Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes
Open accessAbstract
Aging in complex multi-cellular organisms such as mammals entails distinctive changes in cells and molecules that ultimately compromise the fitness of adult organisms. These cellular and molecular changes lead to the phenotypes we recognize as aging. This review discusses some of the cellular and molecular changes that occur with age, specifically changes that occur as a result of cellular responses that evolved to ameliorate the inevitable damage that is caused by endogenous and environmental insults. Because the force of natural selection declines with age, it is likely that these processes were never optimized during their evolution to benefit old organisms. That is, some age-related changes may be the result of gene activities that were selected for their beneficial effects in young organisms, but the same gene activities may have unselected, deleterious effects in old organisms, a phenomenon termed antagonistic pleiotropy. Two cellular processes, apoptosis and cellular senescence, may be examples of antagonistic pleiotropy. Both processes are essential for the viability and fitness of young organisms, but may contribute to aging phenotypes, including certain age-related diseases.
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
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?
Normal aging is accompanied by reductions in gray matter volume and functional changes in prefrontal, medial temporal, and parietal cortices.
“magnetic resonance imaging (MRI) studies have shown that normal aging is associated with gray matter volume reductions and functional alterations in several regions critical for higher cognitive function: prefrontal, medial temporal and parietal cortices.21–24”
From Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing (2018) · cites this paper as [24]
Section 2.1 (Apoptosis; page unavailable) discusses possible neuronal loss with aging, but does not report MRI findings, gray matter volume reductions, or functional changes in the named cortices. Searches for those cortical regions and for MRI and gray matter volume found no passage addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredYoung adults may also upregulate activity in response to increased task demands, but the demand threshold for upregulation may be higher in young than in older adults.
“It is worth noting that young adults may also upregulate activity in response to increased task demands, but that the demand threshold for upregulation may be higher in young, compared to older adults24,36.”
From Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing (2018) · cites this paper as [24]
Section 2.1 discusses apoptosis and neuronal compensation after cell loss; Figure 1 discusses thresholds at which tissue health becomes compromised. Neither addresses activity upregulation in response to task demands or compares the demand thresholds of young and older adults (searched for task demands and cognitive activity upregulation). Page numbers are unavailable in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
Apoptosis in the Pathogenesis and Treatment of Disease
Thompson, C. B. (1995) · Science · doi:10.1126/science.7878464 · Cited by 6,524 · see citing works
Extension 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 · see citing works
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649 · see citing works
Mechanisms and Functions of Cell Death
Ellis, R. E., Yuan, J., & Horvitz, H. R. (1991) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.07.110191.003311 · Cited by 2,063 · see citing works
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051 · see citing works
Kirkwood, 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-citationVaux, D. L., & Korsmeyer, S. J. (1999) · Cell · doi:10.1016/s0092-8674(00)80564-4 · Cited by 1,564 · see citing works
p53 mutant mice that display early ageing-associated phenotypes
Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., et al. (2002) · Nature · doi:10.1038/415045a · Cited by 1,459 · cited 1× · see citing works
“Strikingly, it also accelerated aging in some tissues, and modestly decreased the life span (Tyner et al., 2002).”
BackgroundTelomere states and cell fates
Blackburn, E. H. (2000) · Nature · doi:10.1038/35040500 · Cited by 1,372 · see citing works
Apoptosis: Mechanisms and Roles in Pathology
Arends, M. J., & Wyllie, A. H. (1991) · International review of experimental pathology · doi:10.1016/b978-0-12-364932-4.50010-1 · Cited by 1,334 · see citing works
Handbook of the Biology of Aging
Finch, C. E., & Schneider, E. L. (1990) · DigitalGeorgetown (Georgetown University Library) · Cited by 1,210 · see citing works
Apoptosis And Programmed Cell Death In Immunity
Cohen, J., Duke, R. C., Fadok, V. A., & Sellins, K. S. (1992) · Annual Review of Immunology · doi:10.1146/annurev.iy.10.040192.001411 · Cited by 1,112 · see citing works
Telomere end-replication problem and cell aging
Levy, M. Z., Allsopp, R. C., Futcher, A. B., Greider, C. W., & Harley, C. B. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90096-3 · Cited by 1,069 · see citing works
Meier, P., Finch, A. J., & Evan, G. I. (2000) · Nature · doi:10.1038/35037734 · Cited by 1,027 · see citing works
Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations
Weissman, I. L., Anderson, D. J., & Gage, F. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.387 · Cited by 948 · 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-citationSherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745 · see citing works
Telomere length and replicative aging in human vascular tissues.
