers identified in lungs of CS-exposed mice are comparable with SASP factors and senescence genes measured in senescent cells or in ageassociated pathologies (39, 40).”
BackgroundEndothelial SIRT1 as a Target for the Prevention of Arterial Aging: Promises and Challenges
Begum, M. K., Konja, D., Singh, S., Chłopicki, S., & Wang, Y. (2021) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001154 · Cited by 40
Caloric restriction maintains stem cells through niche and regulates stem cell aging
Maharajan, N., Vijayakumar, K. A., Jang, C. H., & Cho, G. (2019) · Journal of Molecular Medicine · doi:10.1007/s00109-019-01846-1 · Cited by 38
“Use of a mouse model showed that the clearance of senescent cell positive marker p16 from the senescent cells delayed aging and agingrelated pathology, while late-life clearance may attenuate the aging-related pathologies [61].”
BackgroundMiller, K. N., Li, B., Pierce-Hoffman, H. R., Patel, S., Lei, X., Rajesh, A., Teneche, M. G., Havas, A. P., Gandhi, A., Macip, C. C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57229-3 · Cited by 47
Cellular senescence in ischemia/reperfusion injury
Chen, C., Zheng, M., Hou, H., Fang, S., Chen, L., Yang, J., Yao, W., Zhang, Q., & Hei, Z. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01205-z · Cited by 41
“Increasing pieces of evidence have shown that senolytics might be effective tools to eliminate senescent cells to treat age-related diseases and IR-induced cellular senescence [34].”
BackgroundMid-old cells are a potential target for anti-aging interventions in the elderly
Kim, Y. H., Lee, Y., Park, S. S., Park, S. H., Eom, S. Y., Lee, Y., Lee, W. J., Jang, J., Seo, D., Kang, H. Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43491-w · Cited by 44
“Moreover, senescent cells signi fi cantly affect the surrounding microenvironment by inducing sterile chronic in fl ammation through the secretion of senescence-associated secretory phenotypes (SASPs), which are known as “ in fl ammaging ” phenomena 6,7 .”
Yuan, Y., Hakimi, P., Kao, C., Kao, A. H., Liu, R., Janocha, A. J., Tressler, A. B., Hang, X., Alhoraibi, H., Slater, E., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.691766 · Cited by 39
“Another key component of aging at the cellular level is senescence (44).”
BackgroundAmelioration of age‐related brain function decline by Bruton's tyrosine kinase inhibition
Ekpenyong‐Akiba, A. E., Poblocka, M., Althubiti, M., Rada, M., Jurk, D., Germano, S., Kocsis‐Fodor, G., Shi, Y., Canales, J. J., & Macip, S. (2019) · Aging Cell · doi:10.1111/acel.13079 · Cited by 45
“According to recent reports (Baker et al., 2016, 2011), this could lead to an amelioration of age-related conditions and an increased lifespan.”
BackgroundResultSenescence in the aging process
Faragher, R., McArdle, A., Willows, A. O. D., & Ostler, E. L. (2017) · F1000Research · doi:10.12688/f1000research.10903.1 · Cited by 38
The mTORC1-autophagy pathway is a target for senescent cell elimination
Kucheryavenko, O., Nelson, G., von Zglinicki, T., Korolchuk, V. I., & Carroll, B. (2019) · Biogerontology · doi:10.1007/s10522-019-09802-9 · Cited by 39
Mazzucco, A. E., Smogorzewska, A., Kang, C., Luo, J., Schlabach, M. R., Xu, Q., Patel, R., & Elledge, S. J. (2017) · Genes & Development · doi:10.1101/gad.304857.117 · Cited by 35
Shakoor, A., Wang, B., Fan, L., Kong, L., Gao, W., Sun, J., Man, K., Li, G., & Sun, D. B. (2021) · Small · doi:10.1002/smll.202103086 · Cited by 37
Therapy-Induced Stromal Senescence Promoting Aggressiveness of Prostate and Ovarian Cancer
Pardella, E., Pranzini, E., Nesi, I., Parri, M., Spatafora, P., Torre, E., Muccilli, A., Castiglione, F., Fambrini, M., Sorbi, F., et al. (2022) · Cells · doi:10.3390/cells11244026 · Cited by 41
Aged cells in human skeletal muscle after resistance exercise
Yang, C., Jiao, Y., Wei, B., Yang, Z., Wu, J., Jensen, J., Jean, W., Huang, C., & Kuo, C. (2018) · Aging · doi:10.18632/aging.101472 · Cited by 37
“Selective elimination of senescence cells in skeletal muscle and other tissues has been shown to increase lifespan in mice [3], suggesting a promising approach for anti-aging intervention.”
