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.
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“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]
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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]
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“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); senescence is characterized by the inability to proliferate despite sufficient nutrients and…”
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Cell fusion induced by ERVWE1 or measles virus causes cellular senescence
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Discovery of piperlongumine as a potential novel lead for the development of senolytic agents
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Identification of senescent cell surface targetable protein DPP4
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Vascular Cell Senescence Contributes to Blood–Brain Barrier Breakdown
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“Senescent cells display profound changes in nuclear and chromatin organization, gene expression, and cell metabolism (Kuilman et al., 2010).”
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Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce
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Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis
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Aging and reprogramming: a two-way street
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Oncogene-induced senescence results in marked metabolic and bioenergetic alterations
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The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype
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Senescent cells communicate via intercellular protein transfer
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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
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