Cellular senescence: a link between cancer and age-related degenerative disease?
Open accessAbstract
Cellular senescence is an established cellular stress response that acts primarily to prevent the proliferation of cells that experience potentially oncogenic stress. In recent years, it has become increasingly apparent that the senescence response is a complex phenotype, which has a variety of cell non-autonomous effects. The senescence-associated secretory phenotype, or SASP, entails the secretion of numerous cytokines, growth factors and proteases. The SASP can have beneficial or detrimental effects, depending on the physiological context. One recently described beneficial effect is to aid tissue repair. Among the detrimental effects, the SASP can disrupt normal tissue structures and function, and, ironically, can promote malignant phenotypes in nearby cells. These detrimental effects in many ways recapitulate the degenerative and hyperplastic pathologies that develop during aging. Because the SASP is largely a response to genomic or epigenomic damage, we suggest it may be a model for a cellular damage response that can propagate damage signals both within and among tissues. We propose that both the degenerative and hyperplastic diseases of aging may be fueled by such damage signals.
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The secretion of these inflammatory proteins by senescent cells is predicted to cause chronic inflammation locally and possibly systemically.
“The secretion of these and similar proteins by senescent cells is predicted to cause chronic inflammation, at least locally and possibly systemically (91–93, 107).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [91]
In most cases, senescent cells have been shown or hypothesized to drive degenerative changes largely through secreted proteins, i.e., the SASP.
“In most cases, senescent cells have been shown or hypothesized to drive degenerative changes largely through secreted proteins—that is, through the SASP (91).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [91]
Recent findings have uncovered an additional beneficial effect of the senescence response and accompanying SASP: the ability to promote optimal repair of damaged tissue.
“Recent findings have uncovered an additional beneficial effect of the senescence response and accompanying SASP: the ability to promote optimal repair of damaged tissue (59, 91, 145–147).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [91]
Cellular senescence can compromise tissue repair and regeneration, thereby contributing toward aging.
“Cellular senescence can compromise tissue repair and regeneration, thereby contributing toward aging.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Campisi et al., 2011
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Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Jemal, A., Siegel, R., Xu, J., & Ward, E. (2010) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20073 · Cited by 12,596 · see citing works
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 · see citing works
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 · see citing works
Self-citationDNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
Bartkova, J., Hořejší, Z., Koed, K., Krämer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J. M., Lukas, C., et al. (2005) · Nature · doi:10.1038/nature03482 · Cited by 2,688 · see citing works
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 · see citing works
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 2,359 · see citing works
Self-citationThe microenvironment of the tumour–host interface
Liotta, L. A., & Kohn, E. C. (2001) · Nature · doi:10.1038/35077241 · Cited by 2,322 · see citing works
Rejuvenation of aged progenitor cells by exposure to a young systemic environment
Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005) · Nature · doi:10.1038/nature03260 · Cited by 2,287 · see citing works
Persistent 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 · see citing works
Self-citationBissell, M. J., & Radisky, D. (2001) · Nature Reviews Cancer · doi:10.1038/35094059 · Cited by 2,180 · see citing works
Oncogene-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 2× · see citing works
“Important features of the SASP include the fact that it is conserved between human and mouse cells [33], occurs in a variety of proliferative cell types (fibroblasts, epithelial cells, endothelial cells, astrocytes, etc) [29, 34, 35], and occurs in vivo in both mice and humans [27, 29, 31, 32].”
BackgroundSenescence 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.2008.06.049 · Cited by 2,029 · see citing works
Senescence 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
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,016 · cited 1× · see citing works
“In addition, the SASP may function to stimulate the regeneration and/or repair of tissues after damage [42, 43].”
BackgroundSelf-citationAn Oncogene-Induced DNA Damage Model for Cancer Development
Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008) · Science · doi:10.1126/science.1140735 · Cited by 1,851 · see citing works
Chemokine 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 1× · see citing works
“Important features of the SASP include the fact that it is conserved between human and mouse cells [33], occurs in a variety of proliferative cell types (fibroblasts, epithelial cells, endothelial cells, astrocytes, etc) [29, 34, 35], and occurs in vivo in both mice and humans [27, 29, 31, 32].”
BackgroundKirkwood, T. B. L., & Austad, S. N. (2000) · Nature · doi:10.1038/35041682 · Cited by 1,774 · see citing works
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 · see citing works
Self-citationIncreased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis
Brack, A. S., Conboy, M. J., Roy, S., Lee, M., Kuo, C. J., Keller, C., & Rando, T. A. (2007) · Science · doi:10.1126/science.1144090 · Cited by 1,564 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
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 · see citing works
Self-citationInflammatory networks during cellular senescence: causes and consequences.
Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.03.003 · Cited by 1,354 · see citing works
Self-citationChronic stress and age-related increases in the proinflammatory cytokine IL-6.
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Malarkey, W. B., & Glaser, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1531903100 · Cited by 1,220 · cited 1× · see citing works
“For example, the SASPs of senescent or damaged cells in the skin, which increase with age [65,78,79], might cause or contribute to the age-related rise in circulating inflammatory cytokines such as IL-6, which, in turn, are thought to promote a variety of chronic degenerative diseases, as well as cancer [80–82].”
BackgroundManolagas, S. C. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0024 · Cited by 1,210 · see citing works
Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106 · see citing works
Fat tissue, aging, and cellular senescence
Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · see citing works
Freund, A., Patil, C. K., & Campisi, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.69 · Cited by 1,039 · see citing works
Self-citationNon–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008 · see citing works
p16INK4a induces an age-dependent decline in islet regenerative potential
Krishnamurthy, J., Ramsey, M. R., Ligon, K. L., Torrice, C., Koh, A., Bonner-Weir, S., & Sharpless, N. E. (2006) · Nature · doi:10.1038/nature05092 · Cited by 1,003 · cited 1× · see citing works
“Recently, the age-dependent increase in p16INK4a expression was linked to the declining proliferative capacity of stem cells in the brain, bone marrow and pancreas [66–68] – all three tissues showed signifi-”
BackgroundJun, J.-I., & Lau, L. F. (2010) · Nature Cell Biology · doi:10.1038/ncb2070 · Cited by 998 · see citing works
Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
Molofsky, A. V., Slutsky, S. G., Joseph, N. M., He, S., Pardal, R., Krishnamurthy, J., Sharpless, N. E., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature05091 · Cited by 972 · see citing works
DePinho, R. A. (2000) · Nature · doi:10.1038/35041694 · Cited by 951 · see citing works
Cellular senescence as a tumor-suppressor mechanism
Campisi, J. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)02151-1 · Cited by 936 · see citing works
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 · see citing works
Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all
Gil, J., & Peters, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1987 · Cited by 843 · see citing works
The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer
Naugler, W. E., & Karin, M. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.007 · Cited by 730 · see citing works
Interleukin-6 in Aging and Chronic Disease: A Magnificent Pathway
Maggio, M. G., Guralnik, J. M., Longo, D. L., & Ferrucci, L. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.6.575 · Cited by 687 · see citing works
Orjalo, A. V., Bhaumik, D., Gengler, B. K., Scott, G. K., & Campisi, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905299106 · Cited by 654 · see citing works
Self-citationKortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637 · cited 2× · see citing works
“Finally, the SASP includes factors that help reinforce the tumor suppressive senescence growth arrest [27,30–32].”
BackgroundParrinello, S., Coppe, J.-P., Krtolica, A., & Campisi, J. (2005) · Journal of Cell Science · doi:10.1242/jcs.01635 · Cited by 631 · see citing works
Self-citationSecretion of vascular endothelial growth factor by primary human fibroblasts at senescence
Coppé, J.-P., Kauser, K., Campisi, J., & Beauséjour, C. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603307200 · Cited by 604 · see citing works
Self-citationTherapeutic targeting of the tumor microenvironment
Joyce, J. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.024 · Cited by 580 · see citing works
Evolutionary medicine: from dwarf model systems to healthy centenarians?
Longo, V. D., & Finch, C. E. (2003) · Science · doi:10.1126/science.1077991 · Cited by 575 · see citing works
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 · see citing works
p16 <sup>INK4A</sup> is a robust <i>in vivo</i> biomarker of cellular aging in human skin
Ressler, S., Bartkova, J., Niederegger, H., Bartek, J., Scharffetter‐Kochanek, K., Jansen‐Dürr, P., & Wlaschek, M. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00231.x · Cited by 557 · see citing works
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 · cited 1× · see citing works
“However, the xenograft studies support the idea that -- as both senescent cells and (mutant) premalignant cells accumulate with age [74] -the SASP of senescent cells might stimulate nearby premalignant cells to progress to full blown malignancy (Fig.”