Chang, E., & Harley, C. B. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11190 · Cited by 635 · see citing works
Replicative Senescence: Implications for in Vivo Aging and Tumor Suppression
Smith, J. R., & Pereira-Smith, O. M. (1996) · Science · doi:10.1126/science.273.5271.63 · Cited by 547 · see citing works
(1993) · PubMed · Cited by 469 · see citing works
Identification and behavior of epithelial stem cells in the Drosophila ovary
Margolis, J. S., & Spradling, A. C. (1995) · Development · doi:10.1242/dev.121.11.3797 · Cited by 448 · see citing works
Replicative Senescence: An Old Lives' Tale?
Campisi, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81023-5 · Cited by 434 · see citing works
Self-citationRoles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress
Amundson, S. A., Myers, T. G., & Fornace, A. J. (1998) · Oncogene · doi:10.1038/sj.onc.1202576 · Cited by 424 · 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
Cellular senescence, cancer and aging: the telomere connection
Campisi, J., Kim, S.-H., Lim, C.-S., & Rubio, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00160-7 · Cited by 400 · see citing works
Self-citationTumor suppressors and oncogenes in cellular senescence
Bringold, F., & Serrano, M. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00083-8 · Cited by 379 · see citing works
(2000) · PubMed · Cited by 371 · see citing works
Self-citationMechanisms of apoptosis avoidance in cancer
Reed, J. C. (1999) · Current Opinion in Oncology · doi:10.1097/00001622-199901000-00014 · Cited by 371 · see citing works
Regulation 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-citationJazwinski, S. M. (1996) · Science · doi:10.1126/science.273.5271.54 · Cited by 354 · see citing works
Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas
Paradis, V., Youssef, N., Dargère, D., Bâ, N., Bonvoust, F., Deschatrette, J., & Bedossa, P. (2001) · Human Pathology · doi:10.1053/hupa.2001.22747 · Cited by 314 · see citing works
Replicative senescence of human fibroblast-like cells in culture
Cristofalo, V. J., & Pignolo, R. J. (1993) · Physiological Reviews · doi:10.1152/physrev.1993.73.3.617 · Cited by 286 · see citing works
Necrotic and apoptotic myocyte cell death in the aging heart of Fischer 344 rats
Kajstura, J., Cheng, W. N., Ranganathan, S., Li, P., Li, B., Nitahara, J., Chapnick, S., Krzysztof Reiss, F., Olivetti, G., & Anversa, P. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.271.3.h1215 · Cited by 272 · see citing works
Grasl‐Kraupp, B., Bursch, W., Ruttkay-Nedecký, B., Wagner, A. E., Lauer, B., & Schulte‐Hermann, R. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9995 · Cited by 268 · see citing works
From cells to organisms: can we learn about aging from cells in culture?
Campisi, J. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00230-8 · Cited by 263 · see citing works
Self-citationAging and Cancer: The Double‐Edged Sword of Replicative Senescence
Campisi, J. (1997) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1997.tb05175.x · Cited by 254 · see citing works
Self-citationApoptosis in Human Disease: A New Skin for the Old Ceremony?
Fadeel, B., Orrenius, S., & Zhivotovsky, B. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1888 · Cited by 249 · see citing works
VASILE, E., TOMITA, Y., BROWN, L. F., KOCHER, O., & DVORAK, H. F. (2001) · The FASEB Journal · doi:10.1096/fj.00-0051com · Cited by 232 · see citing works
Replicative Senescence and Cell Immortality: The Role of Telomeres and Telomerase
Chiu, C. P., & Harley, C. B. (1997) · Experimental Biology and Medicine · doi:10.3181/00379727-214-44075 · Cited by 214 · see citing works
Senescence as a mode of tumor suppression.
