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
“However, senescence has also been implicated both in promoting carcinogenesis 15 and in age-related pathologies 16,17 through its autocrine and paracrine effects, known as the senescence-associated secretory phenotype (SASP) originally described by the Campisi group.18,19”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“Using the Ink-Attac mouse model, in which a drug, AP20187 (AP), induces apoptosis through dimerization of FKBP-fused caspase 8, we previously discovered that clearance of p16-expressing cells improves parameters of physical health and function in progeroid mice31.”
From Cellular senescence mediates fibrotic pulmonary disease (2017) · cites this paper as [31]
The cited source says what the claim attributes to it.
In the citing paper
“Clearance of senescent cells is also beneficial for age-associated disorders 39 .”
From A complex secretory program orchestrated by the inflammasome controls paracrine senescence (2013) · cites this paper as [39]
The cited source says what the claim attributes to it.
In the citing paper
“elimination of senescent cells in an experimental progeria model delays age-related pathologies”
From The Hallmarks of Aging (2013) · cites this paper as Baker et al., 2011
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Longer term treatments (from 20 to 26 months of age) were effective at opposing several known phenotypes of aging: macrophage infiltration of tissues, a hallmark of chronic inflammation23,25, glomerulosclerosis of the kidney26 and skeletal muscle atrophy27 (Fig. 4e).”
From L1 drives IFN in senescent cells and promotes age-associated inflammation (2019) · cites this paper as [27]
Experimental — accuracy not yet measuredIn the citing paper
“Seminal discoveries, first by Hayflick and Moorehead, and lately by Baker et al., concretized cellular senescence as a major driver of aging with the age-associated accumulation of senescent cells”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Baker et al. 2011
In the citing paper
“and attenuation of age-related tissue dysfunction after their removal, even late in life (Hayflick and Moorhead 1961, Baker et al. 2011).”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Baker et al. 2011
In the citing paper
“Of note, we and our colleagues recently identified a possibly causal link between cellular senescence and aging phenotypes by showing that the clearance of senescent cells in a mouse progeroid model in vivo can delay age-related tissue dysfunction, including cataract formation, lipodystrophy, and lordokyphosis (7).”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“Experiments in progeroid INK-ATTAC;BubR1H/H mice showed that senescent cell clearance could reverse age-related lipodystrophy.”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“Current methods for assessing senescent cell burden in vivo are at the tissue level, either by quantification of senescent cells through methods such as immunohistochemistry for markers including heterochromatin foci, p16 expression, SA-βgal activity, or screening for transgenic labels such as the p16INK4A promoter-driven GFP in the INK-ATTAC mouse (7).”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“The development of transgenic mice from which senescent cells can be selectively cleared allowed the demonstration of senescent cells' causal role in disease (7).”
From Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity (2015) · cites this paper as [7]
In the citing paper
“Removal of senescent cells can attenuate age-related tissue dysfunction and extend health span.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Baker et al., 2011
In the citing paper
“selective elimination of senescent cells can prevent or delay age-related tissue dysfunction to extend life span and improve health span (Baker et al., 2011; Xu et al., 2015a; Baker et al., 2016; Hashimoto et al., 2016; Zhao et al., 2018).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Baker et al., 2011
In the citing paper
“Recently, attention has focused on the effect of senescence in vivo where purging p16-positive senescent cells in transgenic mice increased mean lifespan as well as aspects of healthspan65.”
From The central role of DNA damage in the ageing process (2021) · cites this paper as [65]
In the citing paper
“Another key feature of cellular senescence is the senescence-associated secretory phenotype (SASP), which is dependent on p38MAPK (p38 mitogen-activated protein kinases), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), cGAS(cyclic GMP-AMP synthase)/STING(stimulator of IFN genes), NOTCH and mTORmammalian target of rapamycin) signalling [38,39,40,41,42].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“Models of accelerated cellular senescence show premature ageing and increased incidence of age-related pathologies, suggesting that accumulating senescent cells contributes to ageing-related functional compromise and predisposes to age-related disease [38].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“Increased levels of p16INK4a have been documented in aged and stressed tissues, compared to younger, healthy tissues, whereas the removal of p16INK4a-expressing senescent cells in mice prevented or delayed tissue dysfunction and age-related disorders [38,80].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“progeroid models have provided in vivo experimental data of accelerated ageing-related degenerative pathologies.”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“In addition, experimental senolysis ameliorated ageing-related pathologies [38].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“Lifelong elimination of p16INK4A cells substantially delayed age-related disease, whereas late life elimination of p16INK4A cells attenuated these age-related pathologies [38]”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [38]
In the citing paper
“robust in vivo proof of the causative involvement of senescent cells in aging and in particular age-related diseases10,11.”
