Mechanisms of cellular senescence in human and mouse cells.

Itahana, Koji; Campisi, Judith; Dimri, Goberdhan P.

doi:10.1023/b:bgen.0000017682.96395.10

Cited by 340Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsCancer-related Molecular Pathways

The DOI matches its Crossref record; 82 of the 83 references it cites were found in a registry or an index.

Mechanisms of cellular senescence in human and mouse cells.

Itahana, Koji, Campisi, Judith, Dimri, Goberdhan P.·2004·Biogerontology

DOI 10.1023/b:bgen.0000017682.96395.10

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Abstract

Telomere erosion is considered to be the main cause of the onset of replicative senescence. However, recent findings suggest that a senescent phenotype can be induced by a variety of other stimuli that act independently of telomeres. Moreover, telomere-dependent replicative senescence depends on the species of cell origin, in particular whether cells are of human or rodent origin. In addition, the tissue of origin may also dictate the pathway by which cells undergo replicative senescence. In this Review article, we categorize cellular senescence into two types, which for simplicity we term intrinsic or extrinsic senescence, focus on the differences between human and mouse cells, and discuss the roles of the p53 and pRb tumor suppressor pathways in cellular senescence.

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In vitro cultivated senescent MEFs manifest upregulation of Cdkn1a, Cdkn2a, Lmnb1, Mki67, and other conventional senescence markers.
“Previous studies illustrated that in vitro cultivated senescent MEFs manifested upregulation of Cdkn1a (encoding p21), Cdkn2a (encoding p16), Lmnb1, Mki67, and other conventional senescence markers (Sherr and Dipinho, 2000; Parrinello et al., 2003; Itahana et al., 2004).”
From Single-Cell Transcriptome Analysis Reveals Six Subpopulations Reflecting Distinct Cellular Fates in Senescent Mouse Embryonic Fibroblasts (2020) · cites this paper as Itahana et al., 2004
MEFs derived from M. musculus possess long telomeres and easily detectable telomerase activity.
“MEFs derived from M. musculus possess long telomeres and easily detectable telomerase activity (Itahana et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Itahana et al., 2004
In many primary human cell lines, replicative senescence occurs secondary to attrition of telomeres, in a process termed intrinsic senescence.
“In many primary human cell lines, replicative senescence occurs secondary to attrition of the ends of the chromosomes, the telomeres, in a process termed “intrinsic senescence” (Itahana et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Itahana et al., 2004
Senescent cells accumulate in vivo in mammals with increasing age and at sites of pathology.
“senescent cells accumulate in vivo in mammals with increasing age and at sites of pathology (Itahana et al., 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Itahana et al., 2004

