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
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218 · cited 15×
“This is also exemplified by the signaling routes relaying OIS by RAS versus BRAF: Whereas RAS-induced senescence can be bypassed by abrogation of the p16–RB pathway (Serrano et al. 1997), BRAF-triggered senescence cannot be bypassed by functional inactivation of p16, be it alone (Michaloglou Kuilman et al.”
BackgroundInfluentialExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Massagué, J. (2008) · Cell · doi:10.1016/j.cell.2008.07.001 · Cited by 3,907
RAS Is Regulated by the let-7 MicroRNA Family
Johnson, S., Großhans, H., Shingara, J., Byrom, M., JARVIS, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., & Slack, F. J. (2005) · Cell · doi:10.1016/j.cell.2005.01.014 · Cited by 3,699
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,917 · cited 1×
“Moreover, the DNA damage kinases ATM and ATR are activated in senescent cells (D’Adda di Fagagna et al. 2003).”
BackgroundTumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes
Land, H., Parada, L. F., & Weinberg, R. A. (1983) · Nature · doi:10.1038/304596a0 · Cited by 2,804
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
A survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,379 · cited 4×
“This notwithstanding, the observations are in agreement with the proposed deleterious effects of senescent cells on their microenvironment, possibly contributing to age-related disease (Campisi 2005).”
BackgroundResultInfluentialRb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 7×
“They include the loss of proliferation, morphological changes, increased SAb-GAL activity, the production of SAHF, and a rise in 2468 GENES & DEVELOPMENT the levels of DDR markers as well as the cell cycle inhibitors p16INK4A, p15INK4B, p21CIP1, and p53.”
BackgroundInfluentialPersistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160
Self-citationOncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
Kuilman, T., Michaloglou, C., Vredeveld, L. C. W., Douma, S., van Doorn, R., Desmet, C. J., Aarden, L. A., Mooi, W. J., & Peeper, D. S. (2008) · Cell · doi:10.1016/j.cell.2008.03.039 · Cited by 2,086 · cited 13×
“…interference with expression of other genes—including those encoding p53, C/EBPb, or 2466 GENES & DEVELOPMENT interleukin-6 (IL-6) (see below)—also reduces SAHF-positivity, which is associated with abrogation of senescence (Chan et al. 2005; Ye et al. 2007; Zhang et al. 2007; Kuilman et al. 2008).”
BackgroundInfluentialSelf-citationSenescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986
Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
Di Micco, R., Fumagalli, M., Cicalese, A., Piccinin, S., Gasparini, P., Luise, C., Schurra, C., Garre’, M., Giovanni Nuciforo, P., Bensimon, A., et al. (2006) · Nature · doi:10.1038/nature05327 · Cited by 1,821
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820 · cited 6×
“To explore the viability of such an approach, the Jacks (Ventura et al. 2007) and Lowe (Xue et al. 2007) laboratories have employed conditional mouse models.”
BackgroundMethodInfluentialChemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801 · cited 11×
“Moreover, expression of several senescence-associated genes is reduced when tumors progress beyond the senescent stage (Chen et al. 2005; Collado et al. 2005; Lazzerini Denchi et al. 2005; Acosta et al. 2008).”
BackgroundInfluentialHigh frequency of BRAF mutations in nevi
Pollock, P. M., Harper, U. L., Hansen, K. S., Yudt, L. M., Stark, M., Robbins, C. M., Moses, T. Y., Hostetter, G., Wagner, U., Kakareka, J., et al. (2003) · Nature Genetics · doi:10.1038/ng1054 · Cited by 1,730
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730
Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J., & Toussaint, O. (2009) · Nature Protocols · doi:10.1038/nprot.2009.191 · Cited by 1,668
WATSON, J. D. (1972) · Nature New Biology · doi:10.1038/newbio239197a0 · Cited by 1,632
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19
Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., & Sherr, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80452-3 · Cited by 1,566
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457
Senescence-associated β-galactosidase is lysosomal β-galactosidase.
Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00199.x · Cited by 1,444
Lowe, S. W., Cepero, E., & Evan, G. I. (2004) · Nature · doi:10.1038/nature03098 · Cited by 1,374
Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., & Yamanaka, S. (2009) · Nature · doi:10.1038/nature08235 · Cited by 1,301
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220
Di Leonardo, A., Linke, S. P., Clarkin, K., & Wahl, G. M. (1994) · Genes & Development · doi:10.1101/gad.8.21.2540 · Cited by 1,215
Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., & Klingelhutz, A. J. (1998) · Nature · doi:10.1038/23962 · Cited by 1,206 · cited 2×
“Disruption of the p16–RB pathway collaborates with ectopic hTERT expression in the immortalization of both primary human epithelial cells (Kiyono et al. 1998) and melanocytes (Gray-Schopfer et al.”