From Identification and characterization of Cardiac Glycosides as senolytic compounds (2019) · cites this paper as [11]
In the citing paper
“clearing senescent cells from progeroid or naturally aging mice improves healthspan 10, increases lifespan 12 and benefits an array of pathologies”
From Cardiac glycosides are broad-spectrum senolytics (2019) · cites this paper as [10]
In the citing paper
“Genetic and pharmacological strategies have demonstrated the benefits of eliminating senescent cells in the context of aging and disease 10,12,51.”
From Cardiac glycosides are broad-spectrum senolytics (2019) · cites this paper as [10]
In the citing paper
“To circumvent this problem, two similar yet unique mouse models have been developed to detect and eliminate senescent cells.”
From Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives (2018) · cites this paper as [29]
In the citing paper
“Using mouse models, elimination of these cells, through either genetic means or senolytic therapies, has largely shown beneficial impacts, irrespective of the disease or condition investigated (29-31, 99, 100).”
From Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives (2018) · cites this paper as [29]
In the citing paper
“In mice, the clearance of p16INK4A-positive cells extends lifespan and slows the emergence of ageing phenotypes and age-related functional deterioration of organs and tissues111,112.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [111]
In the citing paper
“It is thus not surprising that senescent cell burden is a good predictor of animal lifespan.94,95”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [94]
In the citing paper
“the clearance of senescent cells by either genetic engineering or the administration of senolytic drugs has been associated with reduced circulating levels of pro-inflammatory markers, increased lifespan, and delayed frailty-related phenotypes in mice”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [111]
In the citing paper
“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
“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]
Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · cited 1×
“After 48 h, cultures were fixed and stained for SA-b-Gal activity as describe”
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,379
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,070
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027 · cited 1×
“There were no overt side effects of senescent cell clearance in our model, even though it has been postulated that senescent cells enhance certain types of tissue repai”
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · cited 1×
“Additionally, the expression of p16 Ink4a is known to increase with ageing in several rodent and human tissue”
The Regulation of INK4/ARF in Cancer and Aging
Kim, W. Y., & Sharpless, N. E. (2006) · Cell · doi:10.1016/j.cell.2006.10.003 · Cited by 1,009
Jun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998 · cited 1×
“There were no overt side effects of senescent cell clearance in our model, even though it has been postulated that senescent cells enhance certain types of tissue repai”
A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow
Soleimani, M., & Nadri, S. (2009) · Nature Protocols · doi:10.1038/nprot.2008.221 · Cited by 920 · cited 1×
“Cell culture Culture of bone marrow cells was as previously describe”
Cited by
Sorted by citations
Items 1,201–1,300 of 3,753
Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain
Santoro, A., Spinelli, C. C., Martucciello, S., Nori, S. L., Capunzo, M., Puca, A. A., & Ciaglia, E. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0118-003r · Cited by 50
Liu, Y., Shi, Y., Liu, Y., Pan, X., & Zhang, K. (2018) · Acta Pharmacologica Sinica · doi:10.1038/s41401-018-0007-9 · Cited by 53
Elevated skin senescence in young mice causes delayed wound healing
Thanapaul, R. J. R. S., Shvedova, M., Shin, G. H., Crouch, J. D., & Roh, D. S. (2022) · GeroScience · doi:10.1007/s11357-022-00551-1 · Cited by 52
Altered endocytosis in cellular senescence
Shin, E., Soung, N., Schwartz, M. A., & Kim, E. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101332 · Cited by 52
“However, cellular senescence also contributes to aging-related diseases (Baker et al., 2011; Childs et al., 2015; He and Sharpless, 2017; Munoz-Espin and Serrano, 2014).”
Sessions, G. A., Copp, M. E., Liu, J., Sinkler, M. A., D’Costa, S., & Diekman, B. O. (2019) · The FASEB Journal · doi:10.1096/fj.201900815rr · Cited by 52
Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities
Ramasamy, T. S., Yee, Y. M., & Khan, I. M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.625497 · Cited by 52
Emerging rejuvenation strategies—Reducing the biological age
Zhang, B., Trapp, A., Kerepesi, C., & Gladyshev, V. N. (2021) · Aging Cell · doi:10.1111/acel.13538 · Cited by 53
“Using this model to clear senescent cells results in reversal of certain aging phenotypes in several tissues, including skeletal muscle and eyes (Baker et al., 2011).”