BackgroundSelf-citationRodier, F., Muñoz, D. P., Teachenor, R., Chu, V., Le, O., Bhaumik, D., Coppé, J.-P., Campeau, E., Beauséjour, C. M., Kim, S.-H., et al. (2011) · Journal of Cell Science · doi:10.1242/jcs.071340 · Cited by 535 · see citing works
Self-citationCancer and ageing: rival demons?
Campisi, J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1073 · Cited by 512 · cited 2× · see citing works
“Thus, cellular senescence may be an example of evolutionary antagonistic pleiotropy, suppressing the development of cancer early in life but driving aging and age-related pathology later in life [4].”
BackgroundSelf-citationLiu, Y., Sanoff, H. K., Cho, H., Burd, C. E., Torrice, C., Ibrahim, J. G., Thomas, N. E., & Sharpless, N. E. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00489.x · Cited by 509 · see citing works
Bhaumik, D., Scott, G. K., Schokrpur, S., Patil, C. K., Orjalo, A. V., Rodier, F., Lithgow, G. J., & Campisi, J. (2009) · Aging · doi:10.18632/aging.100042 · Cited by 500 · see citing works
Self-citationLiu, D., & Hornsby, P. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3452 · Cited by 499 · see citing works
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 · see citing works
Self-citationBavik, 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 · see citing works
Roninson, I. B. (2002) · Cancer Letters · doi:10.1016/s0304-3835(01)00847-3 · Cited by 443 · see citing works
Putting the stress on senescence
Serrano, M., & Blasco, M. A. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00278-7 · Cited by 413 · see citing works
Puzzles, promises and a cure for ageing
Vijg, J., & Campisi, J. (2008) · Nature · doi:10.1038/nature07216 · Cited by 407 · see citing works
Self-citationWhen cells get stressed: an integrative view of cellular senescence
Ben-Porath, I., & Weinberg, R. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420663 · Cited by 404 · see citing works
The influence of the microenvironment on the malignant phenotype
Park, C. C., Bissell, M. J., & Barcellos-Hoff, M. H. (2000) · Molecular Medicine Today · doi:10.1016/s1357-4310(00)01756-1 · Cited by 398 · see citing works
Human cancers express mutator phenotypes: origin, consequences and targeting
Loeb, L. A. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3063 · Cited by 394 · see citing works
Cellular senescence as a tumor-suppressor mechanism
Campisi, J. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)82148-6 · Cited by 390 · see citing works
Self-citationCellular senescence: putting the paradoxes in perspective
Campisi, J. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.10.005 · Cited by 368 · see citing works
Self-citationRegulation of cellular senescence by p53
Itahana, K., Dimri, G., & Campisi, J. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02228.x · Cited by 365 · see citing works
Self-citationImmunosenescence: what does it mean to health outcomes in older adults?
McElhaney, J. E., & Effros, R. B. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.05.023 · Cited by 340 · see citing works
Salminen, A., Ojala, J., Kaarniranta, K., Haapasalo, A., Hiltunen, M., & Soininen, H. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07738.x · Cited by 333 · see citing works
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 · see citing works
Tumor-Host Interactions: A Far-Reaching Relationship
McAllister, S. S., & Weinberg, R. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.4257 · Cited by 326 · see citing works
What has senescence got to do with cancer?