BackgroundBrafV600E cooperates with Pten loss to induce metastatic melanoma
Dankort, D., Curley, D. P., Cartlidge, R. A., Nelson, B., Karnezis, A. N., Damsky Jr, W. E., You, M. J., DePinho, R. A., McMahon, M., & Bosenberg, M. (2009) · Nature Genetics · doi:10.1038/ng.356 · Cited by 1,189
Living on a break: cellular senescence as a DNA-damage response
d'Adda di Fagagna, F. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2440 · Cited by 1,170
Senescence in tumours: evidence from mice and humans
Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124 · cited 1×
“DEC1, DCR2 (Collado et al. 2005), and PAI1 (Goldstein et al. 1994) have also been used as senescence biomarkers (Collado and Serrano 2010).”
Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003) · Nature Cell Biology · doi:10.1038/ncb1024 · Cited by 1,116
Linking the p53 tumour suppressor pathway to somatic cell reprogramming
Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M., & Belmonte, J. C. I. (2009) · Nature · doi:10.1038/nature08311 · Cited by 1,115
Cellular Senescence in Aging Primates
Herbig, U., Ferreira, M., Condel, L., Carey, D., & Sedivy, J. M. (2006) · Science · doi:10.1126/science.1122446 · Cited by 1,101
Autophagy mediates the mitotic senescence transition
Young, A. R. J., Narita, M., Ferreira, M., Kirschner, K., Sadaie, M., Darot, J. F. J., Tavaré, S., Arakawa, S., Shimizu, S., Watt, F. M., et al. (2009) · Genes & Development · doi:10.1101/gad.519709 · Cited by 1,078
Endothelial Cell Senescence in Human Atherosclerosis: Role of Telomere in Endothelial Dysfunction
Minamino, T., Miyauchi, H., Yoshida, T., Ishida, Y., Yoshida, H., & Komuro, I. (2002) · Circulation · doi:10.1161/01.cir.0000013836.85741.17 · Cited by 1,061
A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer Therapy
Schmitt, C. A., Fridman, J. S., Yang, M., Lee, S., Baranov, E., Hoffman, R. M., & Lowe, S. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00734-1 · Cited by 1,050
The signals and pathways activating cellular senescence
Ben-Porath, I., & Weinberg, R. A. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.10.013 · Cited by 1,046
A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
Marión, R. M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M., & Blasco, M. A. (2009) · Nature · doi:10.1038/nature08287 · Cited by 1,028 · cited 2×
“…and p53 limit the efficiency of iPS cell formation, it has been suggested that cellular senescence counteracts the induced conversion of primary cells into pluripotent stem cells (Banito et al. 2009; Hong et al. 2009; Kawamura et al. 2009; Li et al. 2009; Marión et al. 2009; Utikal et al. 2009).”
BackgroundFeedback between p21 and reactive oxygen production is necessary for cell senescence
Passos, J. F., Nelson, G., Wang, C., Richter, T., Simillion, C., Proctor, C. J., Miwa, S., Olijslagers, S., Hallinan, J., Wipat, A., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.5 · Cited by 1,019 · cited 2×
“A recent systems biology study has suggested that ROS mediates senescence through induction of DNA damage foci, with a contribution of p21CIP1 (Passos et al. 2010).”
BackgroundAlcorta, D. A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., & Barrett, J. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13742 · Cited by 1,008 · cited 2×
“…and p15INK4B, also often accumulate in senescent cells, and have been used as markers reflecting the activation of these pathways in senescence (Alcorta et al. 1996; Hara et al. 1996; Reznikoff et al. 1996; Serrano et al. 1997; Erickson et al. 1998; Lin et al. 1998; Robles and Adami 1998; Zhu…”
BackgroundVaziri, H., & Benchimol, S. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70109-5 · Cited by 1,003
Chin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979 · cited 1×
“In the absence of p53, however, telomere dysfunction instead promotes tumorigenesis (Chin et al. 1999).”
