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.
Overview
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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
9 of 19 cited sources checked · 5 supported · 0 flagged · 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data indicate that senescent cells were cleared from tissues and that this delays acquisition of age-related dysfunction in BubR1 hypomorphic mice.”
§ Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“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
“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
“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
“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
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]
Citations
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
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“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
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Four faces of cellular senescence
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The essence of senescence: Figure 1.
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Senescence of Activated Stellate Cells Limits Liver Fibrosis
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“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
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“Additionally, the expression of p16 Ink4a is known to increase with ageing in several rodent and human tissue”
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“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”
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Items 601–700 of 3,753
Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes
Wang, T., Notta, F., Navab, R., Joseph, J., Ibrahimov, E., Xu, J., Zhu, C.-Q., Borgida, A., Gallinger, S., & Tsao, M.-S. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0192 · Cited by 123
“Cell lines, tissue, and mouse strains This study was approved by the Research Ethics Board of the UniversityHealthNetwork (13-6377).”
BackgroundMethodSenotherapeutics: targeting senescence in idiopathic pulmonary fibrosis
Merkt, W., Bueno, M., Mora, A. L., & Lagares, D. (2020) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.12.008 · Cited by 119
Mouse Models to Disentangle the Hallmarks of Human Aging
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“Among them, the cardiovascular phenotype observed in Bub1b mice, which includes reduced number of vascular smooth muscle cells, increased fibrosis, and arterial wall stiffening, has been considered as the main cause of death of these mice.(25,26) Mutation in Bub1b has also been found in patients with Mosaic variegated…”
BackgroundMethodActivation of Lung p53 by Nutlin-3a Prevents and Reverses Experimental Pulmonary Hypertension
Mouraret, N., Marcos, É., Abid, S., Gary‐Bobo, G., Saker, M., Houssaini, A., Dubois‐Randé, J., Boyer, L., Boczkowski, J., Dérumeaux, G., et al. (2013) · Circulation · doi:10.1161/circulationaha.113.002434 · Cited by 129
“Whether this may occur in response to Nutlin treatment may depend on various factors such as age, immune system performance, and environmental conditions.(38) Thus, inducing cell senescence might hold promise as a treatment against pulmonary vascular remodeling, provided the senescent cells are simultaneously cleared…”
BackgroundZhao, J., Zhang, L., Lu, A., Han, Y., Colangelo, D., Bukata, C., Scibetta, A., Yousefzadeh, M. J., Li, X., Gurkar, A. U., et al. (2020) · Aging · doi:10.18632/aging.102863 · Cited by 122
“transgenic mice expressing an inducible apoptotic transgene from the p16 promoter leads to an extension of healthspan [2, 3].”
BackgroundLipids as Regulators of Cellular Senescence
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“Consistent with p16 being a major player in cellular senescence, genetic ablation of p16-positive cells, using the INK-ATTAC (Baker et al., 2011) and p16-3MR mice (Demaria et al., 2014), reduced senescent cell burden and improved healthspan, both in a progeria model, as well as naturally aged WT animals.”
MethodDeterioration of nuclear morphology and architecture: A hallmark of senescence and aging
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“Senescent cells accumulate in multiple tissues with age [5], and removal of these cells delays tumorigenesis and age-related disorders in different tissues [6] as well as prolongs lifespan in vivo [7].”
BackgroundFarr, J. N., Rowsey, J. L., Eckhardt, B. A., Thicke, B. S., Fraser, D. G., Tchkonia, T., Kirkland, J. L., Monroe, D. G., & Khosla, S. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3729 · Cited by 127
Self-citationNew Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death
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Social stress shortens lifespan in mice
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“For example, the ablation of senescent cells using the INK-ATTAC or the p16-3MR technologies, pharmacologically targeting the Ink4a transcriptionally active promoter in senescent cells, extended lifespan and improved healthspan in mice (Baker et al., 2011, 2016; Childs et al., 2016).”
