The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
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.
Citations
Cites
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Apoptosis in the Pathogenesis and Treatment of Disease
Thompson, C. B. (1995) · Science · doi:10.1126/science.7878464 · Cited by 6,524
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
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
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 2,088
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
Kirkwood, T. B. L., & Austad, S. N. (2000) · Nature · doi:10.1038/35041682 · Cited by 1,774
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
Self-citationVaux, D. L., & Korsmeyer, S. J. (1999) · Cell · doi:10.1016/s0092-8674(00)80564-4 · Cited by 1,564
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×
“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 1,395
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
Handbook of the Biology of Aging
Finch, C. E., & Schneider, E. L. (1990) · DigitalGeorgetown (Georgetown University Library) · Cited by 1,210
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
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
Meier, P., Finch, A. J., & Evan, G. I. (2000) · Nature · doi:10.1038/35037734 · Cited by 1,027
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
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745
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 642
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
(1993) · PubMed · Cited by 469
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
Replicative Senescence: An Old Lives' Tale?
Campisi, J. (1996) · Cell · doi:10.1016/s0092-8674(00)81023-5 · Cited by 437
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
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
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
Self-citationCellular senescence as a tumor-suppressor mechanism
Campisi, J. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)82148-6 · Cited by 390
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
Mechanisms of apoptosis avoidance in cancer
Reed, J. C. (1999) · Current Opinion in Oncology · doi:10.1097/00001622-199901000-00014 · Cited by 377
(2000) · PubMed · Cited by 371
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
Self-citationJazwinski, S. M. (1996) · Science · doi:10.1126/science.273.5271.54 · Cited by 356
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
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
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
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
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 267
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
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 253
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
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
Senescence as a mode of tumor suppression.
Sager, R. (1991) · Environmental Health Perspectives · doi:10.1289/ehp.919359 · Cited by 213
Sedivy, J. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9078 · Cited by 182
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 182
Zhang, Y., & Herman, B. A. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00349-9 · Cited by 178
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
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 177
Kaelin, W. G. (1999) · Oncogene · doi:10.1038/sj.onc.1202955 · Cited by 172
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
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
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
Jennings, B. J., Ozanne, S. E., & Hales, C. N. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3077 · Cited by 129
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 115
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
Mouse models in tumor suppression
Ghebranious, N., & Donehower, L. A. (1998) · Oncogene · doi:10.1038/sj.onc.1202573 · Cited by 103
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
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 90
Muskhelishvili, L., Hart, R. W., Turturro, A., & James, S. J. (1995) · Europe PMC (PubMed Central) · Cited by 85
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 85
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
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
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
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 57
Higami, Y., Shimokawa, I., Tomita, M., Okimoto, T., Koji, T., Kobayashi, N., & Ikeda, T. (1997) · Europe PMC (PubMed Central) · Cited by 56
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
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
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
Imai, K., & Senoo, H. (1998) · The Anatomical Record · doi:10.1002/(sici)1097-0185(199804)250:4 · Cited by 34
Leung, J. K., & Pereira‐Smith, O. M. (2001) · Novartis Foundation symposium · doi:10.1002/0470868694.ch10 · Cited by 15
Allen (1999) · doi:10.1002/(sici)1097-4652(199907)180:1
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 2,379
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
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
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
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 1,298
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
