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Cellular Senescence and the Biology of Aging, Disease, and Frailty
Open accessAbstract
Population aging simultaneously highlights the remarkable advances in science, medicine, and public policy, and the formidable challenges facing society. Indeed, aging is the primary risk factor for many of the most common chronic diseases and frailty, which result in profound social and economic costs. Population aging also reveals an opportunity, i.e. interventions to disrupt the fundamental biology of aging could significantly delay the onset of age-related conditions as a group, and, as a result, extend the healthy life span, or health span. There is now considerable evidence that cellular senescence is an underlying mechanism of aging and age-related conditions. Cellular senescence is a process in which cells lose the ability to divide and damage neighboring cells by the factors they secrete, collectively referred to as the senescence-associated secretory phenotype (SASP). Herein, we discuss the concept of cellular senescence, review the evidence that implicates cellular senescence and SASP in age-related deterioration, hyperproliferation, and inflammation, and propose that this underlying mechanism of aging may play a fundamental role in the biology of frailty.
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“The use of senotherapeutic drugs could potentially be effective in treating a variety of conditions primarily or secondarily mediated by accumulation of senescent cells [6, 33, 67–87].”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [72]
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Frailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Self-citationThe Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584
Self-citationA complex secretory program orchestrated by the inflammasome controls paracrine senescence
Acosta, J. C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J. P., Athineos, D., Kang, T.-W., Lasitschka, F., Andrulis, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2784 · Cited by 2,278
Frailty as a predictor of surgical outcomes in older patients
Makary, M. A., Segev, D. L., Pronovost, P. J., Syin, D., Bandeen-Roche, K., Patel, P., Takenaga, R., Devgan, L., Holzmueller, C. G., Tian, J., et al. (2010) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2010.01.028 · Cited by 2,184
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,070
Cellular 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
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Items 101–148 of 148
Marchante, M., Ramírez-Martín, N., Buigues, A., Martínez, J., Pellicer, N., Pellicer, A., & Herraiz, S. (2023) · Aging · doi:10.18632/aging.205086 · Cited by 14
Mielke, M. M., Fielding, R. A., Atkinson, E. J., Aversa, Z., Schafer, M. J., Cummings, S. R., Pahor, M., Leeuwenburgh, C., & LeBrasseur, N. K. (2025) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2025.100529 · Cited by 13
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Brauer, L., Krüger, K., Weyh, C., & Alack, K. (2021) · Immuno · doi:10.3390/immuno1030009 · Cited by 11
Pharmacologic Interventions for Fracture Risk Reduction in the Oldest Old: What Is the Evidence?
Sfeir, J. G., & Pignolo, R. J. (2021) · JBMR Plus · doi:10.1002/jbm4.10538 · Cited by 11
Forsyth, C. B., Shaikh, M. W., Engen, P. A., Preuss, F., Naqib, A. D., Palmen, B. A., Green, S. J., Zhang, L., Bogin, Z. R., Lawrence, K. M., et al. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1352299 · Cited by 11
p16High immune cells control disease tolerance as a defense and health span-extending strategy
Triana-Martínez, F., Pierantoni, A., Graça, D., Bergo, V., Emelyanov, A., Gallerand, A., Grosse, L., Grigorash, B. B., Polyzou, A., Castiglione, A., et al. (2026) · Immunity · doi:10.1016/j.immuni.2026.02.013 · Cited by 10
Sfera, A., Osorio, C. P., Hazan, S., Kozlakidis, Z., Maldonado, J. C., del Campo, C. M. Z.-M., Anton, J. J., Rahman, L., Andronescu, C. V., & Nicolson, G. L. (2022) · Endocrines · doi:10.3390/endocrines3040058 · Cited by 9
Karim, A., Qaisar, R., Suresh, S., Jagal, J., & Rawas‐Qalaji, M. (2024) · Nanomedicine · doi:10.1080/17435889.2024.2393074 · Cited by 7
Medical costs of osteoporosis in the Iranian elderly patients
Alipour, V., Meshkani, Z. S., Rezapour, A., Aboutorabi, A., Bagherzadeh, R., & Saber, N. (2020) · Medical Journal of the Islamic Republic of Iran · doi:10.47176/mjiri.34.37 · Cited by 7