BackgroundThe Ink4/Arf locus is a barrier for iPS cell reprogramming
Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Cañamero, M., Blasco, M. A., & Serrano, M. (2009) · Nature · doi:10.1038/nature08290 · Cited by 968
Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.19.3008 · Cited by 945
Direct cell reprogramming is a stochastic process amenable to acceleration
Hanna, J., Saha, K., Pando, B., van Zon, J., Lengner, C. J., Creyghton, M. P., van Oudenaarden, A., & Jaenisch, R. (2009) · Nature · doi:10.1038/nature08592 · Cited by 938
Senescence-messaging secretome: SMS-ing cellular stress
Kuilman, T., & Peeper, D. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2560 · Cited by 909
Self-citationWajapeyee, N., Serra, R. W., Zhu, X., Mahalingam, M., & Green, M. R. (2008) · Cell · doi:10.1016/j.cell.2007.12.032 · Cited by 903
Kurz, D. J., Decary, S., Hong, Y., & Erusalimsky, J. D. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.20.3613 · Cited by 899
Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
Elenbaas, B., Spirio, L., Koerner, F., Fleming, M. D., Zimonjic, D. B., Donaher, J. L., Popescu, N. C., Hahn, W. C., & Weinberg, R. A. (2001) · Genes & Development · doi:10.1101/gad.828901 · Cited by 878
Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis
Quintanilla, M., Brown, K., Ramsden, M., & Balmain, A. (1986) · Nature · doi:10.1038/322078a0 · Cited by 852
Immortalization eliminates a roadblock during cellular reprogramming into iPS cells
Utikal, J. S., Polo, J. M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R. M., Khalil, A., Rheinwald, J. G., & Hochedlinger, K. (2009) · Nature · doi:10.1038/nature08285 · Cited by 851
Bracken, A. P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard-Mönch, K., Minucci, S., Porse, B. T., Marine, J.-C., et al. (2007) · Genes & Development · doi:10.1101/gad.415507 · Cited by 850
Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis
Sharpless, N. E., Bardeesy, N., Lee, K.-H., Carrasco, D., Castrillon, D. H., Aguirre, A. J., Wu, E. A., Horner, J. W., & DePinho, R. A. (2001) · Nature · doi:10.1038/35092592 · Cited by 848
Senescence of human fibroblasts induced by oncogenic Raf
Zhu, J., Woods, D., McMahon, M., & Bishop, J. M. (1998) · Genes & Development · doi:10.1101/gad.12.19.2997 · Cited by 826
Telomeres and telomerase in cancer
Artandi, S. E., & DePinho, R. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp268 · Cited by 823
Tuveson, D. A., Shaw, A. T., Willis, N. A., Silver, D. P., Jackson, E. L., Chang, S., Mercer, K. L., Grochow, R., Hock, H., Crowley, D., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00085-6 · Cited by 798
Microarray analysis of replicative senescence
Shelton, D. N., Chang, E., Whittier, P. S., Choi, D., & Funk, W. D. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80420-5 · Cited by 764
A role for both RB and p53 in the regulation of human cellular senescence*1
SHAY, J. (1991) · Experimental Cell Research · doi:10.1016/0014-4827(91)90453-2 · Cited by 757
Senescence and immortalization: role of telomeres and telomerase
Shay, J. W., & Wright, W. E. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh296 · Cited by 747
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745
Telomerase maintains telomere structure in normal human cells
Kenichi, M., Yu, E. Y., Shilagardi, K., Ben‐Porath, I., Currier, J. L., Metz, G. B., Brooks, M. W., Kaneko, S., Seishi, M., DeCaprio, J. A., et al. (2006) · Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) · Cited by 738
Regulation of p16 CDKN2 Expression and Its Implications for Cell Immortalization and Senescence
Hara, E., Smith, R., Parry, D., Tahara, H., Stone, S., & Peters, G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.859 · Cited by 733
Oxidative DNA damage and senescence of human diploid fibroblast cells.
Chen, Q., Fischer, A., Reagan, J. D., Yan, L. J., & Ames, B. N. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4337 · Cited by 720
Zhang, R., Poustovoitov, M. V., Ye, X., Santos, H. A., Chen, W., Daganzo, S. M., Erzberger, J. P., Serebriiskii, I. G., Canutescu, A. A., Dunbrack, R. L., et al. (2005) · Developmental Cell · doi:10.1016/j.devcel.2004.10.019 · Cited by 699
Developmental and tissue-specific regulation of mouse telomerase and telomere length.
Prowse, K. R., & Greider, C. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4818 · Cited by 697
Ras Proteins Induce Senescence by Altering the Intracellular Levels of Reactive Oxygen Species
Lee, A. C., Fenster, B. E., Ito, H., Takeda, K., Bae, N. S., Hirai, T., Yu, Z.-X., Ferrans, V. J., Howard, B. H., & Finkel, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.7936 · Cited by 691
Patton, E. E., Widlund, H. R., Kutok, J. L., Kopani, K. R., Amatruda, J. F., Murphey, R. D., Berghmans, S., Mayhall, E. A., Traver, D. J., Fletcher, C. D. �., et al. (2005) · Current Biology · doi:10.1016/j.cub.2005.01.031 · Cited by 684
Age-related decline in chaperone-mediated autophagy
Cuervo, A. M., & Dice, J. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002102200 · Cited by 665
Senescence impairs successful reprogramming to pluripotent stem cells
Banito, A., Rashid, S. T., Acosta, J. C., Li, S., Pereira, C. F., Geti, I., Pinho, S., Silva, J. C., Azuara, V., Walsh, M., et al. (2009) · Genes & Development · doi:10.1101/gad.1811609 · Cited by 642
Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells.
Chen, Q., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4130 · Cited by 641
(2002) · PubMed · Cited by 640
Woods, D. B., Parry, D., Cherwinski, H. M., Bosch, E., Lees, E. M., & McMahon, M. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5598 · Cited by 639
Kortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637 · cited 1×
“Likewise, the ECM regulator PAI-1 has been shown to mediate senescence (Kortlever et al. 2006), although clinical data seem to point to a more complex picture (Kuilman and Peeper 2009).”