MethodCellular senescence and cardiovascular diseases: moving to the “heart” of the problem
Evangelou, K., Vasileiou, P. V. S., Papaspyropoulos, A., Hazapis, O. G., Petty, R., Demaria, M., & Gorgoulis, V. G. (2022) · Physiological Reviews · doi:10.1152/physrev.00007.2022 · Cited by 127
Extracellular Vesicles as New Players in Cellular Senescence
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“The presence and age-dependent accumulation of senescent cells in aged tissues has been demonstrated [5], and convincing evidence has been provided that such accumulation can accelerate the decline of tissue functions and promote age-associated diseases [6–8].”
BackgroundCellular senescence, senescence-associated secretory phenotype, and chronic kidney disease
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Stressing the cell cycle in senescence and aging
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Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions
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“Clinical trials are now investigating strategies for treating dementia and physical frailty (Baker et al., 2011; Sha et al., 2019; Tompkins et al., 2017; Woo et al., 2019).”
Chandra, A., Lagnado, A. B., Farr, J. N., Doolittle, M., Tchkonia, T., Kirkland, J. L., LeBrasseur, N. K., Robbins, P. D., Niedernhofer, L. J., Ikeno, Y., et al. (2022) · Aging Cell · doi:10.1111/acel.13602 · Cited by 120
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“An even stronger argument was presented by Baker et al. (2011), who showed signs of reversion of several traits of progeroid phenotypes of mutant mice following pharmacological eradication of accumulated senescent cells expressing p16INK4a.”
BackgroundFarr, J. N., Atkinson, E. J., Achenbach, S. J., Volkman, T. L., Tweed, A. J., Vos, S. J., Ruan, M., Sfeir, J., Drake, M. T., Saul, D., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03096-2 · Cited by 127
“Moreover, the demonstration in old mice that clearing senescent cells using a genetic approach extended health span and lifespan 4,5 generated intense interest in therapeutically targeting senescent cells in humans to prevent or delay age-related comorbidities as a group 6 .”
Self-citationCapurso, C. A., Bellanti, F., Buglio, A. L., & Vendemiale, G. (2019) · Nutrients · doi:10.3390/nu12010035 · Cited by 124
Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain
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PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders
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Age Related Osteoporosis: Targeting Cellular Senescence
Föger‐Samwald, U., Kerschan‐Schindl, K., Butylina, M., & Pietschmann, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052701 · Cited by 121
“Elimination of senescent cells by a genetic approach in aged mice [35,42] led to the aim of therapeutically targeting the detrimental effects of senescence.”
BackgroundThe road ahead for health and lifespan interventions
Gonzalez-Freire, M., Diaz-Ruiz, A., Hauser, D., Martinez-Romero, J., Ferrucci, L., Bernier, M., & de Cabo, R. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101037 · Cited by 118
“The clearance of p16Ink4a-positive senescent cells delays age-related disorders (Baker et al., 2011) and evidence suggests that genes implicated in cellular senescence are also linked to longevity and age-related diseases (Tacutu et al., 2011).”
BackgroundBelle, J. I., Sen, D., Baer, J. M., Liu, X., Lander, V. E., Ye, J., Sells, B. E., Knolhoff, B. L., Ahmad, F. F., Kang, L., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0428 · Cited by 124
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Of Flies, Mice, and Men: Evolutionarily Conserved Tissue Damage Responses and Aging
Neves, J., Demaria, M., Campisi, J., & Jasper, H. (2015) · Developmental Cell · doi:10.1016/j.devcel.2014.11.028 · Cited by 119
“In support of this hypothesis, eliminating senescent cells prevents or delays the onset of some age-related pathologies in a mouse model of accelerated aging (Baker et al., 2011).”
BackgroundInfluentialGuo, Y., Xue, L., Tang, W., Xiong, J., Chen, D., Dai, Y., Wu, C., Wei, S., Dai, J. Y., Wu, M., et al. (2024) · Human Reproduction Update · doi:10.1093/humupd/dmae020 · Cited by 136
“Senolytics have emerged as promising agents for selectively targeting senescent cells through the activation of ‘suicide’ genes and the modulation of various cellular pathways (Baker et al. , 2011).”
