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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- 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.
- Checkable: passes — It can be checked against evidence.
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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.
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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.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“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
“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
“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]
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
“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
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
“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]
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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InfluentialThe Molecular Response to Renal Injury
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Calcinosis: insights from other calcinoses
Tsakali, S. S., & Shanahan, C. M. (2020) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000746 · Cited by 5
Regenerative Potential Across Species: An Eco-Evo-Devo Perspective
Coffman, J. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814879-2.00008-x · Cited by 5
Mehmood, A., Xue, Y., Yassin, H. M., Zubair, M. A., Rahmat, S. A., & Ahmad, A. (2025) · Współczesna Onkologia · doi:10.5114/wo.2025.152369 · Cited by 5
“In opposing a number of aging phenotypes, including skeletal muscle atrophy [47], glomerulosclerosis of the kidney [48], and macrophage infiltration of tissues (a characteristic of chronic inflammation [45, 49]), thus longer-term treatments (20–26 months) can be successful.”
Senescence-Associated Chromatin Rewiring Promotes Inflammation and Transposable Element ActivationPreprint
Dalgarno, A., Evans, S. A., Kelsey, M. M. G., Nuñez, T. A., Rocha, A. V., Clark, K., Sedivy, J. M., & Neretti, N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.11.659151 · Cited by 5
“Studies in mice have also indicated that the clearance of senescent cells can extend lifespan and healthspan 7,8 .”
Recent advances in cell‐based and cell‐free therapeutic approaches for sarcopenia
Wu, S., Lin, S., Zhang, X., Alizada, M., Wang, L., Zheng, Y., Ke, Q., & Xu, J. (2022) · The FASEB Journal · doi:10.1096/fj.202200675r · Cited by 7
Cellular senescence as a source of chronic microinflammation that promotes the aging process
Nakanishi, M. (2025) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.101.014 · Cited by 5
“These models include INK-ATTAC mice, in which FK506-binding-protein–caspase 8 was inserted under control of the p16 gene promoter, 14),15),48)–51) 16-3MR mice in which the p16 promoter in the BAC cassette drives herpes simplex virus 1 thymidine kinase, and knock-in mouse models in which the exon of…”
News from the old: Aging features in the intracardiac, musculoskeletal, and enteric nervous systems
Haider, S., Sassu, E., Stefanovska, D., Stoyek, M. R., Preißl, S., & Hortells, L. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102690 · Cited by 7
Exercise Against Aging: Darwinian Natural Selection Among Fit and Unfit Cells Inside Human Body
Kuo, C. (2019) · Journal of Science in Sport and Exercise · doi:10.1007/s42978-019-0002-y · Cited by 5
“Recently, this idea has been supported by the evidence of extended lifespan through removing p16INK4a+ senescent cells in a small multicellular system [13].”
BackgroundBradley, J., O'Shea, P. J., Wrench, C., Mattsson, J., Paulin, R., Overed-Sayer, C. L., Rosenberg, L., Olsson, H., & Gianni, D. (2025) · SLAS DISCOVERY · doi:10.1016/j.slasd.2025.100223 · Cited by 5
INDUCTION OF EARLY PULMONARY SENESCENCE IN EXPERIMENTAL SEPSIS
Mösenlechner, M., Schlösser, D., Braumüller, S. T., Dörfer, L., Mannes, M., Kawach, R., Strauß, G., Schmidt, C. Q., Lupu, L., & Huber-Lang, M. S. (2024) · Shock · doi:10.1097/shk.0000000000002512 · Cited by 6
“Furthermore, those animals that were therapeutically cleared of these cells revealed a significant delay of age-related disorders (54,55).”
