The DOI matches its Crossref record, with a small difference in title or year; 211 of the 211 references it cites were found in a registry or an index.
The essence of senescence: Figure 1.
Open accessAbstract
Almost half a century after the first reports describing the limited replicative potential of primary cells in culture, there is now overwhelming evidence for the existence of “cellular senescence” in vivo. It is being recognized as a critical feature of mammalian cells to suppress tumorigenesis, acting alongside cell death programs. Here, we review the various features of cellular senescence and discuss their contribution to tumor suppression. Additionally, we highlight the power and limitations of the biomarkers currently used to identify senescent cells in vitro and in vivo.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 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 permanent growth arrest can deplete progenitor or stem cell pools, thereby compromising tissue repair and regeneration”
From Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype (2016) · cites this paper as Kuilman et al., 2010
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
“Senescent cells also communicate with their microenvironment through juxtacrine NOTCH/JAG1 signaling (Ito et al., 2017), release of ROS (Kuilman et al., 2010), cytoplasmic bridges (Video S1) (Biran et al., 2015), and extracellular vesicles, such as exosomes”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Kuilman et al., 2010
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
“Increased lysosomal β-galactosidase (GLB1) and the DNA damage repair protein p16INK4A (p16, encoded by CDKN2A) are commonly used immunohistological biomarkers of senescence [41].”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [41]
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
“senescent cells manifest dramatic alterations in their secretome, which is particularly enriched in pro-inflammatory cytokines and matrix metalloproteinases, and is referred to as the ‘senescence-associated secretory phenotype’”
From The Hallmarks of Aging (2013) · cites this paper as Kuilman et al., 2010
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“senescence can be described as a state of stable cell cycle arrest in response to diverse stresses”
From Cellular senescence and its effector programs (2014) · cites this paper as Kuilman et al. 2010
The cited source says what the claim attributes to it.
In the citing 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.”
From Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders (2011) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“Moreover, activated oncogenes can induce senescence (known as OIS) as a tumor-suppressive response, restricting the uncontrolled proliferation of potentially oncogenic cells.”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Kuilman et al., 2010
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“OIS is often mediated by the tumor suppressors p16 INK4A and ARF, both encoded by the C DKN2A locus, imposing a cell-cycle arrest (Kuilman et al., 2010; Serrano et al., 1997).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Kuilman et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“Oncogene-induced senescence (OIS) is crucial for tumour suppression.”
From A complex secretory program orchestrated by the inflammasome controls paracrine senescence (2013) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“Both normal and tumor cells undergo senescence in response to various insults that cause persistent DNA damage (Kuilman et al., 2010; Rodier and Campisi, 2011; Sikora et al., 2011; Ohtani and Hara, 2013)”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Kuilman et al., 2010
In the citing paper
“Senescent cells can communicate with the surroundings through juxtacrine NOTCH/JAG1 signaling (Hoare et al., 2016; Ito et al., 2017) or ROS secretion (Kuilman et al., 2010; Nelson et al., 2012, 2018) or cargo transfer by formation of cytoplasmic bridges (Biran et al., 2015) or release of extracellular vesicles such exosomes (Lehmann et al., 2008; Takasugi et al., 2017).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Kuilman et al., 2010
In the citing paper
“Senescence is a protective mechanism that induces cell cycle arrest to prevent transmission of defects to progeny cells, particularly to stop malignant transformation 72-74 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [74]
In the citing paper
“A persistent DNA damage response (DDR) is the most unified pathway leading to senescence, with sensing by the Ataxia Telangiectasia Mutated (ATM) protein leading to p53 phosphorylation and upregulation of cell cycle inhibitors 72-74 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [74]
In the citing paper
“These include telomere shortening and a persistent DNA damage response, autophagy and other metabolic alterations, altered protein secretion, and epigenetic gene regulation [2][3][4] .”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [3]
In the citing paper
“Cellular senescence is a state of permanent cell cycle arrest characterized by distinct metabolic activity and dramatic changes in cell morphology.1,2”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [1]