BackgroundRegulation of cellular senescence via the FOXO 4‐p53 axis
Bourgeois, B. M. R., & Madl, T. (2018) · FEBS Letters · doi:10.1002/1873-3468.13057 · Cited by 124
Targeting aging for disease modification in osteoarthritis
Collins, J. A., Diekman, B. O., & Loeser, R. F. (2017) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000456 · Cited by 117
Antignano, I., Liu, Y., Offermann, N., & Capasso, M. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04775-y · Cited by 117
“, microglia) but affects the whole body, cell-specific targeting strategies, in combination with or without senescence-targeting transgenic mouse models [79, 89, 90], would help clarify the specific role of senescent microglia.”
BackgroundEntringer, S., Buß, C., & Wadhwa, P. D. (2012) · Science Signaling · doi:10.1126/scisignal.2003580 · Cited by 121
Yabluchanskiy, A., Tarantini, S., Balasubramanian, P., Kiss, T., Csípő, T., Fülöp, G., Lipécz, Á., Ahire, C., DelFavero, J., Nyúl‐Tóth, Á., et al. (2020) · GeroScience · doi:10.1007/s11357-020-00154-8 · Cited by 124
“…cyclin-dependent kinase inhibitor p16INK4A in genetically modified mice prolongs median lifespan and improves overall health (Farr et al. 2017; Baker et al. 2011; Baker et al. 2016; 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;…”
BackgroundVasko, R., Xavier, S., Chen, J., Lin, C. H. S., Ratliff, B. B., Rabadi, M. M., Maizel, J., Tanokuchi, R., Zhang, F., Cao, J., et al. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013010069 · Cited by 118
Dellago, H., Preschitz‐Kammerhofer, B., Terlecki‐Ζaniewicz, L., Schreiner, C., Fortschegger, K., Chang, M. W. ‐., Hackl, M., Monteforte, R., Kühnel, H., Schosserer, M., et al. (2013) · Aging Cell · doi:10.1111/acel.12069 · Cited by 121
“This view is supported by the findings that removal of senescent cells (Baker et al., 2011) or re-elongation of telomeres (Jaskelioff et al.”
BackgroundGaikwad, S., Senapati, S., Haque, M. A., & Kayed, R. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13490 · Cited by 117
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“Remarkably, the use of progeroid mouse models has provided evidence that ablation of p16 cells improves many of these disease symptoms, reinforcing a detrimental role of SCs in aged tissues (Baker et al., 2011; Rhinn et al., 2019).”
BackgroundCellular senescence: Neither irreversible nor reversible
Reimann, M., Lee, S., & Schmitt, C. A. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20232136 · Cited by 125
“” Senolysis has been introduced as a prime therapeutic strategy to extend a healthy lifespan by delaying features of pathologic aging and to prevent detrimental implications related to long-term-arrested cancer cells (Baker et al., 2011, 2016; D¨orr et al., 2013; Xu et al., 2018).”
BackgroundSystemic DNA damage responses in aging and diseases
Ribezzo, F., Shiloh, Y., & Schumacher, B. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.12.005 · Cited by 116
“Intriguingly, elimination of senescent cells in these mice by expressing a caspase-8 transgene under the control of a p16Ink4a promoter attenuated the aging phenotype [96].”
The great unravelling: chromatin as a modulator of the aging process
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“Eliminating p16INK4A-positive cells throughout life delayed the onset of age-related tissue degeneration and led to lifespan extension, but doing so only in aged adult mice also delayed and improved the manifest traits of aging [10].”
BackgroundNoncoding RNA in age-related cardiovascular diseases
Greco, S., Gorospe, M., & Martelli, F. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.01.011 · Cited by 119
“age-related physiologic and pathologic changes including CVDs [44, 45].”
BackgroundObesity-induced cognitive impairment in older adults: a microvascular perspective
Balasubramanian, P., Kiss, T., Tarantini, S., Nyúl‐Tóth, Á., Ahire, C., Yabluchanskiy, A., Csípő, T., Lipécz, Á., Tabák, Á. G., Institóris, Á., et al. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00736.2020 · Cited by 116
Are there roles for brain cell senescence in aging and neurodegenerative disorders?