Bolden, J. E., & Lowe, S. W. (2015) · Elsevier eBooks · doi:10.1016/b978-1-4557-4066-6.00015-9 · Cited by 8
Fucoidans are senotherapeutics that enhance SIRT6-dependent DNA repairPreprint
Robbins, P. D., Zhang, L. J., Elsallabi, O., Soto-Palma, C., Bartz, J., Salekeen, R., Nunes, A., Xu, W., Lee, K., Hughes, B., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6613032/v1 · Cited by 6
Mini review: Gene therapy targets for aging-associated diseases
Shchukina, E., Eremin, I. I., Mazunin, I., & Alexey, M. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152708 · Cited by 5
Laisné, M., Rodgers, B., Benlamara, S., Wicinski, J., Nicolas, A., Djerroudi, L., Gupta, N., Ferry, L., Kirsh, O., Daher, D., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03002-7 · Cited by 6
“…cells, such as the upregulated genes ETV1 - a nuclear effector of Ras-Kinase signaling involved in cell proliferation and differentiation - [57, 58], PGHDH -an enzyme involved in glycolysis, upregulated in basal-like breast cancers [59]- and LMO4 -an inhibitor of mammary epithelial cell…”
BackgroundEstablishing evidence for immune surveillance of β-cell senescence
Morelli, N. R., Pipella, J., & Thompson, P. J. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.01.003 · Cited by 7
In vitro senescence and senolytic functional assays
Ryan, P., & Lee, J. (2025) · Biomaterials Science · doi:10.1039/d4bm01684j · Cited by 7
Cox, L. S. (2022) · The Journal of the Economics of Ageing · doi:10.1016/j.jeoa.2022.100423 · Cited by 6
Sun, Z., Jiang, W.-D., Lu, G., Ding, Y., Wang, L., Geng, J.-Y., Zhang, N., Wang, H., Kang, P., & Tang, B. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167863 · Cited by 5
The macromolecular machinery of the nucleus in the senescence process
Xavier, E. A. (2022) · World Journal of Advanced Research and Reviews · doi:10.30574/wjarr.2022.15.2.0844 · Cited by 6
Immune therapeutic strategies for the senescent tumor microenvironment
Yasuda, T., & Wang, Y. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02865-7 · Cited by 10
“The removal of p16 positive-senescent cells (senolysis) has been found to prevent or delay tissue dysfunction and extend lifespan of in vivo model [58 – 60].”
Senescence as a therapeutic target
Meyer, K. R., Lopez-Dominguez, J. A., Maus, M., Kovatcheva, M., & Serrano, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822514-1.00014-6 · Cited by 5
Identification of lipid senolytics targeting senescent cells through ferroptosis inductionPreprint
Zhang, L. J., Salekeen, R., Soto-Palma, C., Elsallabi, O., Ye, H., Hughes, B., Zhang, B., Nunes, A., Lee, K., Xu, W., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.14.618023 · Cited by 5
Terapias antienvejecimiento aplicadas a la enfermedad de Alzheimer
Abreu, G. S. A., Armas, J. M. B., & Fuentes, R. C. (2017) · Revista Española de Geriatría y Gerontología · doi:10.1016/j.regg.2017.02.007 · Cited by 6
“La rapamicina aumenta significativamente tanto la esperanza de vida como la de salud en ratones y diversos organismos simples como levaduras, gusanos o moscas 14 .”
Genetics of aging and longevity
Moskalev, A., Proshkina, E., Belyi, A. A., & Solovev, I. A. (2016) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vj16.171 · Cited by 6
Amram, S., Iram, T., Lazdon, E., Vassar, R. J., Ben‐Porath, I., & Frenkel, D. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/700013 · Cited by 7
“For example, progeria syndrome is associated with accelerated aging in children (7), and clearance of senescent cells in a progeria syndrome mouse model resulted in a rejuvenation of aged tissues, such as adipose tissue, skeletal muscle, and the eye (7).”