BackgroundPotential role of senescence in radiation-induced damage of the aged skeleton
Chandra, A., Park, S. S., & Pignolo, R. J. (2018) · Bone · doi:10.1016/j.bone.2018.12.006 · Cited by 53
MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Redox Control of Cell Senescence
Lettieri-Barbato, D., Aquilano, K., Punziano, C., Minopoli, G., & Faraonio, R. (2022) · Antioxidants · doi:10.3390/antiox11030480 · Cited by 51
“In particular, the double-strand DNA breaks initiate a DNA damage response (DDR), which if it becomes persistent converges on two DDR effectors: p53/p21 [7,48–50,62] and/or pRb/p16 [18,49,50] (Figure 3A).”
BackgroundAging and Options to Halt Declining Immunity to Virus Infections
Palacios-Pedrero, M. Á., Osterhaus, A. D. M. E., Becker, T., Elbahesh, H., Rimmelzwaan, G. F., & Saletti, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681449 · Cited by 55
Senescent Cell Depletion Through Targeting BCL-Family Proteins and Mitochondria
Fan, Y., Cheng, J., Zeng, H., & Shao, L. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.593630 · Cited by 52
“…age-related diseases, such as chronic pulmonary disease, chronic bone marrow injury, osteoarthritis, atherosclerosis, neurodegenerative disorders, chronic renal diseases, and diabetes (Childs et al., 2017; He and Sharpless, 2017; McHugh and Gil, 2018; Barnes et al., 2019; Docherty et al., 2019).”
BackgroundHypoxia Prevents Mitochondrial Dysfunction and Senescence in Human c-Kit+ Cardiac Progenitor Cells
Korski, K., Kubli, D. A., Wang, B. J., Khalafalla, F. G., Monsanto, M. M., Firouzi, F., Echeagaray, O., Kim, T.-Y., Adamson, R. M., Dembitsky, W. P., et al. (2019) · Stem Cells · doi:10.1002/stem.2970 · Cited by 52
IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway
Handayaningsih, A. E., Takahashi, M., Fukuoka, H., Iguchi, G., Nishizawa, H., Yamamoto, M., Suda, K., & Takahashi, Y. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.07.140 · Cited by 52
microRNA-141 regulates BMI1 expression and induces senescence in human diploid fibroblasts
Dimri, M., Carroll, J. D., Cho, J., & Dimri, G. P. (2013) · Cell Cycle · doi:10.4161/cc.26592 · Cited by 53
“It has been shown that the overexpression of BMI1 results in repression of tumor suppressor p16INK4a, which has emerged as a major regulator of aging and age-associated pathologies.(18) Overexpression of BMI1 results in bypass of senescence in most cells, and immortalization of certain epithelial cell types.”
BackgroundNelson, D. M., McBryan, T., Jeyapalan, J. C., Sedivy, J. M., & Adams, P. D. (2014) · AGE · doi:10.1007/s11357-014-9637-0 · Cited by 53
“However, senescence has also been implicated in the promotion of aging (Baker et al. 2011; Krtolica et al. 2001).”
BackgroundYan, Z., Yin, H., Brochhausen, C., Pfeifer, C., Alt, V., & Docheva, D. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00406 · Cited by 52
“Interestingly, reducing p16 expression might be a way to postpone tissue and organ aging (Baker et al., 2011).”
BackgroundCurrent Trends in Anti-Aging Strategies
Rosén, R., & Yarmush, M. L. (2023) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-120122-123054 · Cited by 56
Li, Z.-Y., Chen, Z., Zhang, T., Wei, C., & Shi, W. (2016) · Aging · doi:10.18632/aging.101050 · Cited by 54
“Cellular senescence is characterized by irreversible proliferative arrest and a series of morphological and functional alterations, and may further contribute to the decline in organ function and to reduced or lost vitality in organisms [7-9].”
Systemic DNA damage responses: organismal adaptations to genome instability
Ermolaeva, M., & Schumacher, B. (2014) · Trends in Genetics · doi:10.1016/j.tig.2013.12.001 · Cited by 51
“senescent cells, by linking the expression of the p16Ink4a senescence gene promoter with caspase expression, alleviated the degenerative phenotypes of the BubRl mice [41].”