Tan, F. C. C., Hutchison, E. R., Eitan, E., & Mattson, M. P. (2014) · Biogerontology · doi:10.1007/s10522-014-9532-1 · Cited by 116
“A recent study examined this question directly utilizing transgenic mice in which senescent cells (defined as those expressing p16(INK4a)) undergo apoptosis (Baker et al. 2011).”
He, Y., Li, W., Lv, D., Zhang, X., Zhang, X., Ortiz, Y. T., Budamagunta, V., Campisi, J., Zheng, G., & Zhou, D. (2020) · Aging Cell · doi:10.1111/acel.13117 · Cited by 120
“…SnCs and suppressing the SASP have emerged as attractive therapeutic strategies to extend health span (Baker et al., 2016), treat age-related diseases (Baker et al., 2011; Childs et al., 2016; Jeon et al., 2017), and ameliorate chemotherapy-induced toxicity (Demaria et al., 2017; He et al., 2019).”
BackgroundMorgan, R. G., Ives, S. J., Lesniewski, L. A., Cawthon, R. M., Andtbacka, R. H. I., Noyes, R. D., Richardson, R. S., & Donato, A. J. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00197.2013 · Cited by 115
“Consequently, senescence-associated inflammation has been implicated in aging and chronic disease (5, 24).”
BackgroundDDR-mediated crosstalk between DNA-damaged cells and their microenvironment
Malaquin, N., Carrier-Leclerc, A., Dessureault, M., & Rodier, F. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00094 · Cited by 124
“While apoptotic cells are rapidly eliminated, damaged senescent cells can persist for extended periods and accumulate in damaged or aging tissues (Baker et al., 2011).”
BackgroundPreclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic
Galiana, I., Lozano‐Torres, B., Sancho, M., Alfonso, M., Bernardos, A., Bisbal, V., Serrano, M., Martínez‐Máñez, R., & Orzáez, M. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.04.045 · Cited by 119
Han, D., Gong, H., Wei, Y., Xu, Y., Zhou, X., Wang, Z., & Feng, F. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154680 · Cited by 118
Long noncoding RNAs in aging and age-related diseases
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Biological basis and treatment of frailty and sarcopenia
Sato, R., Vatic, M., da Fonseca, G. W. P., Anker, S. D., & von Haehling, S. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae073 · Cited by 130
Yousefzadeh, M. J., Schafer, M. J., Hooten, N. N., Atkinson, E. J., Evans, M. K., Baker, D. J., Quarles, E. K., Robbins, P. D., Ladiges, W., LeBrasseur, N. K., et al. (2017) · Aging Cell · doi:10.1111/acel.12706 · Cited by 119
“Senescence-associated secretory phenotype can promote secondary senescence in healthy cells (Coppe, Desprez, Krtolica & Campisi, 2010), and senescent cells have been demonstrated to promote aging and age-related disease (Baker et al., 2011, 2016; Zhu et al., 2015).”
BackgroundSelf-citationAcceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults
Rickabaugh, T. M., Baxter, R. M., Sehl, M. E., Sinsheimer, J. S., Hultin, P. M., Hultin, L. E., Quach, A., Martı́nez-Maza, O., Horvath, S., Vilain, E. J. N., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119201 · Cited by 118
“[56] demonstrated that removal of senescent cells expressing p16 from a murine model of Progeria delayed the onset of aging-related diseases in several tissue and organ systems.”
p16-dependent increase of PD-L1 stability regulates immunosurveillance of senescent cells
Majewska, J., Agrawal, A., Mayo, A., Roitman, L., Chatterjee, R., Kralova, J. S., Landsberger, T., Katzenelenbogen, Y., Meir-Salame, T., Hagai, E., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01465-0 · Cited by 126
“Conversely, the elimination of senescent cells substantially delays the onset of age-related phenotypes, including age-associated inflammation (inflammageing), and extends the lifespan in animal models 2,3 .”