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Sorted by citations

Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
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Biochemistry of oxidative stress
Halliwell, B. B. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351147 · Cited by 1,591
Oxidative stress and cancer: Have we moved forward?
Halliwell, B. (2007) · Biochemical Journal · doi:10.1042/bj20061131 · Cited by 1,302
DNA Repair, Genome Stability, and Aging
Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W. (2005) · Cell · doi:10.1016/j.cell.2005.01.028 · Cited by 944
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix
Loeser, R. F. (2009) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2009.03.002 · Cited by 726
Why is osteoarthritis an age-related disease?
Anderson, A. S., & Loeser, R. F. (2010) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2009.08.006 · Cited by 719
“However, extrinsic or stress-induced senescence that occurs from diverse stimuli including oxidative damage, activated oncogenes, and inflammation can also damage telomeres [60,62] and is a much more likely mechanism for senescence in cartilage [63].”
Background
Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase
Wang, I.-C., Chen, Y.-J., Hughes, D., Petrovic, V., Major, M. L., Park, H. J., Tan, Y., Ackerson, T., & Costa, R. H. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10875-10894.2005 · Cited by 627
“Recent studies report that MEFs cultured in vitro, under atmospheric oxygen concentrations, show rapid “cellular senescence,” and passage 3 MEFs exhibit an increase in mutations and undergo immortalization (8, 25, 72).”
Background
Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis
Grootaert, M. O. J., Moulis, M., Roth, L., Martinet, W., Vindis, C., Bennett, M. R., & De Meyer, G. R. Y. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy007 · Cited by 606
Aging and Genome Maintenance: Lessons from the Mouse?
Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H., & Vijg, J. (2003) · Science · doi:10.1126/science.1079161 · Cited by 553
Self-citation
Methods to Detect Biomarkers of Cellular Senescence
Itahana, K., Campisi, J., & Dimri, G. P. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-361-5_3 · Cited by 535
Self-citation
A computational solution for bolstering reliability of epigenetic clocks: implications for clinical trials and longitudinal tracking
Higgins-Chen, A. T., Thrush, K. L., Wang, Y., Minteer, C. J., Kuo, P.-L., Wang, M., Niimi, P., Sturm, G., Lin, J., Moore, A. Z., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00248-2 · Cited by 502
Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?
Akbar, A. N., & Henson, S. M. (2011) · Nature Reviews Immunology · doi:10.1038/nri2959 · Cited by 474
“There are also considerable differences in the regulation of senescence in rodents and human”
Background
A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.
Coppé, J.-P., Patil, C. K., Rodier, F., Krtolica, A., Beauséjour, C. M., Parrinello, S., Hodgson, J. G., Chin, K., Desprez, P.-Y., & Campisi, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009188 · Cited by 455
“Moreover, mouse, but not human, cells often spontaneously immortalize in culture [39,40,41].”
BackgroundSelf-citation
The Gene Expression Program of Prostate Fibroblast Senescence Modulates Neoplastic Epithelial Cell Proliferation through Paracrine Mechanisms
Bavik, C., Coleman, I., Dean, J. P., Knudsen, B., Plymate, S., & Nelson, P. S. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1716 · Cited by 453
“Several factors have been shown to induce a phenotype of cellular senescence (23, 24).”
Background
Age-Related Changes in the Musculoskeletal System and the Development of Osteoarthritis
Loeser, R. F. (2010) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.03.002 · Cited by 465
Human cell senescence as a DNA damage response
Zglinicki, T. V., Saretzki, G., Ladhoff, J., Fagagna, F. D. D., & Jackson, S. P. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.09.034 · Cited by 419
“Finally, they allow the possibility of viewing cellular senescence in all its forms including telomere-dependent and -independent senescence, as one common type of cellular stress response, in a way comparable to apoptosis (von Zglinicki, 2001, 2002, 2003; Campisi, 2003; Ben-Porath and Weinberg, 2004; Itahana et al.,…”