BackgroundParrinello, S., Coppe, J.-P., Krtolica, A., & Campisi, J. (2005) · Journal of Cell Science · doi:10.1242/jcs.01635 · Cited by 631
A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation
Narita, M., Narita, M., Krizhanovsky, V., Nuñez, S., Chicas, A., Hearn, S. A., Myers, M. P., & Lowe, S. W. (2006) · Cell · doi:10.1016/j.cell.2006.05.052 · Cited by 629
Oncogenic Braf Induces Melanocyte Senescence and Melanoma in Mice
Dhomen, N. S., Reis-Filho, J. S., Dias, S. D. R., Hayward, R., Savage, K., Delmas, V., Larue, L., Pritchard, C. A., & Marais, R. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.02.022 · Cited by 626
Hypervariable ultra-long telomeres in mice
Kipling, D., & Cooke, H. J. (1990) · Nature · doi:10.1038/347400a0 · Cited by 614
(2003) · PubMed · Cited by 608
Targeted disruption of the three Rb-related genes leads to loss of G 1 control and immortalization
Sage, J., Mulligan, G. J., Attardi, L. D., Miller, A., Chen, S., Williams, B., Theodorou, E., & Jacks, T. (2000) · Genes & Development · doi:10.1101/gad.843200 · Cited by 582
Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context
Guerra, C. E., Mijimolle, N., Dhawahir, A., Dubus, P. R., Barradas, M., Serrano, M., Campuzano, V., & Barbacid, M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00191-0 · Cited by 577
Accumulation of senescent cells in Mitotic tissue of aging primates
Jeyapalan, J. C., Ferreira, M., Sedivy, J. M., & Herbig, U. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.008 · Cited by 571
Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice
Krimpenfort, P., Quon, K. C., Mooi, W. J., Loonstra, A., & Berns, A. (2001) · Nature · doi:10.1038/35092584 · Cited by 568 · cited 2×
“Genetic disruption of the gene encoding p16INK4A predisposes mice and humans to tumorigenesis, includ- ing melanoma (Gruis et al. 1995; Krimpenfort et al. 2001; Sharpless et al. 2001).”
BackgroundSelf-citation[Principle of marginotomy in template synthesis of polynucleotides].
Olovnikov, A. M. (1971) · PubMed · Cited by 567
YUDKIN, J. (1972) · Nature · doi:10.1038/239197a0 · Cited by 545
Takahashi, A., Ohtani, N., Yamakoshi, K., Iida, S.-I., Tahara, H., Nakayama, K., Nakayama, K. I., Ide, T., Saya, H., & Hara, E. (2006) · Nature Cell Biology · doi:10.1038/ncb1491 · Cited by 528
A negative feedback signaling network underlies oncogene-induced senescence
Courtois-Cox, S., Genther Williams, S. M., Reczek, E. E., Johnson, B. W., McGillicuddy, L. T., Johannessen, C. M., Hollstein, P. E., MacCollin, M., & Cichowski, K. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.003 · Cited by 501
Robles, S. J., & Adami, G. R. (1998) · Oncogene · doi:10.1038/sj.onc.1201862 · Cited by 498
Tanaka, N., Ishihara, M., Kitagawa, M., Harada, H., Kimura, T., Matsuyama, T., Lamphier, M. S., Aizawa, S., Mak, T. W., & Taniguchi, T. (1994) · Cell · doi:10.1016/0092-8674(94)90132-5 · Cited by 491
Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis
Sarkisian, C. J., Keister, B. A., Stairs, D. B., Boxer, R. B., Moody, S. E., & Chodosh, L. A. (2007) · Nature Cell Biology · doi:10.1038/ncb1567 · Cited by 490
Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions
Ramirez, R. D., Morales, C. P., Herbert, B.-S., Rohde, J. M., Passons, C., Shay, J. W., & Wright, W. E. (2001) · Genes & Development · doi:10.1101/gad.859201 · Cited by 444 · cited 4×
“1995), while the replicative potential of human melanocytes and epithelial cells depends largely on the composition of the culture medium used, as well as on the use of feeder layers (Ramirez et al. 2001; Bennett and Medrano 2002; Bennett 2003).”
BackgroundInfluentialChen, Q. M., Bartholomew, J. C., Campisi, J., Acosta, M., REAGAN, J. D., & Ames, B. N. (1998) · Biochemical Journal · doi:10.1042/bj3320043 · Cited by 442
Telomerase therapeutics for cancer: challenges and new directions
Shay, J. W., & Wright, W. E. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2081 · Cited by 442
Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1
Itahana, K., Zou, Y., Itahana, Y., Martinez, J.-L., Beausejour, C., Jacobs, J. J. L., van Lohuizen, M., Band, V., Campisi, J., & Dimri, G. P. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.389-401.2003 · Cited by 438
Agger, K., Cloos, P. A. C., Rudkjær, L., Williams, K., Andersen, G., Christensen, J., & Helin, K. (2009) · Genes & Development · doi:10.1101/gad.510809 · Cited by 427
Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation
Wu, C.-H., van Riggelen, J., Yetil, A., Fan, A. C., Bachireddy, P., & Felsher, D. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701953104 · Cited by 417
Puyol, M., Martín, A., Dubus, P., Mulero, F., Pizcueta, P., Khan, G., Guerra, C., Santamaría, D., & Barbacid, M. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.05.025 · Cited by 415
Dannenberg, J.-H., van Rossum, A., Schuijff, L., & te Riele, H. (2000) · Genes & Development · doi:10.1101/gad.847700 · Cited by 413
Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence
Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408 · cited 1×
“It is widely assumed that not oxygen itself, but rather ROS produced by mitochondria are involved in senescence (Lu and Finkel 2008; Moiseeva et al. 2009).”