Low bone turnover levels predict increased risk of cancer
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Innan, H., Veitia, R. A., & Govindaraju, D. R. (2019) · Human Genetics · doi:10.1007/s00439-019-02067-9 · Cited by 7
Stojiljković, A., Gaschen, V., Forterre, F., Rytz, U., Stoffel, M. H., & Bluteau, J. (2021) · GeroScience · doi:10.1007/s11357-021-00488-x · Cited by 7
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(2021) · doi:10.21203/rs.3.rs-1034608/v1 · Cited by 6
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Lionetti, M. C., Mutti, F., Soldati, E., Fumagalli, M. R., Coccè, V., Colombo, G., Astori, E., Miani, A., Milzani, A., Dalle‐Donne, I., et al. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16040657 · Cited by 6
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Rosko, A. E., & Artz, A. S. (2017) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2017.01.002 · Cited by 5
Ways to become old: Role of lifestyle in modulation of the hallmarks of aging
Accardi, G., & Aiello, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822569-1.00009-3 · Cited by 5
Chen, R., Lei, S., & Li, G. (2025) · The Spine Journal · doi:10.1016/j.spinee.2025.01.038 · Cited by 4
Huang, Y., Qiu, Z., Jiang, C., Fang, Q., Wang, J., Han, M., Liu, Y., & Li, Z. (2025) · Scientific Reports · doi:10.1038/s41598-025-00950-2 · Cited by 4
Bersani, F. S., Canevelli, M., Imperatori, C., Barchielli, B., Prevete, E., Sciancalepore, F., Vicinanza, R., Maraone, A., Salzillo, M., Tarsitani, L., et al. (2024) · The Journal of Frailty & Aging · doi:10.14283/jfa.2024.49 · Cited by 3
Han, Y., Qiao, W., Xue, Q., Miao, D., & Zhan, D. (2024) · Stem Cells · doi:10.1093/stmcls/sxae088 · Cited by 3
Wyles, S. P., Vyas, K. S., Wasserburg, J. R., Ansaf, R. B., & Kirkland, J. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15500-0.00009-8 · Cited by 3
Self-citationSantos, J. A. D., dos Santos, S. M., Paulino, M. D., Carneiro, J. A., & da Costa, F. M. (2024) · Revista Brasileira de Geriatria e Gerontologia · doi:10.1590/1981-22562024027.230208.en · Cited by 3
Langhans, B., Strassburg, C. P., Röcken, C., & Kalthoff, S. (2025) · Oxidative Medicine and Cellular Longevity · doi:10.1155/omcl/3203439 · Cited by 2
Sarcopenia and the inflammatory cytokines
Orzechowski, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822146-4.00008-9 · Cited by 2
Senescence in Aging, Within the Brain and Other Diseases: Mechanisms and Interventions
Chakrabarti, S. K., & Chattopadhyay, D. (2023) · Exploratory Research and Hypothesis in Medicine · doi:10.14218/erhm.2023.00018 · Cited by 1
Obesity and Aging. General Aspects
Dyleva, Y. A., Belik, E. V., & Gruzdeva, O. V. (2023) · Российский физиологический журнал им И М Сеченова · doi:10.31857/s0869813923030020 · Cited by 2
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Dyleva, Y. A., Belik, E. V., & Gruzdeva, O. V. (2023) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093023020102 · Cited by 1
Senotherapeutics: Emerging pharmacological strategies to target cellular senescence
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Cordero, N. P., Schoenlein, P. V., Fulzele, S., & Hill, W. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-820088-9.00031-7 · Cited by 1
Muller’s ratchet as a mechanism of frailty and multimorbidityPreprint
Govindaraju, D. R., & Innan, H. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/439877 · Cited by 1
Rifabutin induced multinucleated hepatocytes in rats: an overview with future prospects
El‐Arabey, A. A., & Abdalla, M. (2018) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-018-3411-7 · Cited by 1
Research horizons for the twenty‐first century
Rodríguez‐Mañas, L., Assar, M. E., & Angulo, J. (2022) · Pathy's Principles and Practice of Geriatric Medicine · doi:10.1002/9781119484288.ch134 · Cited by 1
A Contraindication for Transplantation? Consequences of Frailty on Immunity and Immunosuppression
Nian, Y., Maenosono, R., Iske, J., Elkhal, A., & Tullius, S. G. (2019) · Current Transplantation Reports · doi:10.1007/s40472-019-0228-y
Stojiljković, A., Gaschen, V., Forterre, F., Rytz, U., Stoffel, M. H., & Bluteau, J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.27.217596
Libertini, G., Corbi, G., Conti, V., Shubernetskaya, O. S., & Ferrara, N. (2021) · Advances in studies of aging and health · doi:10.1007/978-3-030-73774-0_6
Faculty Opinions recommendation of Fisetin is a senotherapeutic that extends health and lifespan.