Background
Critical pathways in cellular senescence and immortalization revealed by gene expression profiling
Fridman, A. L., & Tainsky, M. A. (2008) · Oncogene · doi:10.1038/onc.2008.213 · Cited by 385
“The differences between the mechanisms of human and mouse cell immortalization have been reviewed in Itahana et al. (2004).”
Background
Effects of aging on articular cartilage homeostasis
Lotz, M., & Loeser, R. F. (2012) · Bone · doi:10.1016/j.bone.2012.03.023 · Cited by 393
“Besides replicative senescence, telomere shortening can be seen as a result of extrinsic or “stress-induced” senescence [99, 100].”
Background
Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation
Inomata, K., Aoto, T., Binh, N. T., Okamoto, N., Tanimura, S., Wakayama, T., Iseki, S., Hara, E., Masunaga, T., Shimizu, H., et al. (2009) · Cell · doi:10.1016/j.cell.2009.03.037 · Cited by 368
“p53 or p16-Rb pathways have been implicated in the fate determination of cells under genotoxic stress including IR (Itahana et al., 2004; Sharpless and DePinho, 2007).”
Telomeres: Cancer to Human Aging
Stewart, S. A., & Weinberg, R. A. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104518 · Cited by 348
“To explain these apparent discrepancies, some suggested that murine cells were more sensitive to in vitro growth conditions that resulted in nontelomeric damage and a distinct type of senescence often termed stressinduced senescence (Itahana et al. 2004).”
Background
What has senescence got to do with cancer?
Dimri, G. P. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.025 · Cited by 323
“Using the SA-β-gal marker, and other senescence and aging biomarkers, several recent studies have demonstrated a role for cellular senescence in aging and cancer (reviewed in Itahana et al., 2004; Campisi, 2005; Lombard et al., 2005).”
BackgroundInfluentialSelf-citation
Metastasis: cancer cell’s escape from oxidative stress
Pani, G., Galeotti, T., & Chiarugi, P. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9225-4 · Cited by 328
“Replicative senescence limits proliferation of initiated cells and may occur even before critical telomere shortening as a consequence of DNA damage or oncogenic signaling [146], and is triggered by a p53 and p16 dependent cascade [147].”
Background
Superoxide Radicals in the Execution of Cell Death
Fujii, J., Homma, T., & Osaki, T. (2022) · Antioxidants · doi:10.3390/antiox11030501 · Cited by 332
Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence
Swanson, E. C., Manning, B., Zhang, H., & Lawrence, J. B. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201306073 · Cited by 251
Significant Role for p16INK4a in p53-Independent Telomere-Directed Senescence
Jacobs, J. J. L., & de Lange, T. (2004) · Current Biology · doi:10.1016/j.cub.2004.12.025 · Cited by 237
Progressive loss of SIRT1 with cell cycle withdrawal
Sasaki, T., Maier, B., Bartke, A., & Scrable, H. J. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00235.x · Cited by 235
“Senescent cells accumulate in vivo as the organism ages, as well as at sites of pathology (Itahana et al ., 2004).”
Background
Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence
Wiel, C., Lallet-Daher, H., Gitenay, D., Gras, B., Le Calvé, B., Augert, A., Ferrand, M., Prevarskaya, N., Simonnet, H., Vindrieux, D., et al. (2014) · Nature Communications · doi:10.1038/ncomms4792 · Cited by 231
Age‐related impairment of mesenchymal progenitor cell function
Stolzing, A., & Scutt, A. M. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00213.x · Cited by 219
“Unlike apoptosis, which eliminates damaged cells from tissues, senescent cells remain alive despite changes in morphology, metabolism, and derangement of differentiated functions (Itahana et al., 2004).”
Background
Expression of the p16INK4A Gene Is Associated Closely with Senescence of Human Mesenchymal Stem Cells and Is Potentially Silenced by DNA Methylation During In Vitro Expansion
Shibata, K. R., Aoyama, T., Shima, Y., Fukiage, K., Otsuka, S., Furu, M., Kohno, Y., Ito, K., Fujibayashi, S., Neo, M., et al. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0225 · Cited by 222
