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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Written from the paper’s full text.
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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- Based: passes — The paper gives a reason why it holds.
- 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.
- 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.
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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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 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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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.
- Checkable: passes — It can be checked against evidence.
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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
“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
“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
“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
“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
“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]
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
“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]
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
“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]
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
“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]
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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“11,12 However, attempts to translate these results into humans are hindered by the difficulty of targeting wild-type senescent cells in vivo with sufficient specificity.”
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“…including atherosclerosis, diabetes, idiopathic pulmonary fibrosis, osteoarthritis, and neurodegenerative diseases ( Baker et al., 2016 ; Baker et al., 2011 ; Childs et al., 2015 ; Zhu et al., 2015 ; Chang et al., 2016 ; Kim and Kim, 2019 ; Kirkland et al., 2017 ; van Deursen, 2019 ;…”
BackgroundImmunosenescence of brain accelerates Alzheimer’s disease progression
Chen, H.-Y., Zhao, Y. G., & Xie, Y. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2022-0021 · Cited by 12
Chen, Y., Jiang, F., Kong, G., Yuan, S., Cao, Y., Zhang, Q., Wang, Q., & Liu, L. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9926284 · Cited by 12
Concise Review: Challenges in Regenerating the Diabetic Heart: A Comprehensive Review
Satthenapalli, V. R., Lamberts, R. R., & Katare, R. (2017) · Stem Cells · doi:10.1002/stem.2661 · Cited by 13
Cellular senescence and tumor promotion: Role of the Unfolded Protein Response
Pluquet, O., & Abbadie, C. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.01.001 · Cited by 12
Laget, J., Hobson, S., Muyor, K., Duranton, F., Cortijo, I., Bartochowski, P., Jover, B. F., Lajoix, A., Söderberg, M. P., Ebert, T., et al. (2023) · Cells · doi:10.3390/cells12040643 · Cited by 12
“Senolytics, compounds that specifically target senescent cells, can ameliorate diseasespecific dysfunctions [18].”
BackgroundHunday, G., Sivanandam, M., & Kumaradhas, P. (2019) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2019.1699446 · Cited by 12
Translation of Cellular Senescence to Novel Therapeutics: Insights From Alternative Tools and Models
Inci, N., Kamali, D., Akyildiz, E. O., Tahir Turanli, E., & Bozaykut, P. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.828058 · Cited by 13
Loss of DNA polymerase β induces cellular senescence
Ahmed, A. A., Smoczer, C., Pace, B. R., Patterson, D. W., & Cabelof, D. C. (2018) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22206 · Cited by 12
“The increase in p16 in both model systems may be therapeutically interesting, as elimination of p16 expressing cells can reverse some age associated phenotypes [Baker et al., 2011].”
BackgroundDu, H., Wang, Y., Liu, X., Wang, S., Wu, S., Yuan, Z., & Zhu, X. (2020) · Cytokine · doi:10.1016/j.cyto.2020.155314 · Cited by 12
Senescence marker p16INK4a expression in patients with multiple sclerosis
Yang, J. H., Miner, A. E., Fair, A. E., Kinkel, R. P., & Graves, J. S. (2024) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2024.105498 · Cited by 13
Systematic Review of the Use of Phytochemicals for Management of Pain in Cancer Therapy
Harrison, A. M., Heritier, F., Childs, B. G., Bostwick, J. M., & Dziadzko, M. A. (2015) · BioMed Research International · doi:10.1155/2015/506327 · Cited by 12
“For example, the molecular signaling pathways and other mechanisms regulating the natural aging process, as well as chronic illnesses of aging, have been partially elucidated through an understanding of cellular senescence [41].”