In the citing paper
“This is consistent with the hypothesis that senescence restricts tumor progression during the early stages of tumorigenesis, whereas progression to malignancy would involve evading senescence. 1”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [1]
In the citing paper
“reactive oxygen species (ROS) can mediate the deleterious effects of radiation and contribute to DNA damage and the activation of senescence pathways in cells (Diehn et al., 2009; Kuilman et al., 2010; Sonis, 2009; Spitz et al., 2004).”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Kuilman et al., 2010
In the citing paper
“The activation of the DNA damage response is one of the main mediators of cell senescence, which results in irreversible growth arrest (Kuilman et al., 2010; Rodier and Campisi, 2011).”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Kuilman et al., 2010
In the citing paper
“The activation of the RB tumor suppressive pathway by the accumulation of p16 is often considered a key mechanism triggering cell senescence in several systems, including skin keratinocytes (Kuilman et al., 2010; Luis et al., 2011).”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Kuilman et al., 2010
In the citing paper
“Senescence can be triggered by multiple mechanisms, including those resulting in ROS production and oxidative stress (Kuilman et al., 2010; Rodier and Campisi, 2011).”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Kuilman et al., 2010
In the citing paper
“Indeed, gene expression analysis with NanoString of cases without apparent DNA damage as shown by γH2AX revealed up-regulation of pathways involved in cellular senescence [82]”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [82]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Items 201–211 of 211
Role for IGFBP7 in Senescence Induction by BRAF
Wajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M., & Green, M. R. (2010) · Cell · doi:10.1016/j.cell.2010.05.014 · Cited by 52
Lü, C., Sheehan, C., Rak, J. W., Chambers, C. A., Hozumi, N., & Kerbel, R. S. (1996) · PubMed · Cited by 49
Yuan, H., Kaneko, T., & Matsuo, M. (1995) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(95)01584-m · Cited by 34
Oct‐1 is involved in the transcriptional repression of the p15INK4b gene
Hitomi, T., Matsuzaki, Y., Yasuda, S., Kawanaka, M., Yogosawa, S., Koyama, M., Tantin, D. R., & Sakai, T. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.092 · Cited by 23
BS69 is involved in cellular senescence through the p53–p21Cip1 pathway
Zhang, W., Chan, H. M., Gao, Y., Poon, R. Y. C., & Wu, Z. (2007) · EMBO Reports · doi:10.1038/sj.embor.7401049 · Cited by 20
Senescence: a companion in chemotherapy?
Berns, A. J. M. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00063-6 · Cited by 16
Gene expression analysis of urethane-induced lung tumors in rasH2 mice
Okamura, M., Unami, A., Matsumoto, M., Oishi, Y., Kashida, Y., & Mitsumori, K. (2005) · Toxicology · doi:10.1016/j.tox.2005.09.021 · Cited by 11
Lack of Correlation between IGFBP7 Expression and BRAF Mutational Status in Melanoma
Schrama, D., Kneitz, H., Willmes, C., Adam, C., Houben, R., & Becker, J. C. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.304 · Cited by 10
Ras and pRb: The Relationship Gets Yet More Intimate
Peeper, D. S. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.007 · Cited by 3
Self-citationAccumulation of aberrant Y chromosomes in ?-ray-induced thymic lymphomas lacking p53
Chou, D., Matsuki, J., Saitou, Y., Kosugi, S., Shinbo, T., Gejyo, F., Niwa, O., & Kominami, R. (1999) · Molecular Carcinogenesis · doi:10.1002/(sici)1098-2744(199911)26:3 · Cited by 1
Telomerase activity in human germline and embryonic tissues and cells
Wright, W. E., Piatyszek, M. A., Rainey, W. E., Byrd, W., & Shay, J. W. (1996) · Developmental Genetics · doi:10.1002/(sici)1520-6408(1996)18:2
Flagged first, then by citations
Research works printed but not linked: 2
- 10.1016/j.cell.2008.06.049 · DOI · Paper page
- 10.1016/S0092-8674(03)00550-6 · DOI · Paper page
Cited by
Sorted by citations
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Cellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225
Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
Metadata
- Authors
- Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-11-15
- Volume
- 24
- Issue
- 22
- Pages
- 2463-2479
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2975923
- OpenAlex
- W2116437342
- Cited by
- 2,038
- References
- 211
- Citations by year
- 2026: 53 · 2025: 97 · 2024: 111 · 2023: 133 · 2022: 134 · 2021: 171 · 2020: 161 · 2019: 147 · 2018: 128 · 2017: 138 · 2016: 168 · 2015: 153 · 2014: 179 · 2013: 134 · 2012: 79
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- KWF Kankerbestrijding
- 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 › Oncology › Cancer-related Molecular Pathways
- Keywords
- cellular senescence, replicative senescence, tumor suppression, senescence biomarkers, primary cell culture
- MeSH terms
- Animals, Cells, Humans, Neoplasms, Biomarkers, Cellular Senescence
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