The Age-Related Changes in Cartilage and Osteoarthritis
Li, Y., Wei, X., Zhou, J., & Lei, W. (2013) · BioMed Research International · doi:10.1155/2013/916530 · Cited by 196
“However, the senescence in articular cartilage seems more relevant to the “extrinsic senescence” or stress-induced senescence, which occurs in response to telomere-damaging stimuli, including oxidative damage, activated oncogenes, and inflammation [113, 115] and is a muchmore likely mechanism for senescence in cartila…”
Background
Continuous elimination of oxidized nucleotides is necessary to prevent rapid onset of cellular senescence
Rai, P., Önder, T. T., Young, J. J., McFaline‐Figueroa, J. L., Pang, B., Dedon, P. C., & Weinberg, R. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809834106 · Cited by 185
“This was consistent with the notion that the tumor suppressor pathways that mediate replicative senescence (31) also regulate shMTH1-induced senescence.”
Background
Hsp70–Bag3 Interactions Regulate Cancer-Related Signaling Networks
Colvin, T. A., Gabai, V. L., Gong, J., Calderwood, S. K., Li, H., Gummuluru, S., Matchuk, O. N., Smirnova, S. G., Orlova, N. V., Александровна, З. И., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0747 · Cited by 185
“Senescence is defined as irreversible cell growth arrest that is associatedwith assorted cellular changes inmorphology and gene expression (14, 15).”
Background
The Transcription Factor FOXM1 (Forkhead box M1)
Wierstra, I. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407173-5.00004-2 · Cited by 180
Both telomeric and non-telomeric DNA damage are determinants of mammalian cellular senescence
Nakamura, A. J., Chiang, Y. J., Hathcock, K. S., Horikawa, I., Sedelnikova, O. A., Hodes, R. J., & Bonner, W. M. (2008) · Epigenetics & Chromatin · doi:10.1186/1756-8935-1-6 · Cited by 168
“It has been shown that normoxic conditions are stressful to MEF growth, leading to earlier senescence, which can be lessened by growth in 3% O2 [16,19].”
Background
Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival
Kang, M., Kim, R. H., Kim, S. J., Yip, F. K., Shin, K.-H., Dimri, G. P., Christensen, R. E., Han, T., & Park, N.-H. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603529 · Cited by 164
“The onset of extrinsic senescence is frequently associated with induction of p16INK4A (Itahana et al, 2004).”
BackgroundInfluentialSelf-citation
ROS Fusion Tyrosine Kinase Activates a SH2 Domain–Containing Phosphatase-2/Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Signaling Axis to Form Glioblastoma in Mice
Charest, A., Wilker, E., McLaughlin, M. E., Lane, K. M., Gowda, R., Coven, S., McMahon, K., Kovach, S., Feng, Y., Yaffe, M. B., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1193 · Cited by 165
The Loss of a Single Telomere Can Result in Instability of Multiple Chromosomes in a Human Tumor Cell Line
Sabatier, L., Ricoul, M., Pottier, G., & Murnane, J. P. (2005) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-04-0194 · Cited by 160
“(Mol Cancer Res 2005;3(3):139–50) Introduction”
BackgroundMethod
Cytotoxic CD4 + T Cells Eliminate Senescent Cells by Targeting Commensal Cytomegalovirus Antigen
Hasegawa, T., Oka, T., Son, H. G., Oliver-Garcia, V. S., Azin, M., Eisenhaure, T., Lieb, D., Hacohen, N., & Demehri, S. (2022) · Cell · doi:10.1016/j.cell.2023.02.033 · Cited by 163
Faces of cellular senescence in skin aging
Ho, C. Y., & Dreesen, O. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111525 · Cited by 170
“Likewise, careful interpretation is needed regarding cellular senescence in studies using murine cells as a model of human senescence, as there are fundamental differences between human and mouse, particularly in terms of telomere-dependent replicative senescence and oxygen sensitivity (Coppe et al., 2010; Itahana et…”
Background
Catabolic stress induces features of chondrocyte senescence through overexpression of caveolin 1: Possible involvement of caveolin 1–induced down‐regulation of articular chondrocytes in the pathogenesis of osteoarthritis
Dai, S., Shan, Z., Nakamura, H., Masuko, K., Kato, T., Nishioka, K., & Yudoh, K. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21639 · Cited by 160
Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease
Sis, B., Tasanarong, A., Khoshjou, F., Dadras, F., Solez, K., & Halloran, P. F. (2007) · Kidney International · doi:10.1038/sj.ki.5002039 · Cited by 159
Mammary epithelial cell transformation: insights from cell culture and mouse models
Dimri, G. P., Band, H., & Band, V. (2005) · Breast Cancer Research · doi:10.1186/bcr1275 · Cited by 164
“Much of our knowledge about senescence comes from studies conducted in human fibroblasts [ 30-34 ].”
BackgroundInfluentialSelf-citation
Oxygen tension controls the expansion of human CNS precursors and the generation of astrocytes and oligodendrocytes
Pistollato, F., Chen, H.-L., Schwartz, P. H., Basso, G., & Panchision, D. M. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.04.003 · Cited by 165
“, 2000) or exerted a protective anti-oxidant effect that limits apoptosis or senescence of these cells (Itahana et al., 2004; Limoli et al., 2004;Madhavan et al., 2006).”
Background
Telomerase, senescence and ageing
Shawi, M., & Autexier, C. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.11.007 · Cited by 160
Roles of FGF signaling in stem cell self-renewal, senescence and aging
Coutu, D. L., & Galipeau, J. (2011) · Aging · doi:10.18632/aging.100369 · Cited by 161
“Indeed, mice lacking telomerase activity only show signs of accelerated aging after six generations[6].”
Background
Oxidative stress, cellular senescence and ageing
Pole, A., Dimri, M., & Dimri, G. P. (2016) · AIMS molecular science · doi:10.3934/molsci.2016.3.300 · Cited by 168
“flattened morphology but are metabolically active [78].”
Self-citation
Extracellular Vesicles from Adipose‐Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts
Tofiño-Vian, M., Guillén, M. I., del Caz, M. D. P., Castejón, M. A., & Alcaraz, M. J. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/7197598 · Cited by 158
“Therefore, oxidative stress induces telomere-independent senescence leading to cell dysfunction [30].”
Background
p53 Mediates the Accelerated Onset of Senescence of Endothelial Progenitor Cells in Diabetes
Rosso, A., Balsamo, A., Gambino, R., Dentelli, P., Falcioni, R., Cassader, M., Pegoraro, L., Pagano, G., & Brizzi, M. F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509293200 · Cited by 152
Oxygen Tension Regulates Survival and Fate of Mouse Central Nervous System Precursors at Multiple Levels
Chen, H.-L., Pistollato, F., Hoeppner, D. J., Ni, H.-T., McKay, R. D. G., & Panchision, D. M. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0609 · Cited by 152
Defective autophagy in atherosclerosis: to die or to senesce?
Grootaert, M. O. J., Roth, L., Schrijvers, D. M., De Meyer, G. R. Y., & Martinet, W. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7687083 · Cited by 147
“Although senescence in mice can be regulated differently to humans [64, 65], we cannot exclude the possibility that the increased collagen content could be related to the activation of other cellular pathways, rather than being part of the senescent phenotype itself.”
Background
Mechanisms of Lung Fibrosis Resolution
Glasser, S. W., Hagood, J. S., Wong, S. S., Taype, C. A., Madala, S. K., & Hardie, W. D. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.01.018 · Cited by 151
“Extrinsic senescence develops after cellular damage or stress and is hypothesized to be an important mechanism to constrain the malignant progression of tumor cells.(79) Replicative senescence is an intrinsic mechanism whereby there is a limitation in the number of times that cells can divide and is believed to contri…”
Background
The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury
Fan, H. X., Yang, H., Li, Y., Wang, Y., He, W., & Hao, C. (2013) · Kidney International · doi:10.1038/ki.2012.394 · Cited by 147
Primary laminopathy fibroblasts display altered genome organization and apoptosis
Meaburn, K. J., Cabuy, E., Bonne, G., Lévy, N., Morris, G. E., Novelli, G., Kill, I. R., & Bridger, J. M. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00270.x · Cited by 155
“, 2004) and is central in initiating cellular senescence in combination with p16 (Thomas et al., 2003; Itahana et al., 2004), we assessed the fraction of cells displaying forms of pRb associated with all cells and with only proliferating cells.”