Dimri, G. P. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.025 · Cited by 313 · see citing works
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 · see citing works
Self-citationBuford, T. W., Anton, S. D., Judge, A. R., Marzetti, E., Wohlgemuth, S. E., Carter, C. S., Leeuwenburgh, C., Pahor, M., & Manini, T. M. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.04.004 · Cited by 295 · see citing works
Ohtani, N., Yamakoshi, K., Takahashi, A., & Hara, E. (2004) · The Journal of Medical Investigation · doi:10.2152/jmi.51.146 · Cited by 276 · see citing works
Melov, S., Shoffner, J. M., Kaufman, A. E., & Wallace, D. C. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.20.4122 · Cited by 271 · see citing works
Self-citationCellular senescence in vivo: Its relevance in ageing and cardiovascular disease
Erusalimsky, J. D., & Kurz, D. J. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.04.010 · Cited by 252 · see citing works
Cancer and ageing: a nexus at several levels
Balducci, L., & Ershler, W. B. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1675 · Cited by 250 · see citing works
Relative roles of TGF‐β1 and Wnt in the systemic regulation and aging of satellite cell responses
Carlson, M. E., Conboy, M. J., Hsu, M., Barchas, L., Jeong, J., Agrawal, A., Mikels, A. J., Agrawal, S., Schaffer, D. V., & Conboy, I. M. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00517.x · Cited by 244 · see citing works
Reactive Oxygen Species as Mediators of Cellular Senescence
Colavitti, R., & Finkel, T. (2005) · IUBMB Life · doi:10.1080/15216540500091890 · Cited by 242 · see citing works
Senescence‐associated intrinsic mechanisms of osteoblast dysfunctions
Kassem, M., & Marie, P. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00669.x · Cited by 228 · see citing works
Cell cycle arrest is not senescence
Blagosklonny, M. V. (2011) · Aging · doi:10.18632/aging.100281 · Cited by 217 · see citing works
Stress-induced senescence in human and rodent astrocytes
Bitto, A., Sell, C., Crowe, E., Lorenzini, A., Malaguti, M., Hrelia, S., & Torres, C. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.06.021 · Cited by 204 · see citing works
Vascular smooth muscle cell senescence in atherosclerosis
GORENNE, I., KAVURMA, M., SCOTT, S., & BENNETT, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.06.004 · Cited by 196 · cited 1× · see citing works
“The proinflammatory SASP of senescent endothelial cells has also been proposed to contribute to cardiovascular disease by initiating and fueling the development of atherosclerotic lesions [35, 58].”
BackgroundGenome changes and gene expression in human solid tumors
Gray, J. W., & Collins, C. C. (2000) · Carcinogenesis · doi:10.1093/carcin/21.3.443 · Cited by 195 · see citing works
Tsai, K. K. C., Chuang, E. Y.-Y., Little, J. B., & Yuan, Z.-M. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0703 · Cited by 145 · see citing works
Tumors induce complex DNA damage in distant proliferative tissues in vivo
Redon, C. E., Dickey, J. S., Nakamura, A., Kareva, I., Näf, D., Nowsheen, S., Kryston, T. B., Bonner, W. M., Georgakilas, A. G., & Sedelnikova, O. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008260107 · Cited by 143 · see citing works
Oxygen free radicals in cell senescence: Are they signal transducers?
Passos, J. F., & Von Zglinicki, T. (2006) · Free Radical Research · doi:10.1080/10715760600917151 · Cited by 122 · see citing works
Burton, D. G. A., Matsubara, H., & Ikeda, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.07.005 · Cited by 121 · see citing works
Knudson, A. G. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.1 · Cited by 110 · see citing works
McCullough, K. D., Coleman, W. B., Smith, G. J., & Grisham, J. W. (1997) · PubMed · Cited by 74 · see citing works
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 1× · see citing works
“Although the senescence growth arrest is clearly tumor suppressive, there is mounting evidence that the SASP can promote malignant phenotypes in culture and tumor growth in vivo [28,29,69–73] (Fig.”
BackgroundUpdate on paraneoplastic neurological syndromes
Didelot, A., & Honnorat, J. (2009) · Current Opinion in Oncology · doi:10.1097/cco.0b013e3283306647 · Cited by 40 · see citing works
Rosenstiel, P. C., Derer, S., Till, A., Häsler, R., von Eberstein, H., Bewig, B., Nikolaus, S., Nebel, A., & Schreiber, S. (2008) · Genes and Immunity · doi:10.1038/sj.gene.6364454 · Cited by 35 · see citing works
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Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · see citing works
Self-citationCellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · see citing works
Self-citationMechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · see citing works
Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines
Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00586 · Cited by 1,267 · see citing works
Palucka, A. K., & Coussens, L. M. (2016) · Cell · doi:10.1016/j.cell.2016.01.049 · Cited by 843 · see citing works
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2011.12.006 · Cited by 763 · see citing works
Astrocyte Senescence as a Component of Alzheimer’s Disease
Bhat, R., Crowe, E. P., Bitto, A., Moh, M., Katsetos, C. D., Garcia, F. U., Johnson, F. B., Trojanowski, J. Q., Sell, C., & Torres, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045069 · Cited by 586 · see citing works
Loo, T. M., Kamachi, F., Watanabe, Y., Yoshimoto, S., Kanda, H., Arai, Y., Nakajima-Takagi, Y., Iwama, A., Koga, T., Sugimoto, Y., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0932 · Cited by 478 · see citing works
Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model
Burd, C. E., Sorrentino, J. A., Clark, K. S., Darr, D. B., Krishnamurthy, J., Deal, A. M., Bardeesy, N., Castrillon, D. H., Beach, D. H., & Sharpless, N. E. (2013) · Cell · doi:10.1016/j.cell.2012.12.010 · Cited by 419 · see citing works
Ortiz-Montero, P., Londoño-Vallejo, A., & Vernot, J.-P. (2017) · Cell Communication and Signaling · doi:10.1186/s12964-017-0172-3 · Cited by 428 · see citing works
Recurrent turnover of senescent cells during regeneration of a complex structure
Yun, M. H., Davaapil, H., & Brockes, J. P. (2015) · eLife · doi:10.7554/elife.05505 · Cited by 385 · see citing works
Redox control of senescence and age-related disease.