BackgroundSelf-citationImmune senescence: A key player in cancer biology
Yang, Y., Fan, L., Li, M., & Wang, Z. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.12.001 · Cited by 15
Cellular senescence in metastatic prostate cancer: A therapeutic opportunity or challenge (Review)
Jin, C., Liao, S., Lu, G., Geng, B. D., Ye, Z., Xu, J., Ge, G., & Yang, D. (2024) · Molecular Medicine Reports · doi:10.3892/mmr.2024.13286 · Cited by 12
Okamoto, M., Nakashima, H., Sakai, K., Takegami, Y., Osawa, Y., Watanabe, J., Ito, S., Hibi, H., & Imagama, S. (2024) · Scientific Reports · doi:10.1038/s41598-024-53400-w · Cited by 13
“An alternative to senolytics, is the senomorphic approach, which involves the alleviation of cellular senescence-related phenotypes without eliminating senescent cells 26,31 .”
BackgroundDevrukhkar, P. R., Watson, M. A., Soygur, B., Wu, F., Bons, J., Anvari, H., Atazhanova, T., Martin, N., Tran, T., Schneider, K., et al. (2025) · Aging Cell · doi:10.1111/acel.70111 · Cited by 17
“Thus, while cell culture is a simpler system to study cellular senescence, removing cells from their complex 3D-native state in tissue and studying them in a 2D controlled microenvironment greatly diminishes their translational value (Baker et al. 2011; Folgueras et al. 2018).”
Senescent and disease-associated microglia are modifiable features of aged brain white matterPreprint
Schafer, M. J., Carver, C., Gomez, P., Rodriguez, S., Kachergus, J. M., Liu, Y., Shi, J., Tran, T., Wang, L., Melov, S., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3467812/v1 · Cited by 12
Theory and associated phenomenology for intrinsic mortality arising from natural selection
Werfel, J., Ingber, D. E., & Bar-Yam, Y. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173677 · Cited by 12
“…of inevitable breakdowns or genetic tradeoffs, then effective health and life extensions through dietary, pharmacological, or genetic interventions [50, 51, 104–111] are likely to be possible, with potential for significant impact (e.g., altering two genes extends nematode lifespan fivefold [10]).”
A single short reprogramming early in life improves fitness and increases lifespan in old age
(2021) · doi:10.1101/2021.05.13.443979 · Cited by 12
“It has been demonstrated on progeric and non-progeric mice in seminal works on a genetically modified model triggering apoptosis in p16 expressing cells (55, 56).”
BackgroundRole of DNA damage in the pathogenesis of atherosclerosis
Ishida, M., Sakai, C., & Ishida, T. (2022) · Journal of Cardiology · doi:10.1016/j.jjcc.2022.08.010 · Cited by 12
Nadeau, S., Cheng, A., Colmegna, I., & Rodier, F. (2019) · Methods in molecular biology · doi:10.1007/7651_2019_217 · Cited by 13
Stromal senescence contributes to age-related increases in cancer
Ye, J., Melam, A., & Stewart, S. A. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00840-9 · Cited by 16
“…senescence was originally observed in tissue culture, the development of innovative mouse models that allow senescent cells to be specifically killed or tracked with lineage tracers (Table 1) has demonstrated that cellular senescence is a contributor to age-related diseases, including cancer 8 .”
Gao, Y., Xu, L., Li, Y., Qi, D., Wang, C., Luan, C., Zheng, S., Du, Q., Liu, W., Lu, G., et al. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.111902 · Cited by 12
Current aspects of targeting cellular senescence for the therapy of neurodegenerative diseases
Jaganathan, R., Iyaswamy, A., Krishnamoorthi, S., Thakur, A., Durairajan, S. S. K., Yang, C., & Wankhar, D. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1627921 · Cited by 12
“With aging, there is a buildup of senescent cells that release pro-inflammatory and toxic substances, potentially leading to impaired neuronal function and the promotion of neuroinflammation (Baker et al., 2011; Freund et al., 2010; Regen et al., 2017).”
InfluentialCellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma
Salam, R., Saliou, A., Bielle, F., Bertrand, M., Antoniewski, C., Carpentier, C., Alentorn, A., Capelle, L., Sanson, M., Huillard, E., et al. (2022) · doi:10.1101/2022.05.18.492465 · Cited by 132
Identification of a Proteomic Signature of Senescence in Primary Human Mammary Epithelial Cells
Delfarah, A., Hartel, N. G., Zheng, D., Yang, J., & Graham, N. A. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00659 · Cited by 8
Exploring replication stress and cellular senescence as key targets in novel cancer therapies
Ray, S. K., & Mukherjee, S. (2025) · Cancer Genetics · doi:10.1016/j.cancergen.2025.09.002 · Cited by 14
To senesce or not to senesce: how primary human fibroblasts decide their cell fate after DNA damage
Kollárovič, G., Studencka‐Turski, M., Ivanova, L., Lauenstein, C., Heinze, K., Lapytsko, A., Talemi, S. R., Figueiredo, A. S., & Schaber, J. (2016) · Aging · doi:10.18632/aging.100883 · Cited by 11
“However, as senescent cells accumulate in tissue with age adverse effects become increasingly relevant and are believed to contribute to organismal aging [1, 55, 56].”
BackgroundCheng, H., Gao, X., Huard, M., Lu, A., Ruzbarsky, J. J., Amra, S., Wang, B., & Huard, J. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-03047-z · Cited by 12
“P16 was found to increase with age, accumulate, and modulate specific age-associated stem cell functions [43], and as such increased expression of P16 is a hallmark of aging and cells senescence [44].”
BackgroundZhou, L., DeMarco, K. D., Murphy, K. C., Wu, Z., Li, J., Johnson, C., Liu, B., Giwa, H. K., Ma, B., Bhalerao, N., et al. (2025) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-1212 · Cited by 18
Okudaira, N., Akimoto, M., Susa, T., Akimoto, M., Hisaki, H., Iizuka, M., Okinaga, H., Almunia, J. A., Ogiso, N., Okazaki, T., et al. (2024) · Aging Cell · doi:10.1111/acel.14206 · Cited by 11
“To determine the role of senescence in aging-related diseases, the INK-ATTAC mouse model was established in which p16-expressing senescent cells could be eliminated (Baker et al., 2011).”
Cellular senescence and developmental defects
Klein, A., Rhinn, M., & Keyes, W. M. (2023) · FEBS Journal · doi:10.1111/febs.16731 · Cited by 14
Sugiyama, Y., Harada, T., Kamei, Y., Yasuda, T., Mashimo, T., Nishikimi, A., & Maruyama, M. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112130 · Cited by 12
Park, S. S., Lee, Y., Kim, Y. H., Park, S. H., Kang, H. Y., Kim, J. C., Kim, D. J., Lim, S. B., Yoon, G., Kim, J., et al. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01354-4 · Cited by 15
“Previous studies applying senolytics 12 or selective cytotoxicity in p16 INK4A -overexpressed cells in aged mice 6 have been supported the notion that removal of senescent cells can be alleviate not all but many aging-related phenotypes and lead to the prolongation of life span.”
Skeletal Senescence with Aging and Type 2 Diabetes
Farr, J. N. (2023) · Endocrinology and Metabolism · doi:10.3803/enm.2023.1727 · Cited by 13
“, apoptosis through targeted activation of caspase 8), which harbors a “suicide” transgene driven by the p16 promoter [26].”
BackgroundPark, J.-J., Oh, K., Lee, G.-W., Bang, G., Park, J., Kim, H.-B., Kim, J. Y., Shin, E., & Kim, E. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-00966-6 · Cited by 15
“Senescence, a hallmark of aging, is a factor in aging and age-related diseases (ARDs) 3,4 , particularly lung diseases, including chronic obstructive pulmonary disease (COPD), whose major types are emphysema and chronic bronchitis 5,6 .”
Fan, Z., Li, L., Li, X., Zhang, M., Dou, M., Zhao, J., Cao, J., Deng, X., Zhang, M., Li, H., et al. (2019) · Aging · doi:10.18632/aging.101761 · Cited by 11
“com 583 AGING SA-β-gal assay has been viewed as the gold standard for identification of senescent cells [44–46] and has been the most extensively utilized biomarker for senescent cells in vitro and in vivo [47, 48].”