Ataxia-telangiectasia (A-T): An emerging dimension of premature ageing
Shiloh, Y., & Lederman, H. M. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.002 · Cited by 115
Senescent Cells and Their Secretory Phenotype as Targets for Cancer Therapy
Velarde, M. C., Demaria, M., & Campisi, J. (2013) · Interdisciplinary Topics in Gerontology and Geriatrics · doi:10.1159/000343572 · Cited by 112
“Finally, the recent creation of a transgenic mouse model that allows the elimination of senescent cells provides proof-of-principle that the clearance of senescent cell can ameliorate the development of certain age-associated pathologies [16].”
BackgroundInfluentialThe emerging role of senescent cells in tissue homeostasis and pathophysiology
Tominaga, K. (2015) · Pathobiology of Aging & Age-related Diseases · doi:10.3402/pba.v5.27743 · Cited by 117
“(113) have produced a transgenic mouse line in which senescent cells during the progression of agerelated disorders could be eliminated by the administration of a drug.”
BackgroundReversal of phenotypes of cellular senescence by pan-mTOR inhibition
Walters, H. E., Deneka-Hannemann, S., & Cox, L. S. (2016) · Aging · doi:10.18632/aging.100872 · Cited by 113
“Deletion of the p21 gene can prolong lifespan in telomerase-null mice [10] and clearance of p16-expressing senescent cells in vivo can rejuvenate aged mice [11].”
BackgroundGranic, A., Suetterlin, K., Shavlakadze, T., Grounds, M. D., & Sayer, A. A. (2023) · Clinical Science · doi:10.1042/cs20230319 · Cited by 124
“In animal models, the clearance of senescent cells has been shown to improve the ageing phenotype and alleviate age-related pathologies [186,187].”
BackgroundHit-and-run epigenetic editing prevents senescence entry in primary breast cells from healthy donors
Saunderson, E. A., Stepper, P., Gomm, J. J., Hoa, L., Morgan, A. A., Allen, M. D., Jones, J. L., Gribben, J. G., Jurkowski, T. P., & Ficz, G. (2017) · Nature Communications · doi:10.1038/s41467-017-01078-2 · Cited by 115
Lewińska, A., Adamczyk‐Grochala, J., Błoniarz, D., Olszowka, J., Kulpa-Greszta, M., Litwinienko, G., Tomaszewska, A., Wnuk, M., & Pązik, R. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101337 · Cited by 115
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“Cellular aging has a causal relationship with age-related phenotypes, and the reduction of senescent cells can delay tissue dysfunction and prolong health (Baker et al., 2011).”
BackgroundAge-associated callus senescent cells produce TGF-β1 that inhibits fracture healing in aged mice
Liu, J., Zhang, J., Lin, X., Boyce, B. F., Zhang, H., & Xing, L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148073 · Cited by 112
“Discussion Cellular senescence is clearly emerging as a main player in aging and age-associated diseases (43, 44).”
BackgroundAneuploidy in health, disease, and aging
Ricke, R. M., & van Deursen, J. M. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201301061 · Cited by 118
“Clearing of these p16-positive cells, genetically or pharmacologically, delays progeroid features (Baker et al., 2008, 2011), providing a crucial link between senescence and aging.”
Self-citationCellular senescence in the lung across the age spectrum
Parikh, P., Wicher, S., Khandalavala, K., Pabelick, C. M., Britt, R. D., & Prakash, Y. S. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00424.2018 · Cited by 112
“Several transgenic models using luciferase- or fluorescent-tagged promoters have been developed (12, 18, 27) to evaluate the efficacy of potential therapeutics, taking advantage of the activation of p16, p21, or p53 pathways in senescence.”