BackgroundOliveros, A., Poleschuk, M., Cole, P. D., Boison, D., & Jang, M. (2023) · International review of neurobiology · doi:10.1016/bs.irn.2023.08.003 · Cited by 6
Research progress on the role of extracellular vesicles derived from aging cells in osteoporosis
Chen, H., Huang, G., Mao, W., He, P., Hou, G., Zhang, W., Liu, Z., Li, A., & Qin, S. (2023) · Bioscience Reports · doi:10.1042/bsr20221775 · Cited by 5
Nakano, Y., & Johmura, Y. (2025) · The Journal of Biochemistry · doi:10.1093/jb/mvae098 · Cited by 7
Telomere in Aging and Age-Related Diseases
Meiliana, A., Dewi, N. M., & Wijaya, A. (2017) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v9i3.361 · Cited by 6
Cytokine-induced ‘bystander’ senescence in DDR and immuno-surveillance
Hodný, Z., Hubáčková, S., & Bártek, J. (2013) · Oncotarget · doi:10.18632/oncotarget.1487 · Cited by 5
Anti-ageing natural supplements: the main players in promoting healthy lifespan
Izadi, M., Sadri, N., Abdi, A., Zadeh, M. M. R., Jalaei, D., Ghazimoradi, M. M., Shouri, S., & Tahmasebi, S. (2024) · Nutrition Research Reviews · doi:10.1017/s0954422424000301 · Cited by 6
Modeling of senescent cell dynamics predicts a late‐life decrease in cancer incidence
Bieuville, M., Tissot, T., Robert, A., Henry, P., & Pavard, S. (2023) · Evolutionary Applications · doi:10.1111/eva.13514 · Cited by 4
“Besides, increasing evidence also shows that the accumulation of senescent cells in tissues is one of the causes of actuarial ageing and ultimately of body impairment, at least at old ages (Baker et al., 2011; He & Sharpless, 2017; López- Otín et al., 2013; van Deursen, 2014).”
BackgroundInfluentialImpact of Aging and Cellular Senescence in the Pathophysiology of Preeclampsia
Suvakov, S. R., Kattah, A. G., Gojković, T., Enninga, E. A. L., Pruett, J. E., Jayachandran, M., Sousa, C., Santos, J., Hassan, C. A., Suarez, M. L. G., et al. (2023) · Comprehensive physiology · doi:10.1002/cphy.c230003 · Cited by 6
Finding Shangri-La: Limiting the Impact of Senescence on Aging
Trabucco, S. E., & Zhang, H. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.02.002 · Cited by 5
“…induction to activate caspase and apoptosis selectively in p16-expressing senescent cells, Baker and colleagues recently showed that genetic clearance of senescent cells in mice delays and ameliorates certain age-associated debilitations and extends lifespan (Baker et al., 2011, 2016).”
BackgroundHautalterung – zelluläre Seneszenz
Scharffetter‐Kochanek, K., Wang, Y., Makrantonaki, E., Crișan, D., Wlaschek, M., Geiger, H., & Maity, P. (2023) · Die Dermatologie · doi:10.1007/s00105-023-05201-x · Cited by 5
Bramwell, L. R., Frankum, R., & Harries, L. W. (2024) · Cells · doi:10.3390/cells13060517 · Cited by 4
“Clearance of senescent cells significantly extends lifespan, improves mobility and fur condition in mouse models of progeria, and improves multiple aspects of functionality in aged wild-type mice [11–15].”
BackgroundMahoney, S. A., Darrah, M. A., Venkatasubramanian, R., Ciotlos, S., Rossman, M. J., Campisi, J., Seals, D. R., Melov, S., & Clayton, Z. S. (2025) · Aging Cell · doi:10.1111/acel.70118 · Cited by 6
“(Baker et al. 2011).”
γδ T Cells Target and Ablate Senescent Cells in Aging and Alleviate Pulmonary FibrosisPreprint
Meca-Laguna, G., Admasu, T. D., Shankar, A., Barkovskaya, A., Collibee, I., Krakauer, A. A., Tran, T., Rae, M. J., & Sharma, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.05.652251 · Cited by 5
Targeting Alternative Splicing for Reversal of Cellular Senescence in the Context of Aesthetic Aging
Bramwell, L. R., & Harries, L. W. (2020) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000007618 · Cited by 6
Senolysis and Senostasis Through the Plasma Membrane
Kim, K. M., Noh, J. H., & Gorospe, M. (2020) · Healthy ageing and longevity · doi:10.1007/978-3-030-44903-2_7 · Cited by 5
Cardiovascular Biomarkers and Their Utility in the Older Adult
Bell, S. P., Giuseffi, J., & Forman, D. E. (2012) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-012-0262-0 · Cited by 5
Procyanidin C1 is a natural agent with senolytic activity against aging and age-related diseasesPreprint
Xu, Q., Fu, Q., Li, Z., Liu, H., Wang, Y., Lin, X., He, R., Zhang, X., Campisi, J., Kirkland, J. L., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.14.439765 · Cited by 5
Self-citationWang, Y., Liang, W., Wang, T., Zhang, C., Yang, Y., Cong, C., Wang, X., Wang, S., Wang, D., Huo, D., et al. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.110792 · Cited by 5
“Transgenic mice with a mutant human SOD1 G93A gene (B6SJL-Tg (SOD1-G93A) 1Gur/J) over-expression (Baker et al., 2011) were acquired from Jackson Laboratory (Stock no. 002726; Bar Harbor, ME, USA).”