BackgroundAging and Mesenchymal Stem Cells: Therapeutic Opportunities and Challenges in the Older Group
Chen, H., Liu, O., Chen, S., & Zhou, Y. (2021) · Gerontology · doi:10.1159/000516668 · Cited by 52
Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles
Santelli, A., Sun, I. O., Eirin, A., Abumoawad, A., Woollard, J. R., Lerman, A., Textor, S. C., Puranik, A. S., & Lerman, L. O. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.119.012584 · Cited by 50
Akkaoui, J., Yamada, C., Duarte, C. L., Ho, A., Vardar‐Şengül, S., Kawai, T., & Movilă, A. (2020) · GeroScience · doi:10.1007/s11357-020-00258-1 · Cited by 53
Walker, E. M., Cha, J., Tong, X., Guo, M., Liu, J.-H., Yu, S., Iacovazzo, D., Mauvais-Jarvis, F., Flanagan, S. E., Korbonits, M., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109813 · Cited by 48
Spontaneous Lung Fibrosis Resolution Reveals Novel Antifibrotic Regulators
Tan, Q., Link, P. A., Meridew, J. A., Pham, T. X., Caporarello, N., Ligresti, G., & Tschumperlin, D. J. (2021) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0396oc · Cited by 49
“Although recent studies have emphasized the role of apoptotic clearance of fibrogenic cells as a mechanism to terminate lung fibrosis (57, 58), our work highlights an accompanying prominent role for deactivation and provides a rich dataset from which to identify potential regulators of this deactivation process.”
BackgroundLiu, P., Tang, Q., Chen, M., Chen, W., Lu, Y., Liu, Z., & He, Z. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.589908 · Cited by 50
Senotherapeutics: Targeting senescent cells for the main age-related diseases
Boccardi, V., & Mecocci, P. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111526 · Cited by 52
The senescence-associated secretory phenotype: Fueling a wound that never heals
Pulido, T., Velarde, M. C., & Alimirah, F. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111561 · Cited by 54
Oxidative stress and cellular senescence: Roles in tumor progression and therapeutic opportunities
Jin, P., Feng, X., Huang, C., Li, J., Wang, H. Z., Wang, X., Li, L., & Ma, L. (2024) · MedComm – Oncology · doi:10.1002/mog2.70007 · Cited by 57
Distinct mechanisms mediating therapy-induced cellular senescence in prostate cancer
Kallenbach, J., Roozbahani, G. A., Horestani, M. H., & Baniahmad, A. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00941-0 · Cited by 51
The third path of tubulointerstitial fibrosis: aberrant endothelial secretome
Lipphardt, M., Song, J. W., Matsumoto, K., Dadafarin, S., Dihazi, H., Muller, G. A., & Goligorsky, M. S. (2017) · Kidney International · doi:10.1016/j.kint.2017.02.033 · Cited by 50
Targeting Cell Senescence for the Treatment of Age-Related Bone Loss
Pignolo, R. J., Samsonraj, R. M., Law, S. F., Wang, H., & Chandra, A. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00504-2 · Cited by 52
New insights into the role of cellular senescence and chronic wounds
Yang, H., Zhang, X., & Bo, X. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1400462 · Cited by 54
Senolytic-Mediated Elimination of Head and Neck Tumor Cells Induced Into Senescence by Cisplatin
Ahmadinejad, F., Bos, T., Hu, B., Britt, E., Koblinski, J. E., Souers, A. J., Leverson, J. D., Faber, A. C., Gewirtz, D. A., & Harada, H. (2021) · Molecular Pharmacology · doi:10.1124/molpharm.121.000354 · Cited by 55
“Senolytics are a relatively new class of drugs that have been shown to selectively induce cell death in senescent cells (Baker et al., 2011; Saleh, Carpenter, et al., 2020).”
BackgroundCao, H., Yang, P., Liu, J. S., Shao, Y. X., Li, H., Lai, P., Wang, H., Liu, A., Guo, B., Tang, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41858-7 · Cited by 54
“Cellular senescence has emerged as a primary cause and an attractive therapeutic target of aging-associated chronic diseases, including OA 25,26 .”
Molecular pathology of rare progeroid diseases
Rieckher, M., Garinis, G. A., & Schumacher, B. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.06.011 · Cited by 50
FOXA1 mediates p16INK4a activation during cellular senescence
Li, Q., Zhang, Y., Fu, J., Han, L., Xue, L., Lv, C., Wang, P., Li, G., & Tong, T. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.35 · Cited by 50
“…1 February 2013; published online: 26 February 2013 The EMBO Journal (2013) 32, 858–873 www.embojournal.org EMBO THE JOURNAL 858 The EMBO Journal VOL 32 | NO 6 | 2013 &2013 European Molecular Biology Organization 2004; Lee et al, 2005; Wan et al, 2005; Gao et al, 2008; Augello et al, 2011).”