MethodThe role of RNA helicases in aging and lifespan regulation
Park, S., Park, H. H., Son, H. G., & Lee, S. (2017) · Translational Medicine of Aging · doi:10.1016/j.tma.2017.08.001 · Cited by 12
Imai, R., Asai, K., Hanai, J., & Takenaka, M. (2015) · Aging · doi:10.18632/aging.100779 · Cited by 11
“Chronic diseases, including cardiovascular disease, diabetes and cancer, account for a high rate of mortality [1], and aging is a notable risk factor for the progression of chronic diseases [2, 3].”
BackgroundLigustilide, A Novel Senolytic Compound Isolated from the Roots of Angelica Acutiloba
Takaya, K., & Kishi, K. (2024) · Advanced Biology · doi:10.1002/adbi.202300434 · Cited by 11
Mao, X., Li, L., Lee, G., Agborbesong, E., Zhou, J. X., Calvet, J. P., & Li, X. (2025) · Kidney International · doi:10.1016/j.kint.2025.05.027 · Cited by 12
Gromadzka, G., Tarnacka, B., & Cieślik, M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27010522 · Cited by 19
Restoring resident tissue macrophages to combat aging and cancer
Park, M. D., Yatim, N., Zhang, J., Cho, B. A., Yoo, S., Schaefer, M. M., Chowell, D., Puleston, D. J., & Mérad, M. (2025) · Nature Aging · doi:10.1038/s43587-025-00898-y · Cited by 14
“…(1) both immune and nonimmune cells become dysfunctional with age, converging on the state of ‘senescence’ that drives aging-related diseases 6–9 ; (2) heightened inflammation, partly fueled by cytokines secreted by senescent cells 10 , may contribute to the dysfunction of immune and…”
Rao, C. V., Sanghera, S., Zhang, Y., Biddick, L., Reddy, A., Lightfoot, S. A., Dai, W. H., & Yamada, H. Y. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22306 · Cited by 11
“Consistent with the idea that CIN induces senescence, mice with a hypomorphic allele of BubR1, a spindle checkpoint component defect which also leads to CIN, show premature aging that is at least partly dependent on p16 [48,49].”
BackgroundBMAL1 modulates senescence programming via AP-1
Jachim, S. K., Zhong, J., Ördög, T., Lee, J., Bhagwate, A. V., Nagaraj, N. K., Westendorf, J. J., Passos, J. F., Matveyenko, A. V., & LeBrasseur, N. K. (2023) · Aging · doi:10.18632/aging.205112 · Cited by 11
Self-citationThe caspase-activated DNase promotes cellular senescence
Haimovici, A., Rupp, V., Amer, T., Moeed, A., Weber, A., & Häcker, G. A. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00163-9 · Cited by 11
“Whole mount staining on white adipose tissue was performed as described (Baker et al, 2011) with the modi fi cation of an 8 h incubation time.”
Sharma, R., Kumar, R., Sharma, A., Goel, A., & Padwad, Y. S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.01.425058 · Cited by 11
“…suggest that selective ablation of senescent cells through senolytics and/or suppressing the development of cellular senescence/SASP can have strong implications in promoting longevity and attenuating the susceptibility to age-related disorders (Baker et al., 2011,2016; Palmer et al., 2019).”
BackgroundThe ING1a model of rapid cell senescence
Bertschmann, J., Thalappilly, S., & Riabowol, K. T. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.06.004 · Cited by 14
Waaijer, M. E. C., Wieser, M., Grillari‐Voglauer, R., et al. (2014) · Biogerontology · doi:10.1007/s10522-014-9496-1 · Cited by 11
“The importance of senescence in the aging process was previously observed in vivo as well, as clearance of p16INK4a positive cells was shown to delay agerelated pathologies in mice (Baker et al. 2011).”
BackgroundMassemin, A., Goehrig, D., Flaman, J., Jaber, S., Griveau, A., Djebali, S., Marcos, É., Payen, L. F., Marvel, J., Parent, R., et al. (2023) · Aging Cell · doi:10.1111/acel.13971 · Cited by 10
“Aging and a poor lifestyle (cigarette smoke, obesity, etc.) are known to promote cell entry into senescence and senescent cell accumulation and to decrease senescent cell elimination (Baker et al., 2011; Campisi, 2012; Di Micco et al., 2021; Kowald et al., 2020).”