MethodAging is an adaptation that selects in animals against disruption of homeostasis
Muller, A. W. J. (2018) · Medical Hypotheses · doi:10.1016/j.mehy.2018.07.020 · Cited by 6
Tumor Dormancy, Quiescence, and Senescence, Volume 1
Hayat, M. A. (2013) · Springer eBooks · doi:10.1007/978-94-007-5958-9 · Cited by 6
p16-dependent upregulation of PD-L1 impairs immunosurveillance of senescent cellsPreprint
Majewska, J., Agrawal, A., Mayo, A., Roitman, L., Chatterjee, R., Kralova, J. S., Landsberger, T., Katzenelenbogen, Y., Meir-Salame, T., Hagai, E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.30.524522 · Cited by 5
“5 mg/ml; Sigma, #L2630) for 30 min, 3 times a week for 10 weeks, in a custombuilt cylindrical chamber as described previously (1, 2).”
BackgroundMethodLattice percolation approach to numerical modelling of tissue aging
Privman, V., Gorshkov, V., & Libert, S. (2015) · International Journal of Parallel Emergent and Distributed Systems · doi:10.1080/17445760.2015.1057588 · Cited by 5
The Biology of Aging: Implications for Diseases of Aging and Health Care in the Twenty‐First Century
Watt, D. F. (2014) · Wiley eBooks · doi:10.1002/9781118730676.ch1 · Cited by 4
Reduced Usage of GLS Intronic Polyadenylation Promotes Cellular Senescence
Li, X., Li, Y., Ding, D., Xie, B., Yao, J., Chen, Y., Zhao, Z., Yu, P., Zhang, S., Fu, Y., et al. (2025) · Phenomics · doi:10.1007/s43657-024-00198-2 · Cited by 4
“As dysregulated ROS level and insufficient energy generation of mito - chondria has been reported to induce senescence in various cell types (Baker et al. 2011; Campisi 2013 ), we quantified these two metabolites in GAC -KD cells.”
Fontanilla-Ramirez, P., Willaume, S., Thezé, B., Moussa, A., Pennarun, G., & Bertrand, P. (2020) · médecine/sciences · doi:10.1051/medsci/2020241 · Cited by 6
Exercise Interventions for the Management of Sarcopenia: Possibilities and Challenges
Edwards, H., Jones, H. S., Moseley, J., Marshall, T., El‐Khamisy, S. F., Aung, M. N., & Farrow, M. (2023) · Physical & Occupational Therapy In Geriatrics · doi:10.1080/02703181.2023.2220738 · Cited by 4
“65,66 Exercise has been shown to positively affect the regenerative capacity of aged muscles.”
BackgroundExtension of Life Span in Laboratory Mice
Unnikrishnan, A., Deepa, S. S., Herd, H. R., & Richardson, A. G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00019-1 · Cited by 7
Immunosuppressive macrophages determine the effect of cellular senescence on tumor progression
Lalinde-Gutiérrez, M., Pérez‐Ramos, S., Rodilla, V., Garcia-Baucells, P., Julia, P.-B., Berenguer‐Molins, P., Nonell, L., Agustí-Barea, I., Mueller, C. G., & Arribas, J. (2026) · Science Advances · doi:10.1126/sciadv.adx2988 · Cited by 4
“Many of them express reporters and/or factors that induce cell death under the control of the Cdkn2a/ p16 INK4a promoter ( 10 – 12 ).”