BackgroundMitogen‐activated protein kinase p38 defines the common senescence‐signalling pathway
Iwasa, H., Han, J., & Ishikawa, F. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00620.x · Cited by 407
The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence
Mallette, F. A., Gaumont-Leclerc, M.-F., & Ferbeyre, G. (2007) · Genes & Development · doi:10.1101/gad.1487307 · Cited by 406
Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence
Lin, H.-K., Chen, Z., Wang, G., Nardella, C., Lee, S.-W., Chan, C.-H., Yang, W.-L., Wang, J., Egia, A., Nakayama, K. I., et al. (2010) · Nature · doi:10.1038/nature08815 · Cited by 400
Cellular senescence in naevi and immortalisation in melanoma: a role for p16?
Gray-Schopfer, V. C., Cheong, S. C., Chong, H., Chow, J., Moss, T., Abdel-Malek, Z. A., Marais, R., Wynford-Thomas, D., & Bennett, D. C. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603283 · Cited by 394
Low oxygen concentration extends the lifespan of cultured human diploid cells
Packer, L., & FUEHR, K. (1977) · Nature · doi:10.1038/267423a0 · Cited by 393
Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence
Chicas, A., Wang, X., Zhang, C., McCurrach, M., Zhao, Z., Mert, O., Dickins, R. A., Narita, M., Zhang, M., & Lowe, S. W. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.023 · Cited by 388
Chang, B.-D., Xuan, Y., Broude, E. V., Zhu, H., Schott, B., Fang, J., & Roninson, I. B. (1999) · Oncogene · doi:10.1038/sj.onc.1203078 · Cited by 387
The role of chondrocyte senescence in osteoarthritis
Price, J. S., Waters, J. G., Darrah, C., Pennington, C., Edwards, D. R., Donell, S. T., & Clark, I. M. (2002) · Aging Cell · doi:10.1046/j.1474-9728.2002.00008.x · Cited by 386
Vaziri, H., West, M. D., Allsopp, R., Davison, T. S., Wu, Y., Arrowsmith, C. H., Poirier, G. G., & Benchimol, S. (1997) · The EMBO Journal · doi:10.1093/emboj/16.19.6018 · Cited by 384
Wang, W., Chen, J. X., Liao, R., Deng, Q., Zhou, J. J., Huang, S., & Sun, P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.10.3389-3403.2002 · Cited by 376
Alimonti, A., Nardella, C., Chen, Z., Clohessy, J. G., Carracedo, A., Trotman, L. C., Cheng, K., Varmeh, S., Kozma, S. C., Thomas, G., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40535 · Cited by 374
Is β-Galactosidase Staining a Marker of Senescence in Vitro and in Vivo?
Severino, J., Allen, R. G., Balin, S., Balin, A., & Cristofalo, V. J. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4875 · Cited by 370
Failure to Phosphorylate the Retinoblastoma Gene Product in Senescent Human Fibroblasts
Stein, G. H., Beeson, M., & Gordon, L. (1990) · Science · doi:10.1126/science.2166342 · Cited by 370
Short Dysfunctional Telomeres Impair Tumorigenesis in the INK4aΔ2/3 Cancer-Prone Mouse
Greenberg, R. A., Chin, L., Femino, A., Lee, K.-H., Gottlieb, G. J., Singer, R. H., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80761-8 · Cited by 367 · cited 1×
“This is consistent with a significant drop in the tumor take of telomerasedeficient (mTR / ) mice in the context of INK4a/Arf loss (Greenberg et al. 1999).”
Historical claims and current interpretations of replicative aging
Wright, W. E., & Shay, J. W. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-682 · Cited by 355
Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS
Barradas, M., Anderton, E., Acosta, J. C., Li, S., Banito, A., Rodriguez-Niedenführ, M., Maertens, G., Banck, M., Zhou, M.-M., Walsh, M. J., et al. (2009) · Genes & Development · doi:10.1101/gad.511109 · Cited by 352
Denoyelle, C., Abou-Rjaily, G., Bezrookove, V., Verhaegen, M., Johnson, T. M., Fullen, D. R., Pointer, J. N., Gruber, S. B., Su, L. D., Nikiforov, M. A., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1471 · Cited by 349
Polycomb CBX7 has a unifying role in cellular lifespan.