BackgroundBiomarkers, interventions and healthy ageing
Kenessary, A., Zhumadilov, Z. S., Nurgozhin, T. S., Kipling, D., Yeoman, M. S., Cox, L. S., Ostler, E. L., & Faragher, R. (2012) · New Biotechnology · doi:10.1016/j.nbt.2012.11.018 · Cited by 11
En, A., Watanabe, K., Ayusawa, D., & Fujii, M. (2022) · FEBS Journal · doi:10.1111/febs.16584 · Cited by 11
Senescence in cancer: Hallmarks, paradoxes, and therapeutic promise
Hinterleitner, C., Goldberg, H. V., McHugh, D., Barthet, V. J. A., Filliol, A. A., & Lowe, S. W. (2026) · Cell · doi:10.1016/j.cell.2026.03.005 · Cited by 20
“The INK-ATTAC mouse 220 expresses a drug-inducible FKBP-caspase-8 fusion protein under the control of the p16 INK4a promoter, allowing for selective ablation of p16-expressing cells upon treatment with the dimerizing agent AP20187.”
Tumor-Associated Senescent Macrophages, Their Markers, and Their Role in Tumor Microenvironment
Pukhalskaia, T. V., Yurakova, T. R., Bogdanova, D. A., & Demidov, O. N. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924050055 · Cited by 12
Drug mechanism enrichment analysis improves prioritization of therapeutics for repurposing
Garana, B. B., Joly, J. H., Delfarah, A., Hong, H., & Graham, N. A. (2023) · BMC Bioinformatics · doi:10.1186/s12859-023-05343-8 · Cited by 12
Id1 expression in kidney endothelial cells protects against diabetes‐induced microvascular injury
Sharma, S. G., & Plotkin, M. D. (2020) · FEBS Open Bio · doi:10.1002/2211-5463.12793 · Cited by 11
Genetic and Epigenetic Inheritance at Telomeres
Lister‐Shimauchi, E. H., McCarthy, B., Lippincott, M. J., & Ahmed, S. C. (2022) · Epigenomes · doi:10.3390/epigenomes6010009 · Cited by 13
“Alternatively, even though senescent cells promote aging in mice [90], accumulation of senescent cells in aging humans may result in a cell-nonautonomous activity that suppresses tumor development [29].”
BackgroundRao, C. V., Farooqui, M., Asch, A. S., & Yamada, H. Y. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1515554 · Cited by 11
New Insights into Chronological Mobility of Retrotransposons In Vivo
Ghanam, A. R., Cao, J., Ouyang, X., & Song, X. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2818415 · Cited by 9
Rothmiller, S., Jäger, N., Meier, N., Meyer, T., Neu, A., Steinritz, D., Thiermann, H., Scherer, M. A., Rummel, C., Mangerich, A., et al. (2021) · Archives of Toxicology · doi:10.1007/s00204-020-02946-5 · Cited by 10
“2016), age-related diseases (Baker et al. 2011), tissue remodeling (Krizhanovsky et al.”
BackgroundGrowth hormone in adipose dysfunction and senescence
Stout, M. B., Tchkonia, T., & Kirkland, J. L. (2015) · Oncotarget · doi:10.18632/oncotarget.3997 · Cited by 11
Self-citationAlive and well? Exploring disease by studying lifespan
Brett, J. O., & Rando, T. A. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.05.004 · Cited by 12
Tyrosine Kinase Inhibition: a New Perspective in the Fight against HIV
Rodríguez-Mora, S., Spivak, A. M., Szaniawski, M. A., López‐Huertas, M. R., Alcamı́, J., Planelles, V., & Coiras, M. (2019) · Current HIV/AIDS Reports · doi:10.1007/s11904-019-00462-5 · Cited by 11
A new chronological survival assay in mammalian cell culture
Kaeberlein, M. R., & Kennedy, B. K. (2012) · Cell Cycle · doi:10.4161/cc.11.2.18959 · Cited by 10
Yeh, C. (2016) · Oral Diseases · doi:10.1111/odi.12483 · Cited by 11
“The ATTAC/BubR1 mice treated with lifelong AP showed delayed pathology in adipose, skeletal muscle, and eye tissues (Baker et al, 2011).”