Sager, R. (1991) · Environmental Health Perspectives · doi:10.1289/ehp.919359 · Cited by 213 · see citing works
Sedivy, J. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9078 · Cited by 182 · see citing works
Zhang, Y., & Herman, B. A. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00349-9 · Cited by 178 · see citing works
Seluanov, A., Gorbunova, V., Falcovitz, A., Sigal, A., Milyavsky, M., Zurer, I., Shohat, G., Goldfinger, N., & Rotter, V. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.5.1552-1564.2001 · Cited by 178 · see citing works
Choi, J. J., Shendrik, I., Peacocke, M., Peehl, D. M., Buttyan, R. E., Ikeguchi, E. F., Katz, A. E., & Benson, M. C. (2000) · Urology · doi:10.1016/s0090-4295(00)00538-0 · Cited by 173 · see citing works
Kaelin, W. G. (1999) · Oncogene · doi:10.1038/sj.onc.1202955 · Cited by 172 · see citing works
Deciphering the pathways of life and death
Li, H., & Yuan, J. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80035-0 · Cited by 171 · see citing works
Genotoxic and non-genotoxic pathways of p53 induction
Pluquet, O., & Hainaut, P. L. (2001) · Cancer Letters · doi:10.1016/s0304-3835(01)00698-x · Cited by 170 · see citing works
Aging Enhances the Activation of the Permeability Transition Pore in Mitochondria
Mather, M. W., & Rottenberg, H. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2994 · Cited by 134 · see citing works
Telomeres and Telomerase: Implications for Cancer and Aging
Shay, J. W., & Wright, W. E. (2001) · Radiation Research · doi:10.1667/0033-7587(2001)155[0188:tatifc]2.0.co;2 · Cited by 134 · see citing works
Jennings, B. J., Ozanne, S. E., & Hales, C. N. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3077 · Cited by 126 · see citing works
Aging alters the apoptotic response to genotoxic stress
Suh, Y., Lee, K.-A., Kim, W. H., Han, B. G., Vijg, J., & Park, S. C. (2002) · Nature Medicine · doi:10.1038/nm0102-3 · Cited by 114 · see citing works
Ding, G., Franki, N., Kapasi, A. A., Reddy, K., Gibbons, N., & Singhal, P. C. (2001) · Experimental and Molecular Pathology · doi:10.1006/exmp.2000.2346 · Cited by 103 · see citing works
Mouse models in tumor suppression
Ghebranious, N., & Donehower, L. A. (1998) · Oncogene · doi:10.1038/sj.onc.1202573 · Cited by 103 · see citing works
Replicative Senescence and Cell Death
Linskens, M. H. K., Harley, C. B., West, M. D., Campisi, J., & Hayflick, L. (1995) · Science · doi:10.1126/science.7848496 · Cited by 93 · see citing works
Self-citationFunctional Decline in Aging and Disease: A Role for Apoptosis
Joaquin, A. M., & Gollapudi, S. V. S. (2001) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2001.04990.x · Cited by 89 · see citing works
Muskhelishvili, L., Hart, R. W., Turturro, A., & James, S. J. (1995) · Europe PMC (PubMed Central) · Cited by 85 · see citing works
Hormonal regulation of physiological cell turnover and apoptosis
Medh, R. D., & Thompson, E. B. (2000) · Cell and Tissue Research · doi:10.1007/s004419900159 · Cited by 83 · see citing works
Control of fibroblast senescence and activation of programmed cell death
Wang, E., Lee, M., & Pandey, S. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240540410 · Cited by 78 · see citing works
Replicative senescence: Considerations relating to the stability of heterochromatin domains
Howard, B. H. (1996) · Experimental Gerontology · doi:10.1016/0531-5565(95)00022-4 · Cited by 74 · see citing works
Mouse models for multistep tumorigenesis.
Wu, X.-M., & Pandolfi, P. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)02127-4 · Cited by 70 · see citing works
Higami, Y., Shimokawa, I., Tomita, M., Okimoto, T., Koji, T., Kobayashi, N., & Ikeda, T. (1997) · Europe PMC (PubMed Central) · Cited by 56 · see citing works
Animal Models of Tumor-Suppressor Genes
Hakem, R., & Mak, T. W. (2001) · Annual Review of Genetics · doi:10.1146/annurev.genet.35.102401.090432 · Cited by 55 · see citing works
The Role of Telomerase Expression and Telomere Length Maintenance in Human and Mouse
Nan-PIng, W., & Hodes, R. J. (2000) · Journal of Clinical Immunology · doi:10.1023/a:1017223602293 · Cited by 49 · see citing works
Adult Stem Cell Plasticity and Methods of Detection
Almeida-Porada, G. D., Porada, C. D., & Zanjani, E. D. (2001) · Reviews in Clinical and Experimental Hematology · doi:10.1046/j.1468-0734.2001.00027.x · Cited by 47 · see citing works
p53 Variants Predisposing to Cancer Are Present in Healthy Centenarians
Bonafè, M., Olivieri, F., Mari, D., Baggio, G., Mattace, R., Sansoni, P., Benedictis, G. D., Luca, M. D., Bertolini, S., Barbi, C., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302196 · Cited by 42 · see citing works
Imai, K., & Senoo, H. (1998) · The Anatomical Record · doi:10.1002/(sici)1097-0185(199804)250:4 · Cited by 34 · see citing works
Leung, J. K., & Pereira‐Smith, O. M. (2001) · Novartis Foundation symposium · doi:10.1002/0470868694.ch10 · Cited by 15 · see citing works
Allen (1999) · doi:10.1002/(sici)1097-4652(199907)180:1
Flagged first, then by citations
Research works printed but not linked: 1
- Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O. M., Peacocke, M., Campisi, J. 1995. A novel biomarker identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. USA 92, 9363-9367.