Backgroundp53 induces senescence through Lamin A/C stabilization-mediated nuclear deformation
Yoon, M.-H., Kang, S., Lee, S. J., Woo, T., Oh, A.-Y., Park, S., Ha, N., & Park, B.-J. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1378-7 · Cited by 52
Urolithin A attenuates auditory cell senescence by activating mitophagy
Cho, S. I., Jo, E.-R., & Song, H. S. (2022) · Scientific Reports · doi:10.1038/s41598-022-11894-2 · Cited by 54
The Multifaceted Role of Endothelial Sirt1 in Vascular Aging: An Update
Campagna, R., Mazzanti, L., Pompei, V., Alia, S., Vignini, A., & Emanuelli, M. (2024) · Cells · doi:10.3390/cells13171469 · Cited by 59
“Cellular senescence is causally involved in inducing age-related phenotype and thus it should not surprise that removing senescent cells counteracts or delays tissue dysfunction and prolongs lifespan [151].”
BackgroundSenescence in Pulmonary Fibrosis: Between Aging and Exposure
Venosa, A. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.606462 · Cited by 51
Long Noncoding Competing Endogenous RNA Networks in Age-Associated Cardiovascular Diseases
Greco, S., Gaetano, C., & Martelli, F. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20123079 · Cited by 51
Liu, Y., Lomeli, I., & Kron, S. J. (2024) · Cells · doi:10.3390/cells13151281 · Cited by 74
“Confirming these deleterious effects, genetic elimination of SnCs was shown to delay spontaneous tumorigenesis and decrease cancer-related mortality [19–22].”
BackgroundRole of lncRNAs in Cellular Aging
Degirmenci, U., & Sun, L. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00151 · Cited by 49
“Proc Natl Acad Sci U S A (2009) 106(23):9430–4.”
Kiss, T., Nyúl‐Tóth, Á., Gulej, R., Tarantini, S., Csípő, T., Mukli, P., Ungvari, A., Balasubramanian, P., Yabluchanskiy, A., Benyó, Z., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00519-1 · Cited by 48
Biphasic Modeling of Mitochondrial Metabolism Dysregulation during Aging
Baker, D. J., & Peleg, S. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.06.005 · Cited by 48
Self-citationAging, senescence and mitochondria: the PGC-1/ERR axis
Vernier, M., & Giguère, V. (2020) · Journal of Molecular Endocrinology · doi:10.1530/jme-20-0196 · Cited by 52
“As a proof of concept, clearance of senescent cells in a transgenic mouse model of premature aging attenuated age-related pathologies (Baker et al. 2011).”
BackgroundTherapeutic opportunities for senolysis in cardiovascular disease
Sweeney, M. D., Cook, S. A., & Gil, J. (2022) · FEBS Journal · doi:10.1111/febs.16351 · Cited by 54
Marcoux, S., Lê, O., Langlois-Pelletier, C., Laverdière, C., Hatami, A., Robaey, P., & Beausejour, C. M. (2013) · Radiation Oncology · doi:10.1186/1748-717x-8-252 · Cited by 49
“Moreover, clearance of p16 positive cells delays some agingassociated disorders [17].”
Cancer Response to Therapy-Induced Senescence: A Matter of Dose and Timing
Mongiardi, M. P., Pellegrini, M., Pallini, R., Levi, A., & Falchetti, M. L. (2021) · Cancers · doi:10.3390/cancers13030484 · Cited by 49
Despars, G., Carbonneau, C. L., Bardeau, P., Coutu, D. L., & Beausejour, C. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073206 · Cited by 49
“Given the growing body of evidence showing the deleterious physiological effect of senescent cell accumulation [14], a better understanding of the impact of senescence on bone homeostasis will help in the design of better treatments to alleviate bone dysfunction and other disabilities often observed in aged or irradia…”
BackgroundAnti-ageing effects of ubiquinone and ubiquinol in a senescence model of human dermal fibroblasts
Marcheggiani, F., Kordes, S., Cirilli, I., Orlando, P., Silvestri, S., Vogelsang, A., Möller, N., Blatt, T., Weise, J. M., Damiani, E., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.01.032 · Cited by 48
The complex interplay between aging and cancer
Trastus, L. A., & di Fagagna, F. D. (2025) · Nature Aging · doi:10.1038/s43587-025-00827-z · Cited by 56
“Ionizing radiation, UV light, genotoxic chemicals ...”