BackgroundInfluentialWang, Y., Tseng, Y., Chen, K., Wang, X., Mao, Z., & Li, X. (2022) · Journal of Functional Biomaterials · doi:10.3390/jfb14010006 · Cited by 11
“reported that a transgenically induced reduction in the number of senescent cells can reduce the cataract rate in aging mice [11], which is consistent with our results.”
BackgroundResultWang, S., Zhai, J., Heng, K., Sha, L., Song, X., Zhai, H., Dai, C., Li, J., Teng, F., Huang, J., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-82262-5 · Cited by 13
“Genetic tactics, such as the removal of p16 Ink4a , have been shown to benefically impact longevity and age-related osteoporotic changes 22,48 .”
Okamura, K., Suzuki, T., & Nohara, K. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.115259 · Cited by 11
Gremlin 2 suppresses differentiation of stem/progenitor cells in the human skin
Kawagishi‐Hotta, M., Hasegawa, S., Inoue, Y., Hasebe, Y., Arima, M., Iwata, Y., Sugiura, K., & Akamatsu, H. (2021) · Regenerative Therapy · doi:10.1016/j.reth.2021.06.007 · Cited by 11
“In the mouse skin, removal of senescent cells restored the thickness of subcutaneous adipose tissue [58] or fur density [59].”
BackgroundConcise Review: The Epigenetic Contribution to Stem Cell Ageing: Can We Rejuvenate Our Older Cells?
Armstrong, L., Al-Aama, J. Y., Stojković, M., & Lako, M. (2014) · Stem Cells · doi:10.1002/stem.1720 · Cited by 11
Das, D. M., & Kale, V. P. (2021) · Cell Biology International · doi:10.1002/cbin.11691 · Cited by 11
Commentary on Some Recent Theses Relevant to Combating Aging: February 2017
Zealley, B., & de Grey, A. D. N. J. (2017) · Rejuvenation Research · doi:10.1089/rej.2017.1925 · Cited by 11
“…these cells (and more urgently, their toxic effects) by inhibiting Bcl-2 and its relatives have demonstrated remarkable system-wide rejuvenating effects in various models, 19 leading to the development of the new class of senolytic drugs—the first of which will soon enter human clinical trials.”
Lack of a p16/ARF locus in fish genome may underlie senescence resistance in the fish cell line, EPC
Futami, K., Sato, S., Maita, M., & Katagiri, T. (2022) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2022.104420 · Cited by 11
Progress in antisenescence biomaterials for improved osteoarthritis therapy
Ge, Y.-S., Ding, J.-Y., Shen, J., Meng, T.-T., Huang, C.-M., Li, W.-Y., Zhao, M.-J., Yin, J.-L., Zhai, Y.-Q., Wang, X., et al. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.08.044 · Cited by 13
Purinergic signaling promotes premature senescence
Volonté, D., Benson, C. J., Daugherty, S. L., Beckel, J. M., Trebak, M., & Galbiati, F. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107145 · Cited by 15
Ma, R., Wang, X., Ren, K., Ma, Y., Min, T., Yang, Y., Xie, X., Li, K., Zhu, K., Yuan, D., et al. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116214 · Cited by 11
New insight into vascular homeostasis and injury-reconstruction
Zhang, Y., & Dong, E. (2014) · Science China Life Sciences · doi:10.1007/s11427-014-4719-x · Cited by 11
Lemaı̂tre, J.-M. (2024) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.19820 · Cited by 13
“To address the question of whether senescent cells are the causative factor of age-related dysfunction and whether clearing them from tissues has a positive effect, Baker et al. 30 constructed an inducible transgene, INK-ATTAC , to selectively clear senescent cells expressing the p16 senescence biomarker upon administ…”
BackgroundFrailty as a Clinically Relevant Measure of Human Aging
Jung, H. (2021) · Annals of Geriatric Medicine and Research · doi:10.4235/agmr.21.0106 · Cited by 11
Ardestani, S. K., Jamali, T., Taravati, A., Behboudi, H., Mahdavi, M. R. V., Faghihzadeh, E., & Ghazanfari, T. (2022) · Drug and Chemical Toxicology · doi:10.1080/01480545.2022.2150205 · Cited by 11
Senescent cells in tissue engineering
Chin, A. F., & Elisseeff, J. H. (2022) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2022.102737 · Cited by 11
Voic, H., Li, X., Jang, J.-H., Zou, C., Sundd, P., Alder, J. K., Rojas, M. M., Chandra, D., Randell, S. H., Mallampalli, R. K., et al. (2019) · BMC Genomics · doi:10.1186/s12864-018-5409-z · Cited by 12
“Increase in the number of senescent cells, which are metabolically active but unable to divide, may play a causative role in the development of tissue and organ dysfunction and age-associated diseases through several mechanisms, including an altered secretory phenotype and lack of cell proliferation [5, 6].”