Chandrasekaran, A., Idelchik, M. D. P. S., & Melendez, J. A. (2017) · Redox Biology · doi:10.1016/j.redox.2016.11.005 · Cited by 360 · see citing works
Hall, B. M., Balan, V., Gleiberman, A. S., Strom, E., Krasnov, P., Virtuoso, L. P., Rydkina, E., Vujcic, S., Balan, K., Gitlin, I., et al. (2016) · Aging · doi:10.18632/aging.100991 · Cited by 357 · see citing works
Pluquet, O., Pourtier, A., & Abbadie, C. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00334.2014 · Cited by 305 · see citing works
DNA damage response and metabolic disease
Shimizu, I., Yoshida, Y., Suda, M., & Minamino, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.008 · Cited by 286 · see citing works
A Senescence-Centric View of Aging: Implications for Longevity and Disease
Borghesan, M., Hoogaars, W. M. H., Varela-Eirin, M., Talma, N., & Demaria, M. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.07.002 · Cited by 267 · see citing works
Cell Senescence: Role in Aging and Age-Related Diseases
Campisi, J., & Robert, L. (2014) · Interdisciplinary Topics in Gerontology and Geriatrics · doi:10.1159/000358899 · Cited by 240 · see citing works
Self-citationBlagosklonny, M. V. (2012) · Aging · doi:10.18632/aging.100443 · Cited by 251 · see citing works
Senescent cells: SASPected drivers of age-related pathologies
Ovadya, Y., & Krizhanovsky, V. (2014) · Biogerontology · doi:10.1007/s10522-014-9529-9 · Cited by 232 · see citing works
Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies
Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., & Kirkland, J. L. (2020) · Cancers · doi:10.3390/cancers12082134 · Cited by 235 · see citing works
“It has been proposed that, whilst senescence itself is largely tumour suppressive [18], the SASP of chronically senescent cells may promote tumour recurrence or progression [19].”
BackgroundNuclear morphology is a deep learning biomarker of cellular senescence
Heckenbach, I., Mkrtchyan, G. V., Ezra, M. B., Bakula, D., Madsen, J. S., Nielsen, M. H., Oró, D., Osborne, B., Covarrubias, A. J., Idda, M. L., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00263-3 · Cited by 232 · see citing works
Philipot, D., Guérit, D., Platano, D., Chuchana, P., Olivotto, E., Espinoza, F., Dorandeu, A., Pers, Y.-M., Piette, J., Borzi, R. M., et al. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4494 · Cited by 226 · see citing works
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation
Procopio, M.-G., Laszlo, C., Al Labban, D., Kim, D. E., Bordignon, P., Jo, S.-H., Goruppi, S., Menietti, E., Ostano, P., Ala, U., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3228 · Cited by 223 · see citing works
Barascu, A., Le Chalony, C., Pennarun, G., Genet, D., Imam, N., Lopez, B., & Bertrand, P. (2012) · The EMBO Journal · doi:10.1038/emboj.2011.492 · Cited by 206 · see citing works
Lim, H., Park, H., & Kim, H. P. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.06.013 · Cited by 205 · see citing works
HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci
Aird, K. M., Iwasaki, O., Kossenkov, A. V., Tanizawa, H., Fatkhutdinov, N., Bitler, B. G., Le, L., Alicea, G., Yang, T.-L., Johnson, F. B., et al. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201608026 · Cited by 175 · see citing works
Epigenetic clock analyses of cellular senescence and ageing.