Cited by
Sorted by citations
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-citationCellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277 · see citing works
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., & Sinclair, D. A. (2004) · Science · doi:10.1126/science.1099196 · Cited by 1,924 · see citing works
Walston, J., Hadley, E. C., Ferrucci, L., Guralnik, J. M., Newman, A. B., Studenski, S. A., Ershler, W. B., Harris, T., & Fried, L. P. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00745.x · Cited by 1,605 · see citing works
Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing
Cabeza, R., Albert, M., Belleville, S., Craik, F. I. M., Duarte, A., Grady, C. L., Lindenberger, U., Nyberg, L., Park, D. C., Reuter-Lorenz, P. A., et al. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0068-2 · Cited by 1,289 · 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
Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival
Yang, H., Yang, T., Baur, J. A., Perez, E., Matsui, T., Carmona, J. J., Lamming, D. W., Souza-Pinto, N. C., Bohr, V. A., Rosenzweig, A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.035 · Cited by 950 · see citing works
TGF-β1 Signaling and Tissue Fibrosis
Kim, K. K., Sheppard, D., & Chapman, H. A. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022293 · Cited by 800 · see citing works
DNA damage response and cellular senescence in tissues of aging mice
Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696 · see citing works
Cardiac Stem Cell and Myocyte Aging, Heart Failure, and Insulin-Like Growth Factor-1 Overexpression
Torella, D., Rota, M., Nurzyńska, D., Musso, E., Monsen, A., Shiraishi, I., Zias, E. A., Walsh, K., Rosenzweig, A., Sussman, M. A., et al. (2004) · Circulation Research · doi:10.1161/01.res.0000117306.10142.50 · Cited by 538 · see citing works
When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly
Turnheim, K. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00133-5 · Cited by 531 · see citing works
Rajah, M. N., & D'Esposito, M. (2005) · Brain · doi:10.1093/brain/awh608 · Cited by 513 · see citing works
p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes
Davalos, A. R., Kawahara, M., Malhotra, G. K., Schaum, N., Huang, J., Ved, U., Beausejour, C. M., Coppe, J.-P., Rodier, F., & Campisi, J. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201206006 · Cited by 439 · see citing works
Self-citationCD28 extinction in human T cells: altered functions and the program of T‐cell senescence
Vallejo, A. N. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00256.x · Cited by 435 · see citing works
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 · see citing works
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 · see citing works
Mechanisms of cellular senescence in human and mouse cells.