Gil, J., Bernard, D., Martínez, D., & Beach, D. (2004) · Nature Cell Biology · doi:10.1038/ncb1077 · Cited by 341
Yang, G., Rosen, D. G., Zhang, Z., Bast, R. C., Mills, G. B., Colacino, J. A., Mercado-Uribe, I., & Liu, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605752103 · Cited by 341
p53 isoforms Δ133p53 and p53β are endogenous regulators of replicative cellular senescence
Fujita, K., Mondal, A. M., Horikawa, I., Nguyen, G. H., Kumamoto, K., Sohn, J. J., Bowman, E. D., Mathe, E. A., Schetter, A. J., Pine, S. R., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1928 · Cited by 336
Lu, T., & Finkel, T. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.011 · Cited by 327
Healing and Hurting: Molecular Mechanisms, Functions, and Pathologies of Cellular Senescence
Adams, P. D. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.021 · Cited by 326
PRAK Is Essential for ras-Induced Senescence and Tumor Suppression
Sun, P., Yoshizuka, N., New, L., Moser, B. A., Li, Y., Liao, R., Xie, C., Chen, J., Deng, Q., Yamout, M., et al. (2007) · Cell · doi:10.1016/j.cell.2006.11.050 · Cited by 321
Short Telomeres Limit Tumor Progression In Vivo by Inducing Senescence
Feldser, D. M., & Greider, C. W. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.026 · Cited by 314
Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds
Gruis, N. A., van der Velden, P. A., Sandkuijl, L. A., Prins, D. E. M., Weaver-Feldhaus, J., Kamb, A., Bergman, W., & Frants, R. R. (1995) · Nature Genetics · doi:10.1038/ng0795-351 · Cited by 312
Increased activity of p53 in senescing fibroblasts
Atadja, P., Wong, H., Garkavtsev, I., Veillette, C., & Riabowol, K. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8348 · Cited by 308
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · cited 5×
“Subsequent work from various laboratories has revealed that cells undergoing either replicative or premature senescence display profound changes in their secretome, termed the senescence-associated secretory phenotype (SASP) (Coppé et al. 2008; Rodier et al. 2009).”
BackgroundInfluentialReplicative senescence: a critical review
Cristofalo, V. J., Lorenzini, A., Allen, R. G., Torres, C. A., & Tresini, M. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.07.010 · Cited by 285
BRAFE600 in benign and malignant human tumours
Michaloglou, C., Vredeveld, L. C. W., Mooi, W. J., & Peeper, D. S. (2007) · Oncogene · doi:10.1038/sj.onc.1210704 · Cited by 278
Self-citationThe promises and perils of p53
Krizhanovsky, V., & Lowe, S. W. (2009) · Nature · doi:10.1038/4601085a · Cited by 274
Reversal of Senescence in Mouse Fibroblasts through Lentiviral Suppression of p53
Dirac, A. M. G., & Bernards, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300023200 · Cited by 265
Cdk2 suppresses cellular senescence induced by the c-myc oncogene
Campaner, S., Doni, M., Hydbring, P., Verrecchia, A., Bianchi, L., Sardella, D., Schleker, T., Perna, D., Tronnersjö, S., Murga, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb2004 · Cited by 258
DNA Damage Signaling and p53-dependent Senescence after Prolonged β-Interferon Stimulation
Moiseeva, O., Mallette, F. A., Mukhopadhyay, U. K., Moores, A., & Ferbeyre, G. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-09-0858 · Cited by 252
YANG, N., & HU, M. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.07.011 · Cited by 245
Furumoto, K., Inoue, E., Nagao, N., Hiyama, E., & Miwa, N. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00351-8 · Cited by 240
VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400
Young, A. P., Schlisio, S., Minamishima, Y. A., Zhang, Q., Li, L., Grisanzio, C., Signoretti, S., & Kaelin, W. G. (2008) · Nature Cell Biology · doi:10.1038/ncb1699 · Cited by 239
Ye, X., Zerlanko, B. J., Kennedy, A. L., Gowrishankar, B., Zhang, R., & Adams, P. D. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.034 · Cited by 237
Lack of Replicative Senescence in Cultured Rat Oligodendrocyte Precursor Cells
Tang, D. G., Tokumoto, Y. M., Apperly, J. A., Lloyd, A. C., & RAFF, M. C. (2001) · Science · doi:10.1126/science.1056780 · Cited by 227
The first molecular details of ALT in human tumor cells
Muntoni, A., & Reddel, R. R. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi266 · Cited by 226
Human melanocyte senescence and melanoma susceptibility genes
Bennett, D. C. (2003) · Oncogene · doi:10.1038/sj.onc.1206446 · Cited by 220
Extended Culture of Mouse Embryo Cells Without Senescence: Inhibition by Serum
Loo, D. T., Fuquay, J. I., Rawson, C. L., & Barnes, D. W. (1987) · Science · doi:10.1126/science.3494308 · Cited by 219
Role of p14ARF in Replicative and Induced Senescence of Human Fibroblasts
Wei, W., Hemmer, R. M., & Sedivy, J. M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.20.6748-6757.2001 · Cited by 217
Cosme‐Blanco, W., Shen, M., Lazar, A. J. F., Pathak, S., Lozano, G., Multani, A. S., & Chang, S. (2007) · The EMBO Reports · doi:10.1038/sj.embor.7400937 · Cited by 205
Denchi, E. L., Attwooll, C., Pasini, D., & Helin, K. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.7.2660-2672.2005 · Cited by 195
Deng, Q., Liao, R., Wu, B., & Sun, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308644200 · Cited by 188
Uncoupling the Senescent Phenotype from Telomere Shortening in Hydrogen Peroxide-Treated Fibroblasts
Chen, Q. M., Prowse, K. R., Tu, V. C., Purdom, S., & Linskens, M. H. K. (2001) · Experimental Cell Research · doi:10.1006/excr.2001.5182 · Cited by 186 · cited 1×
“A flat cell phenotype is commonly seen in cells undergoing H-RASV12induced senescence (Serrano et al. 1997; Denoyelle et al. 2006), stress-induced senescence (Parrinello et al. 2003), or DNA damage-induced senescence (Chen and Ames 1994; Chen et al. 2001).”