BackgroundMazan-Mamczarz, K., Tsitsipatis, D., Childs, B. G., Carr, A. E., Dos Santos, C. R., Anerillas, C., Romero, B., Gregg, J. M., Henry-Smith, C., Okereke, A. N., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00889-z · Cited by 48
Self-citationAlveolar epithelial regeneration in the aging lung
Han, S., Budinger, G. R. S., & Gottardi, C. J. (2023) · Journal of Clinical Investigation · doi:10.1172/jci170504 · Cited by 40
“In these models, promoting apoptosis of p16-expressing cells resulted in improvements in age-related dysfunction (141, 143–146).”
Ni, J., Au, M. T., Kong, H., Wang, X., & Wen, C. (2021) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-021-03385-0 · Cited by 37
“Over the past decade, senescence has been linked with ageing and age-related pathologies [82, 83], including OA [12, 68].”
BackgroundSmall Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways
Al-Habib, M. A., Yu, Z., & Huang, G. T. ‐. (2013) · Stem Cells and Development · doi:10.1089/scd.2012.0426 · Cited by 37
“SC1 and rapamycin, more conspicuously than BIO, increased the levels of these pluripotent genes, while suppressing p16, which is a cyclin-dependent kinase inhibitor (CKI) that prevents cells from entering the cell cycle phases and is associated with cell senescence [36].”
Backgroundp53 and rapamycin are additive
Christy, B. A., Demaria, M., Campisi, J., Huang, J. L., Jones, D., Dodds, S. G., Williams, C. E., Hubbard, G. B., Livi, C. B., Gao, X., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4602 · Cited by 37
“A reduced SASP could also impact aging since the elimination of senescent cells ameliorated a variety of age-related pathologies in an early aging mouse model [63] and since eRapa ameliorated aging in wild type mice [4, 14-17].”
BackgroundMitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease
Hruby, A. J., & Higuchi‐Sanabria, R. (2025) · npj Aging · doi:10.1038/s41514-025-00291-4 · Cited by 52
Lewińska, A., Wróbel, K., Błoniarz, D., Adamczyk‐Grochala, J., Wołowiec, S., & Wnuk, M. (2022) · Biomaterials Advances · doi:10.1016/j.bioadv.2022.213047 · Cited by 38
Barnes, P. J. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_3 · Cited by 37
mTOR Inhibition Rejuvenates the Aging Gingival Fibroblasts through Alleviating Oxidative Stress
Xia, Y., Sun, M., Xie, Y., & Shu, R. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/6292630 · Cited by 39
“Senescent cells that accumulate during aging may have profound meanings at organism level, and the clearance of accumulated senescent cells may help to prevent tissue disorder and extend health span [24].”
BackgroundThe impact of ageing mechanisms on musculoskeletal system diseases in the elderly
Cai, Y., Han, Z., Cheng, H., Li, H., Wang, K., Chen, J., Liu, Z., Xie, Y., Lin, Y., Zhou, S., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1405621 · Cited by 51
“…a cell-permeable molecule used to dimerize the FK506-binding protein (FKBP) fusion protein, initiate biological signaling cascades and gene expression or disrupt protein-protein interactions, and treatment with AP20187 can reduce the expression of p16Ink4a, thereby improving bone loss (204, 205).”