Itahana, K., Campisi, J., & Dimri, G. P. (2004) · Biogerontology · doi:10.1023/b:bgen.0000017682.96395.10 · Cited by 338 · see citing works
Self-citationThe Biology of Aging and Frailty
Fedarko, N. S. (2010) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.08.006 · Cited by 344 · see citing works
From Bedside to Bench: Research Agenda for Frailty
Fried, L. P., Hadley, E. C., Walston, J. D., Newman, A. B., Guralnik, J. M., Studenski, S. A., Harris, T. B., Ershler, W. B., & Ferrucci, L. (2005) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2005.31.pe24 · Cited by 299 · see citing works
Cellular senescence and the aging brain
Chinta, S. J., Woods, G., Rane, A., Demaria, M., Campisi, J., & Andersen, J. K. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.09.018 · Cited by 282 · see citing works
Self-citationReplicative 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 275 · see citing works
Oxidative Stress Damage as a Detrimental Factor in Preterm Birth Pathology
Menon, R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00567 · Cited by 249 · see citing works
Life history trade-offs in cancer evolution
Aktipis, A., Boddy, A. M., Gatenby, R. A., Brown, J. S., & Maley, C. C. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3606 · Cited by 236 · see citing works
Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.01.002 · Cited by 223 · see citing works
Telomere length and dynamics predict mortality in a wild longitudinal study
Barrett, E. L. B., Burke, T. A., Hammers, M., Komdeur, J., & Richardson, D. S. (2012) · Molecular Ecology · doi:10.1111/mec.12110 · Cited by 217 · see citing works
Cellular responses to reactive oxygen species-induced DNA damage and aging
Bertram, C., & Hass, R. (2008) · Biological Chemistry · doi:10.1515/bc.2008.031 · Cited by 208 · see citing works
SIRT1 regulation of apoptosis of human chondrocytes
Takayama, K., Ishida, K., Matsushita, T., Fujita, N., Hayashi, S., Sasaki, K., Tei, K., Kubo, S., Matsumoto, T., Fujioka, H., et al. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24864 · Cited by 207 · see citing works
The impact of cerebrovascular aging on vascular cognitive impairment and dementia
Yang, T., Sun, Y., Lu, Z., Leak, R. K., & Zhang, F. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.007 · Cited by 206 · see citing works
The Immune System in the Elderly: Activation-Induced and Damage-Induced Apoptosis
Ginaldi, L., Martinis, M. D., Monti, D., & Franceschi, C. (2004) · Immunologic Research · doi:10.1385/ir:30:1:081 · Cited by 202 · see citing works
Menon, R., Boldogh, I. R., Hawkins, H. K., Woodson, M., Polettini, J., Syed, T. A., Fortunato, S. J., Saade, G. R., Papaconstantinou, J., & Taylor, R. N. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.02.011 · Cited by 196 · see citing works
Telomeres: Linking stress and survival, ecology and evolution
Haussmann, M. F., & Marchetto, N. M. (2010) · Current Zoology · doi:10.1093/czoolo/56.6.714 · Cited by 193 · see citing works
Knudson, C. B., & Knudson, W. (2004) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000143804.26638.82 · Cited by 180 · see citing works
Aging, tumor suppression and cancer: high wire-act!
Campisi, J. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.09.024 · Cited by 171 · see citing works
Self-citationTelomere Attrition Due to Infection
Ilmonen, P., Kotrschal, A., & Penn, D. J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002143 · Cited by 170 · see citing works
Tamori, Y., & Deng, W. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.04.013 · Cited by 154 · see citing works
Quirici, V., Guerrero, C. J., Krause, J. S., Wingfield, J. C., & Vásquez, R. A. (2016) · Frontiers in Zoology · doi:10.1186/s12983-016-0133-5 · Cited by 145 · see citing works
Chien, K. R., & Karsenty, G. (2005) · Cell · doi:10.1016/j.cell.2005.02.006 · Cited by 142 · see citing works
Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress
Sanders, Y. Y., Liu, H., Zhang, X., Hecker, L., Bernard, K., Desai, L., Liu, G., & Thannickal, V. J. (2013) · Redox Biology · doi:10.1016/j.redox.2012.11.004 · Cited by 138 · see citing works
Martin-Ruiz, C. M., Saretzki, G. C., Petrie, J., Ladhoff, J., Jeyapalan, J. C., Wei, W., Sedivy, J. M., & von Zglinicki, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311980200 · Cited by 135 · see citing works
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 · see citing works
Self-citationOvarian cancer: pathology, biology, and disease models