BackgroundBennecke, M., Kriegl, L., Bajbouj, M., Retzlaff, K., Robine, S., Jung, A., Arkan, M. C., Kirchner, T., & Greten, F. R. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.06.013 · Cited by 186
Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184
Lack of Replicative Senescence in Normal Rodent Glia
Mathon, N. F., Malcolm, D. S., Harrisingh, M. C., Cheng, L., & Lloyd, A. C. (2001) · Science · doi:10.1126/science.1056782 · Cited by 183
Adams, P. D. (2007) · Gene · doi:10.1016/j.gene.2007.04.020 · Cited by 182
(1996) · PubMed · Cited by 180
Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice
Goel, V., Ibrahim, N., Jiang, G., Singhal, M., Fee, S., Flotte, T. J., Westmoreland, S. V., Haluska, F. S., Hinds, P. W., & Haluska, F. G. (2009) · Oncogene · doi:10.1038/onc.2009.95 · Cited by 176
Real-time in vivo imaging of p16Ink4a reveals cross talk with p53
Yamakoshi, K., Takahashi, A., Hirota, F., Nakayama, R., Ishimaru, N., Kubo, Y., Mann, D. J., Ohmura, M., Hirao, A., Saya, H., et al. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200904105 · Cited by 172
Lü, C., Vickers, M. F., & Kerbel, R. S. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9215 · Cited by 170
Wei, S., Wei, S., & Sedivy, J. M. (1999) · PubMed · Cited by 166
Franza, B. R., Maruyama, K., Garrels, J. I., & Ruley, H. E. (1986) · Cell · doi:10.1016/0092-8674(86)90462-9 · Cited by 166
Bulavin, D. V., Kovalsky, O., Hollander, M. C., & Fornace, A. J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.11.3859-3871.2003 · Cited by 161
Arf tumor suppressor promoter monitors latent oncogenic signals in vivo
Zindy, F., Williams, R. T., Baudino, T. A., Rehg, J. E., Skapek, S. X., Cleveland, J. L., Roussel, M. F., & Sherr, C. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536808100 · Cited by 152
Evidence of cisplatin-induced senescent-like growth arrest in nasopharyngeal carcinoma cells.
Wang, L., Wong, S. C., Pan, J., Tsao, S. W., Fung, K., Kwong, D., Sham, J. S. T., & Nicholls, J. M. (1998) · PubMed · Cited by 150
The p400 E1A-associated protein is a novel component of the p53 → p21 senescence pathwayPreprint
Chan, H. M., Narita, M., Lowe, S. W., & Livingston, D. M. (2005) · Genes & Development · doi:10.1101/gad.1280205 · Cited by 150
Kim, K. S., Kang, K. W., Seu, Y. B., Baek, S., & Kim, J.-R. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.11.004 · Cited by 146
SOCS1 Links Cytokine Signaling to p53 and Senescence
Calabrese, V., Mallette, F. A., Deschênes‐Simard, X., Ramanathan, S., Gagnon, J., Moores, A., Ilangumaran, S., & Ferbeyre, G. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.044 · Cited by 146
Chen, X., Mitsutake, N., LaPerle, K., Akeno, N., ZANZONICO, P. B., Longo, V. A., Mitsutake, S., Kimura, E. T., Geiger, H., Santos, E., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900343106 · Cited by 144
Shamma, A., Takegami, Y., Miki, T., Kitajima, S., Noda, M., Obara, T., Okamoto, T., & Takahashi, C. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.001 · Cited by 140
Involvement of the Ink4 proteins p16 and p15 in T-lymphocyte senescence
Erickson, S., Sangfelt, O., Heyman, M. M., Castro, J., Einhorn, S., & Grandér, D. (1998) · Oncogene · doi:10.1038/sj.onc.1201965 · Cited by 125
Cellular senescence predicts treatment outcome in metastasised colorectal cancer
Haugstetter, A. M., Loddenkemper, C., Lenze, D., Gröne, J., Standfuß, C., Petersen, I., Dörken, B., & Schmitt, C. A. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605784 · Cited by 117
Predisposition to Neoplastic Transformation Caused by Gene Replacement of H- ras 1
Finney, R. E., & Bishop, J. M. (1993) · Science · doi:10.1126/science.8502998 · Cited by 116
van Riggelen, J., Müller, J., Otto, T., Beuger, V., Yetil, A., Choi, P. S., Kosan, C., Möröy, T., Felsher, D. W., & Eilers, M. (2010) · Genes & Development · doi:10.1101/gad.585710 · Cited by 113
Frequent p16-Independent Inactivation of p14ARF in Human Melanoma
Freedberg, D. E., Rigas, S. H., Russak, J. E., Gai, W., Kaplow, M., Osman, I., Turner, F., Randerson‐Moor, J. A., Houghton, A. N., BUSAM, K. J., et al. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn157 · Cited by 110