Background
Stem cells, senescence, neosis and self-renewal in cancer.
Rajaraman, R., Guernsey, D. L., Rajaraman, M. M., & Rajaraman, S. R. (2006) · Cancer Cell International · doi:10.1186/1475-2867-6-25 · Cited by 152
“As described above, in primary cells, induction of an accelerated senescent phase acts as an efficient tumor suppressor mechanism; and DNA damaging agents or genotoxins also elicit an accelerated senescence-like phenotype [Reviewed in [114-116]] by activating DNA damage response pathways [88].”
Background
Mel-18, a Polycomb Group Protein, Regulates Cell Proliferation and Senescence via Transcriptional Repression of Bmi-1 and c-Myc Oncoproteins
Guo, W., Datta, S., Band, V., & Dimri, G. P. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-05-0447 · Cited by 146
“It is regulated by an array of growth regulators including polycomb group (PcG) proteins (reviewed in Itahana et al., 2004).”
BackgroundSelf-citation
Coevolution of telomerase activity and body mass in mammals: From mice to beavers
Gorbunova, V. A., & Seluanov, A. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.02.008 · Cited by 143
“If mouse cells are grown at atmospheric oxygen concentration (20%), which provides an additional oxidative stress to the cells, cell growth slows after 12– 15 PDs, but within a few days immortal clones emerge and continue to grow (Parrinello et al., 2003; Itahana et al., 2004).”
Background
Geroconversion: irreversible step to cellular senescence
Blagosklonny, M. V. (2014) · Cell Cycle · doi:10.4161/15384101.2014.985507 · Cited by 147
“As a powerful inducer of arrest, p53 is involved in stress-induced, oncogene-induced and replicative senescence.(6,9,55,56,61-63) p53 “induces” senescence by causing cell cycle arrest, while failing to inhibit mTOR.”
Background
Colorimetric Detection of Senescence-Associated β Galactosidase
Itahana, K., Itahana, Y., & Dimri, G. P. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-239-1_8 · Cited by 142
“Telomeres become shortened at each round of cell division and, when they reach the critical length for replication, cells are permanently arrested with a G1 DNA content in a state called replicative senescence or cellular senescence (4, 5).”
Self-citation
Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro
Wright, L. S., Prowse, K. R., Wallace, K., Linskens, M. H. K., & Svendsen, C. N. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.03.012 · Cited by 134
“The telomere hypothesis predicts that all somatic cells eventually senesce due to chromosomal end replication problems caused by telomeric erosion and/or uncapping (for review, see [3 – 5]).”
Background
Cancer and aging: the importance of telomeres in genome maintenance
Rodier, F., Kim, S.-H., Nijjar, T., Yaswen, P., & Campisi, J. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.10.012 · Cited by 132
“In either case, when present, p53 is crucial for mediating the cellular response to telomere dysfunction [9, 18, 109, 111, 116, 117] (Fig.”
BackgroundSelf-citation
Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas
Lallemand, D., Manent, J., Couvelard, A., Watilliaux, A., Siena, M., Chareyre, F., Lampin-Saint-Amaux, A., Niwa‐Kawakita, M., Kalamarides, M., & Giovannini, M. (2008) · Oncogene · doi:10.1038/onc.2008.427 · Cited by 134
“Primary mouse cells can escape this fate by losing expression of tumor suppressor genes, such as p21Cip, p53 or pRb (Bringold and Serrano, 2000; Itahana et al., 2004).”
Stem Cell Self-Renewal and Cancer Cell Proliferation Are Regulated by Common Networks That Balance the Activation of Proto-oncogenes and Tumor SuppressorsPreprint
Pardal, R., Molofsky, A. V., He, S., & Morrison, S. J. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.057 · Cited by 133
“Bmi-1 overexpression, in contrast, can bypass senescence and extend the replicative life span of primary cells by reducing p16Ink4a and p19Arf expression (Jacobs et al. 1999a; Dimri et al. 2002; Itahana et al. 2003).”
Background
ROC1/RBX1 E3 Ubiquitin Ligase Silencing Suppresses Tumor Cell Growth via Sequential Induction of G2-M Arrest, Apoptosis, and Senescence
Jia, L., Soengas, M. S., & Sun, Y. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4671 · Cited by 128