Schumacher, B. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734139615.793563345
Takayanagi, H., & Terashima, A. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.729069932.793546383
Analysis of senescent and non-senescent mortality
Agadi, R. P., Talawar, A. S., & Rangoli, A. (2023) · International Journal of Statistics and Applied Mathematics · doi:10.22271/maths.2023.v8.i6sm.1491
Santos, J. A. D., dos Santos, S. M., Paulino, M. D., Carneiro, J. A., & da Costa, F. M. (2024) · Revista Brasileira de Geriatria e Gerontologia · doi:10.1590/1981-22562024027.230208.pt
Li, Y., Meng, Y., Zhu, X., Saadiq, I. M., Jordan, K. L., Eirin, A., & Lerman, L. O. (2020) · Figshare · doi:10.6084/m9.figshare.12799293
Li, Y., Meng, Y., Zhu, X., Saadiq, I. M., Jordan, K. L., Eirin, A., & Lerman, L. O. (2020) · Figshare · doi:10.6084/m9.figshare.12799290
Li, Y., Meng, Y., Zhu, X., Saadiq, I. M., Jordan, K. L., Eirin, A., & Lerman, L. O. (2020) · Figshare · doi:10.6084/m9.figshare.12799296
Nurses as guardians of time: the hidden clinical value of continuous care in geriatrics
Yang, Y., Wang, H., Li, E., Zheng, Y., Chen, Y., & Wu, X. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1799845
Shao, Q., Chen, D., Shao, W., & Ye, Q. (2026) · Research · doi:10.34133/research.1326 · Cited by 1
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Kanbur, E., & Aydin, Ö. F. (2026) · Biogerontology · doi:10.1007/s10522-026-10489-y
Pellegrino, N., Diniz, B. S., Zhou, Y., Fortinsky, R. H., Kuchel, G. A., Brugge, D., & Kuo, C.-L. (2026) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2026.182315
Metadata
- Authors
- LeBrasseur, N. K., Tchkonia, T., & Kirkland, J. L.
- Venue
- Nestlé Nutrition Institute Workshop Series
- Publisher
- S. Karger AG
- Published
- 2015
- Volume
- 83
- Pages
- 11-18
- ISSN
- 1664-2147 (ISSN-L)
- 1664-2155
- PMC
- PMC4780350
- OpenAlex
- W1758822526
- Cited by
- 147
- References
- 31
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 12 · 2023: 17 · 2022: 9 · 2021: 26 · 2020: 20 · 2019: 19 · 2018: 12 · 2017: 12 · 2016: 7
- FWCI
- 55.80
- Type
- conference paper
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nestlé Nutrition Institute Workshop series (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mayo Clinic
- Glenn Foundation for Medical Research
- National Institutes of Health
- National Institute on Aging (AG-41122, P01AG041122)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, senescence-associated secretory phenotype, aging, frailty, age-related diseases, healthspan, chronic inflammation, hyperproliferation, population aging
- MeSH terms
- Aged, 80 and over, Aging, Chronic Disease, Humans, Inflammation, Life Style, Models, Biological, Risk Factors, Frail Elderly, Cellular Senescence, Models, Immunological, Cell Proliferation, Elder Nutritional Physiological Phenomena
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