BackgroundSolovyeva, E. M., Ibebunjo, C., Utzinger, S., Eash, J. K., Dunbar, A., Naumann, U., Zhang, Y., Serluca, F. C., Demirci, S., Oberhauser, B., et al. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111510 · Cited by 35
“Tmem158 complemented the known senescence markers Cdkn2a (p16ink4) with a role in skeletal muscle (Baker et al., 2011; Sousa-Victor et al., 2014) as well as Cdkn1a (p21) as a marker for post-mitotic senescence (Jurk et al.”
Madani, A. Y., Majeed, Y., Abdesselem, H., Agha, M. V., Vakayil, M., Sukhun, N. K. A., Halabi, N. M., Kumar, P., Hayat, S., Elrayess, M. A., et al. (2021) · Antioxidants · doi:10.3390/antiox10020334 · Cited by 37
“It occurs as a result of various cellular stress responses and has been proposed to drive aging-related degenerative disorders [8] and tumor progression [9].”
BackgroundLee, J.-S., & Zhang, Z. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600509113 · Cited by 38
Adult Cardiac Stem Cell Aging: A Reversible Stochastic Phenomenon?
Cianflone, E., Torella, M., Chimenti, C., Angelis, A. D., Beltrami, A. P., Urbanek, K., Rota, M., & Torella, D. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/5813147 · Cited by 40
Identification of gingerenone A as a novel senolytic compound
Moaddel, R., Rossi, M. S., Rodriguez, S., Munk, R. B., Khadeer, M., Abdelmohsen, K., Gorospe, M., & Ferrucci, L. (2022) · PLoS ONE · doi:10.1371/journal.pone.0266135 · Cited by 46
Central role for cholangiocyte pathobiology in cholestatic liver diseases
Jalan-Sakrikar, N., Guicciardi, M. E., O’Hara, S. P., Azad, A., LaRusso, N. F., Gores, G. J., & Huebert, R. C. (2025) · Hepatology · doi:10.1097/hep.0000000000001093 · Cited by 38
Alsuraih, M., O’Hara, S. P., Woodrum, J. E., Pirius, N., & LaRusso, N. F. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100250 · Cited by 38
“Upon administration of AP20187, a synthetic drug that induces membrane-bound FKBP-Casp8 dimerization, apoptosis is induced in cells expressing p16.(26) A double-homozygous INK-ATTACxMdr2 mouse (hereafter ATTACxMdr2) was successfully bred.”
BackgroundMethodInfluentialTelomeres as hotspots for innate immunity and inflammation
Nassour, J., Przetocka, S., & Karlseder, J. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103591 · Cited by 40
Vascular Dementia: From Pathophysiology to Therapeutic Frontiers
Yang, H. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14186611 · Cited by 48
Hastings, W. J., Shalev, I., & Belsky, D. W. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00164 · Cited by 36
“Accumulation of senescent cells is thought to be a core driver of aging-related decline in system integrity (Baker et al., 2011; Lopez-Otin et al., 2013; Akbar et al., 2016).”
BackgroundLiu, X., DILXAT, T., Shi, Q., Qiu, T., & Lin, J. (2022) · Gene · doi:10.1016/j.gene.2022.146348 · Cited by 34
Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence
Carapeto, P., Iwasaki, K., Hela, F., Kahng, J., Alves-Wagner, A. B., Middelbeek, R. J. W., Hirshman, M. F., Rutter, G. A., Goodyear, L. J., & Aguayo-Mazzucato, C. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01130-8 · Cited by 35
Senopathies-Diseases Associated with Cellular Senescence
Lushchak, O., Schosserer, M., & Grillari, J. (2023) · Biomolecules · doi:10.3390/biom13060966 · Cited by 35
“Ultimately, elegant experiments in mice showed that the accumulation of SCs during aging limits the healthy murine lifespan [14,15].”