Oxidative Telomere Attrition, Nutritional Antioxidants and Biological Aging
Glade, M. J. (2015) · International Journal Of Nutrition · doi:10.14302/issn.2379-7835.ijn-14-606 · Cited by 3
The m⁶A epitranscriptome: A regulatory nexus linking cellular senescence and oncogenesis
Xu, Y., Zhou, X., Su, X., Xie, W., Huang, Z., Yu, S., Tan, J., He, J., & Zhang, J. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103032 · Cited by 5
New genetic and epigenetic approaches in gerontology
Баранов, В. С., Glotov, O. S., & Baranova, E. V. (2014) · Advances in Gerontology · doi:10.1134/s2079057014040055 · Cited by 4
“lengthening life expectancy [24].”
BackgroundTelomere elongation in the gut extends zebrafish lifespanPreprint
Maï, M. E., Guigonis, J., Pourchet, T., Kang, D., Yue, J., & Ferreira, M. G. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.10.475664 · Cited by 4
Borowik, A., Lawrence, M. M., Peelor, F. F., Piekarz, K. M., Crosswhite, A., Richardson, A. G., Miller, B. F., Remmen, H. V., & Brown, J. L. (2024) · GeroScience · doi:10.1007/s11357-024-01070-x · Cited by 4
“Baker et al. were the first to report that senescent cells accumulate in skeletal muscle [18].”
Kühnel, H., Pasztorek, M., Kuten-Pella, O., Kramer, K., Bauer, C., Lacza, Z., & Nehrer, S. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46030122 · Cited by 4
“Cellular senescence has emerged as a significant contributor to age-related degenerative diseases [1,2].”
BackgroundYu, X., Lobo, J. D., Sundermann, E. E., Baker, D. J., Tracy, R. P., Kuchel, G. A., Stephenson, K. E., Letendre, S. L., Brew, B. J., Cysique, L. A., et al. (2022) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2022.0079 · Cited by 6
“Using genetically engineered mouse models, we have demonstrated that senescent cells accumulate quickly in prematurely-aged mouse models, and that their subsequent attenuation or elimination can impact their health 10,11 and also positively influence aging in otherwise normal mice.”
Self-citationLi, J., Zhao, K., Yang, G., Lv, H., Zhang, R., Li, S., Chen, Z., Xu, M., Yang, N., & Dai, S. (2025) · Molecules · doi:10.3390/molecules30122653 · Cited by 4
“The selective removal of p16 high-expressing cells from progeroid mice improved their healthspan, extended the median lifespan, and delayed tumorigenesis [12].”
Stem Cell Senescence as the Memory of Past Injuries
Gianfranceschi, G., Gri, G., Cesselli, D., & Beltrami, A. P. (2015) · Current Pathobiology Reports · doi:10.1007/s40139-015-0071-5 · Cited by 4
Detection of Nuclear Envelope Alterations in Senescence
Bárcena, C., Osorio, F. G., & Freije, J. M. P. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-239-1_16 · Cited by 4
Chronic Kidney Disease and Cellular Senescence
Morevati, M., Tavenier, J., Scheibye‐Knudsen, M., Houlind, M. B., Hedayati, A., & Hornum, M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073205 · Cited by 4
“Furthermore, utilizing transgene INK-ATTAC technology to selectively eliminate p16-positive senescent cells through drug intervention has shown the potential to alleviate age-related traits, including preservation of kidney function, as well as extend healthspan [141,142].”
Khosla, S. (2024) · Journal of Clinical Investigation · doi:10.1172/jci180558 · Cited by 4
Recent Technological Innovations to Promote Cardiovascular Research
Yuasa, S. (2022) · Circulation Journal · doi:10.1253/circj.cj-21-0978 · Cited by 4
Srour, E., Martin, N., Drullion, C., de Schutter, C., Giroud, J., Pioger, A., Deslé, J., Saas, L., Nassour, J., Théry, J., et al. (2024) · Aging · doi:10.18632/aging.206149 · Cited by 4
Valerius, M. T. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2011111106 · Cited by 4
Lissa, D., Joruiz, S. M., Dranchak, P. K., Ungerleider, K., Yamada, L., Horikawa, I., Oliphant, E. N., Manubag, R., von Muhlinen, N., Beck, J. A., et al. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00186 · Cited by 5
Souza, T. B., & Baptista, R. R. (2023) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2023.1238500 · Cited by 4
“Senescent cells are less responsive to anti-in fl ammatory stimuli, including those potentially triggered by exercise (33).”