Daniel, G. R. (2009) · Frontiers in bioscience · doi:10.2741/3364 · Cited by 131 · see citing works
LEARNING ABILITY AND LONGEVITY: A SYMMETRICAL EVOLUTIONARY TRADE-OFF IN DROSOPHILA
Burger, J. M. S., Kolß, M., Pont, J., & Kawecki, T. J. (2008) · Evolution · doi:10.1111/j.1558-5646.2008.00376.x · Cited by 126 · see citing works
Biological, Clinical, and Psychosocial Correlates at the Interface of Cancer and Aging Research
Dale, W., Mohile, S. G., Eldadah, B. A., Trimble, E. L., Schilsky, R. L., Cohen, H. J., Muss, H. B., Schmader, K. E., FERRELL, B. R., Extermann, M., et al. (2012) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djs145 · Cited by 114 · see citing works
Anisimov, V. N. (2007) · Cancer Control · doi:10.1177/107327480701400104 · Cited by 108 · see citing works
Expression of SUMO-2/3 Induced Senescence through p53- and pRB-mediated Pathways
Li, T., Santockyte, R., Shen, R., Tekle, E., Wang, G., Yang, D. C. H., & Chock, P. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608236200 · Cited by 107 · 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
de Magalhães, J. P. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.07.006 · Cited by 106 · see citing works
Molecular mechanisms of cardiomyocyte aging
Sheydina, A., Riordon, D. R., & Boheler, K. R. (2011) · Clinical Science · doi:10.1042/cs20110115 · Cited by 101 · see citing works
Differential patterns of apoptosis in response to aging in <i>Drosophila</i>
Zheng, J., Edelman, S. W., Tharmarajah, G., Walker, D. W., Pletcher, S. D., & Seroude, L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503374102 · Cited by 100 · see citing works
Male age, germline mutations and the benefits of polyandry
Radwan, J. (2003) · Ecology Letters · doi:10.1046/j.1461-0248.2003.00484.x · Cited by 99 · see citing works
Proteasome inhibition by chronic oxidative stress in human trabecular meshwork cells
Caballero, M., Liton, P. B., Epstein, D. L., & González, P. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01385-8 · Cited by 98 · see citing works
Wu, L. W., Wang, Y.-L., Christensen, J. M., Khalifian, S., Schneeberger, S., Raimondi, G., Cooney, D. S., Lee, W. P. A., & Brandacher, G. (2014) · Transplant Immunology · doi:10.1016/j.trim.2014.03.001 · Cited by 94 · see citing works
Spatio‐temporal variation in lifelong telomere dynamics in a long‐term ecological study
Spurgin, L. G., Bebbington, K., Fairfield, E. A., Hammers, M., Komdeur, J., Burke, T. A., Dugdale, H. L., & Richardson, D. S. (2017) · Journal of Animal Ecology · doi:10.1111/1365-2656.12741 · Cited by 92 · see citing works
Iron Accumulation During Cellular Senescence in Human Fibroblasts <i>In Vitro</i>
Killilea, D. W., Atamna, H., Liao, C., & Ames, B. N. (2003) · Antioxidants & Redox Signaling · doi:10.1089/152308603770310158 · Cited by 92 · see citing works
Comparative aspects of zebrafish (Danio rerio) as a model for aging research
Gerhard, G. S. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.10.022 · Cited by 89 · see citing works
Analysis of age-related changes in the functional morphologies of salivary glands in mice
Choi, J., Park, I. S., Kim, S.-K., Lim, J., & Kim, Y. (2013) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2013.07.008 · Cited by 83 · see citing works
Correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference
Huang, S., Chen, L., Libina, N., Janes, J. H., Martin, G. M., Campisi, J., & Oshima, J. (2005) · Human Genetics · doi:10.1007/s00439-005-0051-7 · Cited by 82 · see citing works
Self-citationManagement of multicellular senescence and oxidative stress
Haines, D. D., Juhász, B., & Tósaki, Á. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12074 · Cited by 80 · see citing works
Pearce, D. J., Anjos‐Afonso, F., Ridler, C. M., Eddaoudi, A., & Bonnet, D. A. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0405 · Cited by 77 · see citing works
Ravelojaona, V., Robert, A. M., & Robert, L. (2008) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2007.12.004 · Cited by 73 · see citing works
Relationships between cancer and aging: a multilevel approach
Anisimov, V. N., Sikora, E., & Pawelec, G. (2009) · Biogerontology · doi:10.1007/s10522-008-9209-8 · Cited by 70 · see citing works
Replicative senescence and the art of counting
von Zglinicki, T. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.09.015 · Cited by 68 · see citing works
Chronic antigenic load and apoptosis in immunosenescence