BackgroundMethodInfluentialThe Roles of MicroRNA-141 in Human Cancers: From Diagnosis to Treatment
Gao, Y., Feng, B. C., Han, S., Zhang, K., Chen, J., Li, C., Wang, R., & Chen, L. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000438641 · Cited by 114
Current Perspective in the Discovery of Anti-aging Agents from Natural Products
Ding, A., Zheng, S., Huang, X., Xing, T.-K., Wu, G.-S., Sun, H., Qi, S., & Luo, H. (2017) · Natural Products and Bioprospecting · doi:10.1007/s13659-017-0135-9 · Cited by 115
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Tissue Depletion of Taurine Accelerates Skeletal Muscle Senescence and Leads to Early Death in Mice
Ito, T., Yoshikawa, N., Inui, T., Miyazaki, N., Schaffer, S. W., & Azuma, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107409 · Cited by 113
“demonstrated that clearance of p16-positive senescent cells by a transgenic technique extends the lifespan of BubR1 progeroid mice [37].”
Azman, K. F., Safdar, A., & Zakaria, R. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111372 · Cited by 119
Telomeres, Telomerase and Ageing
Saretzki, G. C. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_9 · Cited by 120
Dagher, O., Mury, P., Thorin‐Trescases, N., Noly, P., Thorin, É., & Carrier, M. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.658400 · Cited by 119
“demonstrated that the health span in progeroid mice can be enhanced by killing SCs using a transgenic suicide gene (188).”
BackgroundSenescent Cells: A Therapeutic Target in Cardiovascular Diseases
Suda, M., Paul, K. H., Minamino, T., Miller, J. D., Lerman, A., Ellison, G. M., Tchkonia, T., & Kirkland, J. L. (2023) · Cells · doi:10.3390/cells12091296 · Cited by 119
“, INK-ATTAC mice, from which highly p16Ink4a-expressing cells can be targeted for apoptosis using an agent, AP20187, that does not target cells without high expression of p16Ink4a [207].”
BackgroundSelf-citationVerkhratsky, A., Augusto‐Oliveira, M., Pivoriūnas, A., Popov, A., Brazhe, A., & Semyanov, A. V. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02465-3 · Cited by 110
“The senescence of various cell types has been demonstrated to increase in ageing, while manipulation with cellular senescence can accelerate or retard (at least some of) age-dependent processes [7; 77; 125].”
BackgroundLadomersky, E., Zhai, L., Lauing, K. L., Bell, A., Xu, J., Kocherginsky, M., Zhang, B., Wu, J. D., Podojil, J. R., Platanias, L. C., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3874 · Cited by 110
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BackgroundInfluentialChanges in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence
Crowe, E. P., Tuzer, F., Gregory, B. D., Donahue, G., Gosai, S. J., Cohen, J., Leung, Y. Y., Yetkin, E., Nativio, R., Wang, L.-S., et al. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00208 · Cited by 110
“Frontiers in Aging Neuroscience | www.frontiersin.org 7 August 2016 | Volume 8 | Article 208”
BackgroundAdipose tissue inflammation in aging
Mau, T., & Yung, R. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.014 · Cited by 110
“Recently, studies indicate that visceral and inguinal adipose tissue in mice harbor large quantities of senescent cells that are p16 Ink4a positive 1 .”
BackgroundBarinda, A. J., Ikeda, K., Nugroho, D. B., Wardhana, D. A., Sasaki, N., Honda, S., Urata, R., Matoba, S., Hirata, K., & Emoto, N. (2020) · Nature Communications · doi:10.1038/s41467-020-14387-w · Cited by 115
Expansion and Cell-Cycle Arrest: Common Denominators of Cellular Senescence
Ogrodnik, M., Salmonowicz, H., Jurk, D., & Passos, J. F. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.06.011 · Cited by 104
LeBrasseur, N. K., Achenbach, S. J., Melton, L. J., Amin, S., & Khosla, S. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1666 · Cited by 113
“It has been reported to be a component of the senescence-associated secretory phenotype (SASP),((54)) that has been strongly supported to be a fundamental driver of agerelated tissue dysfunction.((55)) In addition to being a product of senescent cells, IGFBP-2 levels have also been reported to be inversely associated…”
BackgroundSelf-citationOxidative Stress in Mesenchymal Stem Cell Senescence: Regulation by Coding and Noncoding RNAs
Vono, R., Jover, E., Spinetti, G., & Madeddu, P. R. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7294 · Cited by 112
Yao, H., & Rahman, I. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00175.2012 · Cited by 109
Adult Stem Cells and Diseases of Aging
Boyette, L., & Tuan, R. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3010088 · Cited by 108
“Ablation of senescent cells in progeroid mice has been shown to delay or rescue the aging phenotype at the organismal level, implicating senescent cells in the pathogenesis of age-related disease in vivo [74].”