Senescence and Apoptosis: Architects of Mammalian Development
Wanner, E., Thoppil, H., & Riabowol, K. T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.620089 · Cited by 52
Gut-specific telomerase expression counteracts systemic aging in telomerase-deficient zebrafish
Maï, M. E., Bird, M., Allouche, A., Targen, S., Şerifoğlu, N., Lopes-Bastos, B., Guigonis, J., Kang, D., Pourcher, T., Yue, J., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00401-5 · Cited by 59
Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics
Saito, Y., & Chikenji, T. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.739510 · Cited by 53
Are skin senescence and immunosenescence linked within individuals?
Waaijer, M. E. C., Goldeck, D., Gunn, D. A., van Heemst, D., Westendorp, R. G. J., Pawelec, G., & Maier, A. B. (2019) · Aging Cell · doi:10.1111/acel.12956 · Cited by 48
Synergism of BCL-2 family inhibitors facilitates selective elimination of senescent cells
Rysanek, D., Vašicová, P., Kolla, J. N., Sedlák, D., Anděra, L., Bártek, J., & Hodný, Z. (2022) · Aging · doi:10.18632/aging.204207 · Cited by 48
Takeshita, H., Yamamoto, K. I., Nozato, S., Takeda, M., Fukada, S., Inagaki, T., Tsuchimochi, H., Shirai, M., Nozato, Y., Fujimoto, T., et al. (2018) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12334 · Cited by 49
PAI-1 contributes to homocysteine-induced cellular senescence
Sun, T., Ghosh, A. K., Eren, M., Miyata, T., & Vaughan, D. E. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.109394 · Cited by 49
Selective ablation of primary and paracrine senescent cells by targeting iron dyshomeostasis
Admasu, T. D., Kim, K., Rae, M. J., Avelar, R. A., Gonciarz, R. L., Rebbaa, A., de Magalhães, J. P., Renslo, A. R., Stolzing, A., & Sharma, A. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112058 · Cited by 49
“6 12 Drugs that selectively destroy SCs (senolytics) have been shown to extend healthy lifespan 8,13 and to delay, ameliorate, or in some respects reverse multiple age-related diseases in animal models and human studies, which supports a causal link between SC burden and various age-related…”
BackgroundThe Clearance Effect of Tetrahedral DNA Nanostructures on Senescent Human Dermal Fibroblasts
Mao, C., Pan, W., Shao, X., Ma, W., Zhang, Y., Zhan, Y., Gao, Y., & Lin, Y. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.8b20530 · Cited by 48
Nidadavolu, L. S., Niedernhofer, L. J., & Khan, S. A. (2013) · Aging · doi:10.18632/aging.100571 · Cited by 50
Lewińska, A., Radoń, A., Gil, K., Błoniarz, D., Ciuraszkiewicz, A., Kubacki, J., Kądziołka-Gaweł, M., Łukowiec, D., Gębara, P., Krogul-Sobczak, A., et al. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.3c17418 · Cited by 48
Transient metabolic improvement in obese mice treated with navitoclax or dasatinib/quercetin
Sierra‐Ramírez, A., López-Aceituno, J. L., Costa‐Machado, L. F., Plaza, A., Barradas, M., & Fernández-Marcos, P. J. (2020) · Aging · doi:10.18632/aging.103607 · Cited by 52
“Baker and collaborators demonstrated for the first time that removal of senescent cells is beneficial for age-related diseases, using a mouse model that specifically eliminates Cdkn2a-p16-positive cells, named INK-ATTAC [15].”
BackgroundMolecular mechanisms of ageing and related diseases
Liu, J. (2014) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12247 · Cited by 50
“Cell senescence also instigates organ and organism ageing, and removal of senescent cells from tissues delays tissue dysfunction and extends the health span of animals.(32)”
BackgroundHampel, H. J., Lista, S., Néri, C., & Vergallo, A. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101662 · Cited by 47
From cellular senescence to age-associated diseases: the miRNA connection
Schraml, E., & Grillari, J. (2012) · Longevity & Healthspan · doi:10.1186/2046-2395-1-10 · Cited by 47
“However, by removal of senescent cells the onset of cataract formation was significantly delayed, emphasizing the importance of senescence in this regard [27,28] as well as by hTERT gene therapy [32].”