BackgroundInfluentialInhibitory effects of juglanin on cellular senescence in human dermal fibroblasts
Yang, H. H., Hwangbo, K., Zheng, M. S., Son, J., Kim, H. Y., Baek, S. H., Choi, H. C., Park, S., & Kim, J. (2014) · Journal of Natural Medicines · doi:10.1007/s11418-014-0817-0 · Cited by 36
mTOR as a senescence manipulation target: A forked road
Saoudaoui, S., Bernard, M., Cardin, G. B., Malaquin, N., Christopoulos, A., & Rodier, F. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.02.002 · Cited by 36
Aging and the Biological Response to Liver Injury
Marzioni, M., Pinto, C., Ninfole, E., Gaggiano, L., Benedetti, A., & Maroni, L. (2020) · Seminars in Liver Disease · doi:10.1055/s-0039-3402033 · Cited by 36
Metabolic remodeling in cancer and senescence and its therapeutic implications
Kim, Y., Jang, Y., Kim, M.-S., & Kang, C. (2024) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2024.02.008 · Cited by 36
Wang, Y., Wang, Y., Yang, M., & Ma, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111191 · Cited by 34
p53 regulated senescence mechanism and role of its modulators in age-related disorders
Pawge, G., & Khatik, G. L. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114651 · Cited by 38
Immune and inflammatory responses to DNA damage in cancer and aging
Soria‐Valles, C., López‐Soto, A., Osorio, F. G., & López-Otín, C. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.10.004 · Cited by 36
Lucke-Wold, B. P., Turner, R. C., Lucke-Wold, N., Rosen, C. L., & Huber, J. D. (2012) · Europe PMC (PubMed Central) · Cited by 36
Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss
Chacón, L. D. M. R., Martínez-Rodríguez, S., Madrid, R., Yanes‐Diaz, J., Riestra‐Ayora, J., Fernández, R. S., & Sánchez‐Rodríguez, C. (2021) · Antioxidants · doi:10.3390/antiox10091497 · Cited by 37
“Numerous aging pathologies associated with senescence have been studied, as in glaucoma [11], cataracts [12], the diabetic pancreas [13], osteoarthritis [14], and cancer [15].”
BackgroundSenescence induction universally activates transposable element expression
Colombo, A., Elias, H. K., & Ramsingh, G. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1502576 · Cited by 37
Yang, H. H., Hwangbo, K., Zheng, M. S., Cho, J. H., Son, J., Kim, H. Y., Baek, S. H., Choi, H. C., Park, S., & Kim, J. (2014) · Archives of Pharmacal Research · doi:10.1007/s12272-014-0344-2 · Cited by 38
Molecular Mechanisms of Cellular Senescence in Neurodegenerative Diseases
Lee, H.-J., Yoon, Y.-S., & Lee, S.-J. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168114 · Cited by 36
Metadata
- Authors
- Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Venue
- Nature
- Published
- 2011-11
- Volume
- 479
- Issue
- 7372
- Pages
- 232-236
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3468323
- OpenAlex
- W2069519394
- Cited by
- 3,670
- References
- 32
- Citations by year
- 2026: 221 · 2025: 284 · 2024: 347 · 2023: 316 · 2022: 333 · 2021: 333 · 2020: 324 · 2019: 299 · 2018: 250 · 2017: 190 · 2016: 203 · 2015: 157 · 2014: 159 · 2013: 127 · 2012: 119
- FWCI
- 89.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Institute on Aging (P01AG041122, AG 13925, R01AG013925, R37AG013925)
- National Cancer Institute (CA-96985, R01CA096985)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK050456)
- 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
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, senolytics, senolytic therapy, p16INK4a, senescent cell clearance, aging, age-related diseases, healthspan extension, adipose tissue, skeletal muscle, eye, tissue dysfunction
- MeSH terms
- Adipose Tissue, Aging, Animals, Bone Marrow Cells, Cell Count, Cells, Cultured, Eye, Female, Genotype, Longevity, Male, Mice, Transgenic, Phenotype, Progeria, Time Factors, Weaning, Gene Expression, Tacrolimus, Cellular Senescence, Protein Serine-Threonine Kinases, Muscle, Skeletal, Cell Cycle Proteins, Cyclin-Dependent Kinase Inhibitor p16, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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