Lowe, D., Horvath, S., & Raj, K. (2016) · Oncotarget · doi:10.18632/oncotarget.7383 · Cited by 147 · see citing works
Puterman, E., Lin, J., Krauss, J., Blackburn, E. H., & Epel, E. S. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.70 · Cited by 150 · see citing works
Placental membrane aging and HMGB1 signaling associated with human parturition
Menon, R., Behnia, F., Polettini, J., Saade, G. R., Campisi, J., & Velarde, M. (2016) · Aging · doi:10.18632/aging.100891 · Cited by 143 · see citing works
Self-citationBiomarkers to identify and isolate senescent cells
Matjusaitis, M., Chin, G., Sarnoski, E. A., & Stolzing, A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.003 · Cited by 144 · see citing works
Maciel-Barón, L. A., Morales-Rosales, S. L., Aquino-Cruz, A. A., Triana-Martínez, F., Galván-Arzate, S., Luna-López, A., González-Puertos, V. Y., López-Díazguerrero, N. E., Torres, C., & Königsberg, M. (2016) · AGE · doi:10.1007/s11357-016-9886-1 · Cited by 128 · see citing works
Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019) · Nature Reviews Chemistry · doi:10.1038/s41570-019-0108-0 · Cited by 140 · see citing works
Implications of time-series gene expression profiles of replicative senescence.
Kim, Y., Byun, H., Jee, B. A., Cho, H., Seo, Y., Kim, Y., Park, M. H., Chung, H., Woo, H. G., & Yoon, G. (2013) · Aging Cell · doi:10.1111/acel.12087 · Cited by 106 · see citing works
Puterman, E., & Epel, E. (2012) · Social and Personality Psychology Compass · doi:10.1111/j.1751-9004.2012.00465.x · Cited by 106 · see citing works
Wei, Z., Chen, X.-C., Song, Y., Pan, X.-D., Dai, X.-M., Zhang, J., Cui, X.-L., Wu, X.-L., & Zhu, Y.-G. (2016) · Chinese Medical Journal · doi:10.4103/0366-6999.186646 · Cited by 89 · see citing works
Myeloid-derived suppressor cells (MDSC): an important partner in cellular/tissue senescence
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2018) · Biogerontology · doi:10.1007/s10522-018-9762-8 · Cited by 84 · see citing works
Markers of cellular senescence.
Carnero, A. (2013) · Methods in Molecular Biology · doi:10.1007/978-1-62703-239-1_4 · Cited by 68 · see citing works
Clinical perspectives on the age-related increase of immunosuppressive activity
Salminen, A. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02193-4 · Cited by 57 · see citing works
Chiappini, E., Bianconi, M., Dalzini, A., Petrara, M. R., Galli, L., Giaquinto, C., & De Rossi, A. (2018) · Aging · doi:10.18632/aging.101622 · Cited by 46 · see citing works
Senopathies-Diseases Associated with Cellular Senescence
Lushchak, O., Schosserer, M., & Grillari, J. (2023) · Biomolecules · doi:10.3390/biom13060966 · Cited by 35 · see citing works
Dynamic Metabolic Response to Adriamycin-Induced Senescence in Breast Cancer Cells
You, R., Dai, J., Zhang, P., Barding, G. A., & Raftery, D. (2018) · Metabolites · doi:10.3390/metabo8040095 · Cited by 24 · see citing works
Telomeric 8-Oxoguanine Drives Rapid Premature Senescence In The Absence Of Telomere Shortening
Barnes, R. P., de Rosa, M., Thosar, S. A., Detwiler, A. C., Roginskaya, V., Van Houten, B., Bruchez, M. P., Stewart-Ornstein, J., & Opresko, P. L. (2021) · doi:10.1101/2021.05.05.442662
- Authors
- Campisi, J., Andersen, J. K., Kapahi, P., & Melov, S.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Campisi, Judith
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 21
- Issue
- 6
- Pages
- 354-9
- ISSN
- 1044-579X (ISSN-L)
- PMC
- PMC3230665
- OpenAlex
- W1982998217
- Cited by
- 421
- References
- 90
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 21 · 2023: 22 · 2022: 28 · 2021: 35 · 2020: 29 · 2019: 28 · 2018: 29 · 2017: 32 · 2016: 43 · 2015: 32 · 2014: 45 · 2013: 29 · 2012: 22
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Cancer Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (RL1AG032113, P01AG025901, R37AG009909, R01AG018679, R01AG031337)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, senescence-associated secretory phenotype, cancer, age-related degenerative diseases, aging, tissue repair, hyperplasia, genomic damage, malignant transformation, cytokine production
- MeSH terms
- Aging, Humans, Neoplasms, Phenotype, Cellular Senescence
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