Ginaldi, L., Martinis, M. D., Monti, D., & Franceschi, C. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.11.005 · Cited by 65 · see citing works
Exterkate, L., Slegtenhorst, B. R., Kelm, M., Seyda, M., Schuitenmaker, J. M., Quante, M., Uehara, H., Elkhal, A., & Tullius, S. G. (2015) · Transplantation · doi:10.1097/tp.0000000000001003 · Cited by 63 · see citing works
Adipose tissue, immune aging, and cellular senescence
Frasca, D., & Blomberg, B. B. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00812-1 · Cited by 66 · see citing works
Liu, M., Gu, L., Zhang, Y., Li, Y., Zhang, L., Xin, Y., Wang, Y., & Xu, Z. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217025 · Cited by 57 · see citing works
Balancing DNA repair to prevent ageing and cancer
Stead, E. R., & Bjedov, I. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112679 · Cited by 56 · see citing works
Identification of evolutionarily conserved genetic regulators of cellular aging
Laschober, G. T., Ruli, D., Hofer, E., Mück, C., Carmona‐Gutiérrez, D., Ring, J., Hütter, E., Ruckenstuhl, C., Mičutková, L., Brunauer, R., et al. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00637.x · Cited by 54 · see citing works
Bullón, P., Battino, M. A., Varela‐López, A., Pérez-López, P., Granados-Principal, S. M., Ramírez-Tortosa, M. C., Ochoa, J. J., Cordero, M. D., González-Alonso, A., Ramírez-Tortosa, C. L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074234 · Cited by 54 · see citing works
A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models
Zhao, Y., Wu, L., Yue, X., Zhang, C., Wang, J., Li, J., Sun, X., Zhu, Y., Feng, Z., & Hu, W. (2018) · eLife · doi:10.7554/elife.34701 · Cited by 53 · see citing works
Increased Arf/p53 activity in stem cells, aging and cancer
Carrasco‐García, E., Moreno, M., Moreno‐Cugnon, L., & Matheu, A. (2017) · Aging Cell · doi:10.1111/acel.12574 · Cited by 51 · see citing works
Signaling pathway requirements for induction of senescence by telomere homolog oligonucleotides
Li, G., Eller, M. S., Hanna, K., & Gilchrest, B. A. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.08.019 · Cited by 49 · see citing works
Mather, K. A., Jorm, A. F., Milburn, P. J., Tan, X., Easteal, S., & Christensen, H. M. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq050 · Cited by 48 · see citing works
Kajstura, J., Bolli, R., Sonnenblick, E. H., Anversa, P., & Leri, A. (2006) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2005.12.013 · Cited by 48 · see citing works
Moh, M. C., Zhang, T., Lee, L. H., & Shen, S. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn226 · Cited by 47 · see citing works
Age dependence of male mating ability and sperm competition success in the bulb mite
Radwan, J., Michalczyk, Ł., & Prokop, Z. M. (2005) · Animal Behaviour · doi:10.1016/j.anbehav.2004.09.006 · Cited by 47 · see citing works
Frasca, D., Romero, M., Diaz, A., Garcia, D., Thaller, S. R., & Blomberg, B. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041839 · Cited by 43 · see citing works
Nikitakis, N. G., Sauk, J. J., & Papanicolaou, S. I. (2004) · Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology · doi:10.1016/j.tripleo.2003.12.032 · Cited by 42 · see citing works
Aging stem cells, latexin, and longevity
Liang, Y., & Zant, G. E. V. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.032 · Cited by 42 · see citing works
Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice
Kim, J., Vaish, V., Feng, M., Field, K., Chatzistamou, I., & Shim, M. (2016) · Aging · doi:10.18632/aging.101060 · Cited by 41 · see citing works
Atamna, H., Atamna, W., Al-Eyd, G., Shanower, G., & Dhahbi, J. M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.09.004 · Cited by 40 · see citing works
Senescent cells at the crossroads of aging, disease, and tissue homeostasis
Kuehnemann, C., & Wiley, C. D. (2023) · Aging Cell · doi:10.1111/acel.13988 · Cited by 41 · see citing works
New Insights on Molecular Mechanisms of Renal Aging
Schmitt, R., & Melk, A. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04214.x · Cited by 39 · see citing works
Genomic regulation of senescence and innate immunity signaling in the retinal pigment epithelium
Chaum, E., Winborn, C. S., & Bhattacharya, S. (2015) · Mammalian Genome · doi:10.1007/s00335-015-9568-9 · Cited by 40 · see citing works
Aging, Senescence, and Human Variation
Crews, D. E., & Ice, G. H. (2012) · Human Biology · doi:10.1002/9781118108062.ch13 · Cited by 39 · see citing works