BackgroundGaray, R. P. (2024) · Exploration of Drug Science · doi:10.37349/eds.2024.00040 · Cited by 4
Mu, H., Gao, Y., Cao, G.-C., Jiang, J., Wang, H., & Zhao, W. (2022) · Fitoterapia · doi:10.1016/j.fitote.2022.105165 · Cited by 4
Khan, T., McFall, D. J., Hussain, A. I., Frayser, L. A., Casilli, T. P., Steck, M. C., Sánchez-Brualla, I., Kuehn, N. M., Cho, M., Barnes, J. A., et al. (2025) · Annals of Neurology · doi:10.1002/ana.78118 · Cited by 5
“7,13,28,49,50 Genetic SC ablation reduced daily seizure burden without affecting the duration of the seizures themselves.”
de Mendonça, L. B., Lenz, G., & Filippi‐Chiela, E. C. (2025) · Biochemical Society Transactions · doi:10.1042/bst20253054 · Cited by 5
“SnCs also affect pathological contexts such as chronic inflammation (inflammaging) [14–16], metabolic diseases [17,18], cancer [19], osteoarthritis [20], and others [21].”
Development of novel flavonoid senolytics through phenotypic drug screening and drug designPreprint
Zhang, L. J., Salekeen, R., Soto-Palma, C., He, Y., Elsallabi, O., Hughes, B., Nunes, A., Xu, W., Zhang, B., Mohamed, A. D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.27.620529 · Cited by 4
Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease
Kliment, C. R., Gurkar, A. U., Cárdenes, N., Ramonell, R. P., Finkel, T., & Königshoff, M. (2026) · Physiological Reviews · doi:10.1152/physrev.00024.2025 · Cited by 6
Brown adipose tissue: a potential target for aging interventions and healthy longevity
Li, H., Li, J., Song, C., Yang, H., Luo, Q., & Chen, M. (2024) · Biogerontology · doi:10.1007/s10522-024-10137-3 · Cited by 6
“The SASP can disrupt the tissue microenvironment and promote inflammation, thereby potentially exacerbating age-related pathologies (Campisi and d’Adda di Fagagna 2007; Baker et al. 2011).”
Ko, D., Mun, S., Kim, M., Nho, Y. H., Lee, D., Kang, S., Han, K., & Kim, M. (2024) · Advanced Biology · doi:10.1002/adbi.202300325 · Cited by 4
Proteolysis targeting chimeras as senolytics: An emerging senotherapy for combating aging
Cruickshank-Taylor, A. B., Kozora, J. S., Carew, J. S., Nawrocki, S. T., & Wang, W. (2025) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2025.103752 · Cited by 4
Kahraman, A. N., & Toklu, H. Z. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-84965-8_14 · Cited by 5
Cellular senescence: mechanisms and clinical implications
Михайловна, М. А., Pashenkov, M. V., & Pinegin, B. V. (2024) · Immunologiya · doi:10.33029/1816-2134-2024-45-2-221-234 · Cited by 10
The roles of cell cycle proteins in regulating the tumor immune microenvironment
Zhu, Q., Wei, X., Qu, Z., Lu, L., Zhang, Y., & Wang, H. (2025) · Genes & Diseases · doi:10.1016/j.gendis.2025.101706 · Cited by 6
“132,133 Haston et al 134 investigated the role of cells expressing p16 INK4a in the mouse NSCLC TME and the effect of these cells on tumor development.”
Aging skin and non-surgical procedures: a basic science overview
Vandiver, A. R., & Hogan, S. R. (2020) · Plastic and Aesthetic Research · doi:10.20517/2347-9264.2020.159 · Cited by 9
“In transgenic mouse models, the selective apoptosis of cells entering senescence prevents many aging phenotypes but imparts minimal effect on dermal thickness and also delays wound healing([109,110]).”
Background
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
About these checks
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.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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