BackgroundEvidence and perspectives of cell senescence in neurodegenerative diseases
Si, Z., Sun, L., & Wang, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111327 · Cited by 105
ER stress and unfolded protein response in ocular health and disease
Kroeger, H., Chiang, W.-C. J., Felden, J., Nguyen, A., & Lin, J. H. (2018) · FEBS Journal · doi:10.1111/febs.14522 · Cited by 110
Sympathetic nervous system as a target for aging and obesity-related cardiovascular diseases
Balasubramanian, P., Hall, D., & Subramanian, M. (2018) · GeroScience · doi:10.1007/s11357-018-0048-5 · Cited by 111
Yang, S., Hwang, S., Kim, M., Seo, S. B., Lee, J., & Jeong, S. M. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0089-1 · Cited by 108
Accelerated cardiomyocyte senescence contributes to late-onset doxorubicin-induced cardiotoxicity
Mitry, M. A., Laurent, D., Keith, B. L., Sira, E., Eisenberg, C. A., Eisenberg, L. M., Joshi, S. R., Gupte, S. A., & Edwards, J. G. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00073.2019 · Cited by 109
Macrophage senescence in health and diseases
Wang, L., Hong, W., Zhu, H., He, Q., Yang, B., Wang, J., & Weng, Q. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.01.008 · Cited by 117
“Recent studies found that elimination of senescent cells can reduce chronic systemic inflammation and repair tissues 110,111 .”
BackgroundZumerle, S., Sarill, M., Saponaro, M., Colucci, M., Contu, L., Lazzarini, E., Sartori, R., Pezzini, C., Rinaldi, A. M., Scanu, A., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00663-7 · Cited by 117
Autophagy and senescence in cancer therapy
Gewirtz, D. A. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24420 · Cited by 110
Spartan deficiency causes genomic instability and progeroid phenotypes
Maskey, R. S., Kim, M. S., Baker, D. J., Childs, B. G., Malureanu, L. A., Jeganathan, K. B., Machida, Y., van Deursen, J. M., & Machida, Y. (2014) · Nature Communications · doi:10.1038/ncomms6744 · Cited by 106
Self-citationSenescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47-QPCT/L axis
Schloesser, D., Lindenthal, L., Sauer, J., Chung, K., Chavakis, T., Griesser, E., Baskaran, P., Maier-Habelsberger, U., Fundel‐Clemens, K., Schlotthauer, I., et al. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202207097 · Cited by 117
“To functionally link SHP-1 to efferocytosis suppression in these experiments we inhibited SHP using NSC-87877 in mouse and human macrophage senescent cell co-cultures.”
InfluentialDetecting and targeting senescent cells using molecularly imprinted nanoparticles
Ekpenyong‐Akiba, A. E., Canfarotta, F., Bashar Abd, H., Poblocka, M., Casulleras, M., Castilla‐Vallmanya, L., Kocsis‐Fodor, G., Kelly, M. E., Janus, J., Althubiti, M., et al. (2019) · Nanoscale Horizons · doi:10.1039/c8nh00473k · Cited by 111
Targeting senescence as an anticancer therapy
Bousset, L., & Gil, J. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13312 · Cited by 113
Role of cellular senescence in inflammation and regeneration
Saito, Y., Yamamoto, S., & Chikenji, T. (2024) · Inflammation and Regeneration · doi:10.1186/s41232-024-00342-5 · Cited by 127
“In 2011, a transgenic system called INK-ATTAC mice was used to provide additional evidence supporting the significant role of senescent cells in aging and disease [56].”
BackgroundMethodScarless wound healing: From development to senescence
Pratsinis, H., Mavrogonatou, E., & Kletsas, D. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.04.011 · Cited by 103
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.
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