“Senescence is mainly regulated by two tumor suppressor pathways: p53/p21 and p16/pRB (22, 42, 43).”
Cellular senescence: a promising strategy for cancer therapy
Lee, S., & Lee, J. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.1.294 · Cited by 117
Senescent T cells within suppressive tumor microenvironments: emerging target for tumor immunotherapy
Liu, X., Hoft, D. F., & Peng, G. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133679 · Cited by 116
“org Volume 130 Number 3 March 2020 replicative senescence (telomere-dependent senescence), which occurs due to telomere shortening and/or dysfunctional telomerase that trigger a classical DNA-damage response (91, 92), contributes to aging and age-related pathologies in vivo (93).”
Background
Premature senescence of endothelial cells: Methusaleh's dilemma
Chen, J., & Goligorsky, M. S. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01103.2005 · Cited by 112
“In mouse embryo fibroblasts, these pathways may function independently, whereas both pathways may be involved in human fibroblasts (42, 76).”
Background
Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase
Jin, Y., Kato, T., Furu, M., Nasu, A., Kajita, Y., Mitsui, H., Ueda, M., Aoyama, T., Nakayama, T., Nakamura, T., et al. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.12.096 · Cited by 111
“Cellular senescence is induced by both intrinsic and extrinsic factors [5].”
Background
Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low‐Grade Inflammation in Osteoarthritis
Minguzzi, M., Cetrullo, S., D’Adamo, S., Silvestri, Y., Flamigni, F., & Borzı̀, R. M. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/3075293 · Cited by 113
“Indeed, since the ends of chromosomes are particularly sensitive to oxidative stress, this can result in telomere shortening similar to that seen with replicative senescence [97, 98].”
Statin prevents chondrocyte aging and degeneration of articular cartilage in osteoarthritis (OA)
Yudoh, K., & Karasawa, R. (2010) · Aging · doi:10.18632/aging.100213 · Cited by 105
“There is a general consensus that extrinsic senescence is induced by several types of stress, such as oxidative stress or proinflammatory cytokines [21-23].”
Background
Biology of Aging and Cancer
Anisimov, V. N. (2007) · Cancer Control · doi:10.1177/107327480701400104 · Cited by 114
miR-127 Regulates Cell Proliferation and Senescence by Targeting BCL6
Chen, J., Wang, M., Guo, M., Xie, Y., & Cong, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080266 · Cited by 102
“Cellular senescence occurs in culture and in vivo as a response to extracellular and intracellular stresses, including telomere dysfunction, DNA damage caused by radiation or chemicals, and oncogenic or mitogenic stimuli [2,3].”
Background
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Authors: Itahana, K., Campisi, J., & Dimri, G. P.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Lawrence Berkeley National Laboratory (US)
Corresponding author: Dimri, Goberdhan P.
ORCID: Itahana, Koji
Campisi, Judith
Dimri, Goberdhan P.
Venue: Biogerontology
Publisher: Springer Science and Business Media LLC
Published: 2004-02
Volume: 5
Issue: 1
Pages: 1-10
ISSN: 1389-5729 (ISSN-L)
1573-6768
DOI: 10.1023/b:bgen.0000017682.96395.10
OpenAlex: W2036676765
Cited by: 338
References: 83
Citations by year: 2026: 5 · 2025: 7 · 2024: 4 · 2023: 9 · 2022: 19 · 2021: 11 · 2020: 13 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 16 · 2015: 14 · 2014: 13 · 2013: 23 · 2012: 19
FWCI: 2.63
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Biogerontology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging
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, telomere shortening, p53 pathway, pRb pathway, tumor suppressor pathways, tissue of origin, senescence mechanisms
MeSH terms: Animals, Humans, Nuclear Proteins, Proto-Oncogene Proteins, Repressor Proteins, Tumor Suppressor Protein p53, Retinoblastoma Protein, Telomere, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Mice, Polycomb Repressive Complex 1

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Mechanisms of cellular senescence in human and mouse cells.

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