BackgroundInfluentialTelomerase gene therapy: a novel approach to combat aging
Boccardi, V., & Herbig, U. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201200246 · Cited by 48
“Indeed, preventing the accumulation of senescent cells in aging mice significantly improves health-span, demonstrating that cellular senescence, regardless of its induction, is a cause of aging associated disorders (Baker et al, 2011).”
p16INK4A Influences the Aging Phenotype in the Living Skin Equivalent
Adamus, J. E., Aho, S., Meldrum, H., Bosko, C. A., & Lee, J.-M. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.468 · Cited by 48
“Moreover, p16INK4A has continued to gain strong support as an important component of the aging process (Sharpless, 2004; Campisi and d’Adda di Fagagna, 2007; Baker et al., 2011).”
BackgroundCellular Senescence and Periodontitis: Mechanisms and Therapeutics
Chen, S., Zhou, D., Liu, O., Chen, H., Wang, Y., & Zhou, Y. (2022) · Biology · doi:10.3390/biology11101419 · Cited by 51
VEGF receptor‐1 modulates amyloid β 1–42 oligomer‐induced senescence in brain endothelial cells
Angom, R. S., Wang, Y., Wang, E., Pal, K., Bhattacharya, S., Watzlawik, J. O., Rosenberry, T. L., Das, P., & Mukhopadhyay, D. (2018) · The FASEB Journal · doi:10.1096/fj.201802003r · Cited by 49
Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence
Abdelgawad, I. Y., Sadak, K. T., Lone, D. W., Dabour, M. S., Niedernhofer, L. J., & Zordoky, B. N. M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107751 · Cited by 47
Hypoxia/reoxygenation activates the JNK pathway and accelerates synovial senescence
Zhang, Y., Zhou, S., Cai, W., Han, G., Li, J., Chen, M., & Li, H. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11102 · Cited by 47
Frailty in mouse ageing: A conceptual approach
von Zglinicki, T., Varela‐Nieto, I., Brites, D. M. T. O., Karagianni, N., Ortolano, S., Georgopoulos, S., Cardoso, A. L., Novella, S., Lepperdinger, G., Trendelenburg, A., et al. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.07.004 · Cited by 46
Pleiotropic actions of estrogen: a mitochondrial matter
Velarde, M. C. (2012) · Physiological Genomics · doi:10.1152/physiolgenomics.00155.2012 · Cited by 50
“In fact, ablation of senescent cells can reduce the accelerated aging-related pathologies in a progeroid mouse model (4).”
BackgroundDai, H., Chen, R., Gui, C., Tao, T., Ge, Y., Zhao, X., Qin, R., Yao, W., Gu, S., Jiang, Y., et al. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01708-5 · Cited by 47
Crosstalk between gut microbiota and cellular senescence: a vicious cycle leading to aging gut
Kawamoto, S., & Hara, E. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.12.004 · Cited by 47
Brauer, E., Lange, T., Keller, D., Görlitz, S., Cho, S., Keye, J., Gossen, M., Petersen, A., & Kornak, U. (2022) · Aging Cell · doi:10.1111/acel.13744 · Cited by 50
“Elimination of these cells can delay the onset of these diseases (Baker et al., 2011) and even revert age- related tissue degeneration (Farr et al., 2017).”
Backgroundp16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses
Wang, Y., Sharpless, N. E., & Chang, S. S. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69574 · Cited by 49
“The accumulation of p16 (41).”
Berent-Maoz, B., Montecino-Rodriguez, E., Signer, R. A. J., & Dorshkind, K. (2012) · Blood · doi:10.1182/blood-2011-12-400002 · Cited by 46
Senescence and the Pro-tumorigenic Stroma
Alspach, E., Fu, Y., & Stewart, S. A. (2013) · Critical Reviews in Oncogenesis · doi:10.1615/critrevoncog.2014010630 · Cited by 47
Mouse Models of Accelerated Cellular Senescence
Yousefzadeh, M. J., Melos, K. I., Angelini, L. A., Burd, C. E., Robbins, P. D., & Niedernhofer, L. J. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8931-7_17 · Cited by 48
“It took five more years for similar results to be shown in wild-type mice (Baker et al., 2011; Baker et al., 2016).”
ResultInflammatory priming predisposes mice to age-related retinal degeneration
Mustafi, D., Maeda, T., Kohno, H., Nadeau, J. H., & Palczewski, K. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64427 · Cited by 46
“Conversely, adequate clearance of such cells can delay the onset of age-related tissue pathology (5).”
Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration
Salinas-Saavedra, M., Febrimarsa, Krasovec, G., Horkan, H. R., Baxevanis, A. D., & Frank, U. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112687 · Cited by 45
The role of cellular senescence in aging through the prism of Koch-like criteria
Yanai, H., & Fraifeld, V. E. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.004 · Cited by 45
Regulatory mechanisms and clinical manifestations of musculoskeletal aging
Grote, C. W., Reinhardt, D., Zhang, M., & Wang, J. (2019) · Journal of Orthopaedic Research® · doi:10.1002/jor.24292 · Cited by 57
“The removal of senescent cells in transgenic mice is associated with an increased lifespan and reduced morbidity, highlighting their role in aging.(54)”
BackgroundSubcellular structure, heterogeneity, and plasticity of senescent cells
Bitencourt, T. C., Vargas, J. E., Silva, A. O., Fraga, L. R., & Filippi‐Chiela, E. C. (2024) · Aging Cell · doi:10.1111/acel.14154 · Cited by 46
“…helpful roles in physiological processes like wound heal - ing (Demaria et al., 2014 ) and embryonic development (Storer et al., 2013 ), their accumulation in aging and aging-associated diseases contributes to loss of tissue function (Baker et al., 2011; Chang et al., 2016; Ogrodnik et al., 2021).”
BackgroundAnimal and human models to understand ageing
Lees, H., Walters, H., & Cox, L. S. (2016) · Maturitas · doi:10.1016/j.maturitas.2016.06.008 · Cited by 50
Ding, C., Min, J., Tan, Y., Zheng, L., Ma, R., Zhao, R., Zhao, H., Ding, Q., Chen, H., & Huo, D. (2024) · Advanced Materials · doi:10.1002/adma.202401361 · Cited by 49
Ezure, T., Sugahara, M., & Amano, S. (2019) · BioFactors · doi:10.1002/biof.1512 · Cited by 47
“Indeed, removal of senescent cells has been reported to improve agingassociated disorders in a mousemodel.(6) The presence of an aging-induced factor was demonstrated by means of parabiosis experiments.”
BackgroundKeeping zombies alive: The ER-mitochondria Ca2+ transfer in cellular senescence
Ahumada-Castro, U., Puebla-Huerta, A., Cuevas-Espinoza, V., Lovy, A., & Cárdenas, C. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119099 · Cited by 45
Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies
Cha, J., Aguayo‐Mazzucato, C., & Thompson, P. J. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1212716 · Cited by 52
“This model incorporates the promoter region of p16 to drive expression of a drugactivated apoptosis gene (FKBP8-Caspase8) selective in p16expressing senescent cells (6) and has been widely used as an in vivo reporter and genetic tool to deplete p16-expressing senescent”
BackgroundMethodImpact of aging on bone, marrow and their interactions
Hoffman, C. M., Han, J., & Calvi, L. M. (2018) · Bone · doi:10.1016/j.bone.2018.07.012 · Cited by 48
Targeting CDK4/6 for Anticancer Therapy
Qi, J., & Ouyang, Z. (2022) · Biomedicines · doi:10.3390/biomedicines10030685 · Cited by 49
“It has been shown in a mouse model that therapeutic interventions to clear senescent cells improve lifespan [68].”
BackgroundOxidative stress and cell senescence as drivers of ageing: Chicken and egg
von Zglinicki, T. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102558 · Cited by 57
Inflammaging, cellular senescence, and cognitive aging after traumatic brain injury
Lu, Y., Jarrahi, A., Moore, N. D., Bartoli, M., Brann, D. W., Baban, B., & Dhandapani, K. M. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106090 · Cited by 52
“Interestingly, genetic elimination of as few as 30% of p16 INK4a positive senescent cells delayed the onset of aging-associated phenotypes and extended the healthy lifespan of progeroid mice (Zhu et al., 2015; Baker et al., 2011; Farr et al., 2017).”
Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction
Jia, D., Tian, Z., & Wang, R. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102087 · Cited by 50
Mechanisms driving the ageing heart
Anderson, R., Richardson, G. D., & Passos, J. F. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.015 · Cited by 47
“and pharmacological clearance of senescent cells has been shown to ameliorate several age-related pathologies in different disease models and increase lifespan and healthspan in wild-type mice(Baar et al., 2017; Baker et al., 2016; Baker et al., 2011; Chang et al., 2016; Roos et al., 2016; Xu et al., 2015).”
González-Meljem, J. M., & Martínez-Barberá, J. P. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03798-7 · Cited by 48
A tale of the good and bad: Cell senescence in bone homeostasis and disease
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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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