BackgroundPathological Role of Adipose Tissue Dysfunction in Cardio-Metabolic Disorders
Shimizu, I., Yoshida, Y., & Minamino, T. (2015) · International Heart Journal · doi:10.1536/ihj.14-401 · Cited by 11
Detecting Markers of Therapy-Induced Senescence in Cancer Cells
Fan, D. N.-Y., & Schmitt, C. A. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6670-7_4 · Cited by 14
“cells and is applicable to fresh or cryopreserved, unfixed material only (14) – established so far (5, 11, 31).”
BackgroundSkwarska, A., Ramachandran, S., Dobrynin, G., Leszczyńska, K. B., & Hammond, E. M. (2017) · Oncotarget · doi:10.18632/oncotarget.16102 · Cited by 12
“Whereas apoptotic or necrotic cell death results in the clearance of cancer cells, cells which cease to proliferate and enter a senescent state remain viable and retain their metabolic potential [11].”
BackgroundSlusher, A. L., Zúñiga, T. M., & Acevedo, E. O. (2019) · Mediators of Inflammation · doi:10.1155/2019/2324193 · Cited by 11
Cellular senescence in adult pulmonary hypertension: current state and future challenges
Lemay, S.-E. S., Kuwabara, Y., Bonnet, S., Potus, F., Provencher, S., Adnot, S., & Boucherat, O. (2025) · European Respiratory Review · doi:10.1183/16000617.0030-2025 · Cited by 15
“…senescent cells in the BubR1 progeroid mouse background has been shown to delay the onset of age-related pathologies in several tissues [141] and pre-term birth along with lung disease in infancy are associated with shorter telomere length and reduced lung function at 10 years of age…”
Giacconi, R., Malavolta, M., Costarelli, L., & Provinciali, M. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.09.015 · Cited by 10
“The finding regarding the clearance of p16Ink4a-positive senescent cells which delay aging-associated disorders in genetically engineered mice (Baker et al., 2011) opens interesting future perspectives regarding therapeutic approaches aimedat the removal of senescent cells to prevent or delay tissue dysfunction and ex…”
BackgroundTranslating cellular senescence research into clinical practice for metabolic disease
Chaib, S., Palmer, A. K., Wyles, S. P., Musi, N., Kirkland, J. L., & Tchkonia, T. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01187-9 · Cited by 17
“Although it is unclear whether cellular senescence in muscle directly contributes to age-related sarcopenia, studies indicate that removing senescent cells from progeroid mice can prevent progeria-related sarcopenia 68 .”
Self-citationMuscle metabolism in older adults
Иванникова, Е. В., Dudinskaya, Е. N., & Onuchina, Y. S. (2022) · Russian Journal of Geriatric Medicine · doi:10.37586/2686-8636-2-2022-96-102 · Cited by 10
Targeted Therapeutics Delivery by Exploiting Biophysical Properties of Senescent Cells
Low, J., Chan, B., & Tay, A. K. P. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202107990 · Cited by 11
Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice
Hashimoto, M., Goto, A., Endo, Y., Sugimoto, M., Ueda, J., & Yamashita, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031276 · Cited by 10
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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