Nicke, B., Bastien, J., Khanna, S. J., Warne, P. H., Cowling, V., Cook, S. J., Peters, G., Delpuech, O., Schulze, A., Berns, K., et al. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.10.038 · Cited by 108
Lipid mediators of autophagy in stress-induced premature senescence of endothelial cells
Patschan, S., Chen, J., Polotskaia, A., Mendelev, N., Cheng, J., Patschan, D., & Goligorsky, M. S. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00713.2007 · Cited by 105
Recurrent melanocytic nevi: Clinical and histologic review of 175 cases
Park, H. K., Leonard, D. D., Arlington, J. H., et al. (1987) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(87)70204-7 · Cited by 101
Molecular Regulation of Melanocyte Senescence
Bennett, D. C., & Medrano, E. E. (2002) · Pigment Cell Research · doi:10.1034/j.1600-0749.2002.02036.x · Cited by 99
Olsen, C. L., Gardie, B., Yaswen, P., & Stampfer, M. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205780 · Cited by 96
Mechanisms of Cell-Cycle Arrest in Spitz Nevi with Constitutive Activation of the MAP-Kinase Pathway
Maldonado, J. L., Timmerman, L., Fridlyand, J., & Bastian, B. C. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63736-4 · Cited by 93
Dai, C. Y., Furth, E. E., Mick, R., Koh, J., Takayama, T., Niitsu, Y., & Enders, G. H. (2000) · Gastroenterology · doi:10.1053/gast.2000.17952 · Cited by 92
Kato, D., Miyazawa, K., Ruas, M., Starborg, M., Wada, I., Oka, T., Sakai, T., Peters, G. G., & Hara, E. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00426-8 · Cited by 89
Santoriello, C., Deflorian, G., Pezzimenti, F., Kawakami, K., Lanfrancone, L., di Fagagna, F. D., & Mione, M. (2008) · Disease Models & Mechanisms · doi:10.1242/dmm.001016 · Cited by 88
p16INK4a inactivation is not required to immortalize human mammary epithelial cells
Herbert, B., Wright, W. E., & Shay, J. W. (2002) · Oncogene · doi:10.1038/sj.onc.1205902 · Cited by 86
Oncogene-Induced Senescence Does Not Require the p16INK4a or p14ARF Melanoma Tumor Suppressors
Haferkamp, S., Scurr, L. L., Becker, T. M., Frausto, M., Kefford, R. F., & Rizos, H. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.5 · Cited by 81
Molecular mechanisms of replicative senescence in endothelial cells
Foreman, K. E., & Tang, J. M. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.09.005 · Cited by 81
Real-time in vivo imaging of P16[INK]⁴[a] reveals cross talk with p53
Hara, E. (2010) · Medical Entomology and Zoology · Cited by 72
Dilley, T. K., Bowden, G. T., & Chen, Q. M. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00308-2 · Cited by 64 · cited 2×
“In certain settings, pro-oncogenic effects result: The proliferative rate, migration, and invasion of premalignant cells are enhanced when they are cocultured with, or grown in medium conditioned by, senescent fibroblasts (Krtolica et al. 2001; Dilley et al. 2003; Parrinello et al. 2005; Yang et al. 2006).”
BackgroundLimited Role of Murine ATM in Oncogene-Induced Senescence and p53-Dependent Tumor Suppression
Efeyan, A., Murga, M., Martínez-Pastor, B., Ortega-Molina, A., Soria, R., Collado, M., Fernández-Capetillo, Ó., & Serrano, M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005475 · Cited by 63
IGFBP7 Is Not Required for B-RAF-Induced Melanocyte Senescence
Scurr, L. L., Pupo, G. M., Becker, T. M., Lai, K., Schrama, D., Haferkamp, S., Irvine, M., Scolyer, R. A., Mann, G. J., Becker, J. C., et al. (2010) · Cell · doi:10.1016/j.cell.2010.04.021 · Cited by 62
‘Senescence‐associated’ β‐galactosidase activity in the upper gastrointestinal tract
Going, J. J., Stuart, R. C., Downie, M., Fletcher‐Monaghan, A. J., & Keith, W. N. (2002) · The Journal of Pathology · doi:10.1002/path.1059 · Cited by 61
The Recurrence of Nevi After Incomplete Removal
Schoenfeld, R. J. (1958) · A M A Archives of Dermatology · doi:10.1001/archderm.1958.01560070032004 · Cited by 59
Goldstein, S., Moerman, E. J., Fujii, S., & Sobel, B. E. (1994) · Journal of Cellular Physiology · doi:10.1002/jcp.1041610321 · Cited by 59
Tissue-specific p19 Arf regulation dictates the response to oncogenic K-ras
Young, N. P., & Jacks, T. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004796107 · Cited by 59
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