miR-290 acts as a physiological effector of senescence in mouse embryo fibroblasts
Pitto, L., Rizzo, M., Simili, M., Colligiani, D., Evangelista, M., Mercatanti, A., Mariani, L., Cremisi, F., & Rainaldi, G. (2009) · Physiological Genomics · doi:10.1152/physiolgenomics.00085.2009 · Cited by 38 · see citing works
Increased ROS generation in subsets of OGG1 knockout fibroblast cells
Bácsi, A., Chodaczek, G., Hazra, T. K., Konkel, D. A., & Boldogh, I. R. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.09.005 · Cited by 38 · see citing works
Causes and consequences of telomere lengthening in a wild vertebrate population
Brown, T. J., Spurgin, L. G., Dugdale, H. L., Komdeur, J., Burke, T. A., & Richardson, D. S. (2021) · Molecular Ecology · doi:10.1111/mec.16059 · Cited by 37 · see citing works
Boehm, A. K., Seth, M., Mayr, K. G., & Fortier, L. A. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22664 · Cited by 37 · see citing works
Aging and the programmed death phenomena
Skulachev, V. P. (2003) · Topics in current genetics · doi:10.1007/978-3-540-37005-5_8 · Cited by 36 · see citing works
Histone demethylase JMJD3 at the intersection of cellular senescence and cancer
Perrigue, P. M., Najbauer, J., & Barciszewski, J. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.03.002 · Cited by 33 · see citing works
Wang, F., Deng, A., Li, M., Wei, J., Qin, H., & Wang, A. (2012) · Molecules · doi:10.3390/molecules18010418 · Cited by 33 · see citing works
Wang, X., Brégégère, F. M., Soroka, Y., Frušić‐Zlotkin, M., & Milner, Y. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.04.083 · Cited by 33 · see citing works
Li, L.-H., Wu, L.-J., Tashiro, S., Onodera, S., Uchiumi, F., & Ikejima, T. (2007) · Journal of Asian Natural Products Research · doi:10.1080/10286020600604260 · Cited by 31 · see citing works
Targeting DNA damage in ageing: towards supercharging DNA repair
Bujarrabal-Dueso, A., Garinis, G. A., Robbins, P. D., Vijg, J., & Schumacher, B. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01212-6 · Cited by 30 · see citing works
Involvement of IL‐1 family proteins in p38 linked cellular senescence of mouse embryonic fibroblasts
Uekawa, N., Nishikimi, A., Isobe, K.-I., Iwakura, Y., & Maruyama, M. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.08.033 · Cited by 29 · see citing works
Telomere dynamics in the first year of life, but not later in life, predict lifespan in a wild bird
Sheldon, E. L., Eastwood, J. R., Teunissen, N., Roast, M. J., Aranzamendi, N. H., Fan, M., Hall, M. L., Kingma, S. A., Verhulst, S., & Peters, A. (2021) · Molecular Ecology · doi:10.1111/mec.16296 · Cited by 26 · see citing works
Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes
Tejada-Martinez, D., Avelar, R., de Magalhães, J. D., Lopes, I., Zhang, B., Novoa, G., & Trizzino, M. (2021) · bioRxiv · doi:10.1093/molbev/msab369 · Cited by 22 · see citing works
Analysis of Cellular Senescence in Culture In Vivo: The Senescence‐Associated β‐Galactosidase Assay
Bandyopadhyay, D., Gatza, C. E., Donehower, L. A., & Medrano, E. E. (2005) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb1809s27 · Cited by 27 · see citing works
Enoki, N., Kiyoshima, T., Sakai, T., Kobayashi, I., Takahashi, K., Terada, Y., & Sakai, H. (2007) · Journal of Molecular Histology · doi:10.1007/s10735-007-9105-6 · Cited by 27 · see citing works
- Authors
- Campisi, J.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Campisi, J
- ORCID
- Campisi, J
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 38
- Issue
- 1-2
- Pages
- 5-11
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W1973723400
- Cited by
- 218
- References
- 70
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 6 · 2019: 2 · 2018: 8 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 10 · 2013: 11 · 2012: 11
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.escholarship.org
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Energy
- Ellison Medical Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- cellular senescence, apoptosis, aging, antagonistic pleiotropy, age-related diseases, natural selection, evolutionary trade-offs, aging phenotypes
- MeSH terms
- Aged, Aging, Animals, Gene Expression Regulation, Humans, Mammals, Neoplasms, Genes, Tumor Suppressor, Cellular Senescence, Apoptosis, Multifactorial Inheritance
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
