Mitochondria: Are they causal players in cellular senescence?
Open accessAbstract
Cellular senescence entails an irreversible cell-cycle arrest characterised by drastic cytomorphological and metabolic changes. In recent years, the implications of cellular senescence in physiological and pathological settings, such as ageing and cancer, have gained firm ground. It is, therefore, important to understand the mechanisms underpinning the establishment and maintenance of senescence. Age-dependent alterations in cellular metabolic processes are greatly driven by changes in mitochondrial function and homeostasis. Classically, mitochondrial dysfunction has been implicated in cellular senescence mainly by promoting oxidative damage-induced cell-cycle arrest; however, emerging data suggests that other mitochondrial-dependent factors play an important role in the induction of senescent phenotypes. Here we review the role of mitochondrial homeostatic mechanisms, mitochondrial metabolites and ROS generation in the signalling pathways leading to the induction and maintenance of cellular senescence and discuss how this may contribute to the ageing process. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.
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Cellular senescence appeared to mainly be a consequence of telomere shortening, but this assumption has gradually been evolved by numerous studies showing that the senescent phenotype derived also from other stresses such as oxidative stress, genomic damage, and activation of inflammatory features.
“At first, cellular senescence appeared to mainly be a consequence of the telomere shortening [102], but this assumption has gradually been evolved by numerous studies showing that the senescent phenotype derived also from other stresses such as oxidative stress, genomic damage, and activation of inflammatory features (Figure 1) [103].”
From Role of Age-Related Mitochondrial Dysfunction in Sarcopenia (2020) · cites this paper as [103]
Senescent cells show disturbed mitochondrial metabolite balance and reduced fatty acid oxidation, causing lipids to accumulate.
“Moreover, cells undergoing senescence display altered mitochondrial metabolite homeostasis96, as well as decreased fatty acid oxidation, leading to accumulation of lipids97.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [96]
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Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Davalli, P., Mitic, T., Caporali, A., Lauriola, A., & D’Arca, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3565127 · Cited by 1,059 · see citing works
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis
Grootaert, M. O. J., Moulis, M., Roth, L., Martinet, W., Vindis, C., Bennett, M. R., & De Meyer, G. R. Y. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy007 · Cited by 606 · see citing works
Ageing, Cellular Senescence and Neurodegenerative Disease
Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · see citing works
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351 · see citing works
Role of Age-Related Mitochondrial Dysfunction in Sarcopenia
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Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16high Cells In Vivo
Omori, S., Wang, T.-W., Johmura, Y., Kanai, T., Nakano, Y., Kido, T., Susaki, E. A., Nakajima, T., Shichino, S., Ueha, S., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.09.006 · Cited by 194 · see citing works
Lai, P., Liu, L., Bancaro, N., Troiani, M., Calì, B., Li, Y., Chen, J., Singh, P. K., Arzola, R. A., Attanasio, G., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.03.005 · Cited by 174 · see citing works
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Senescence and senotherapeutics: a new field in cancer therapy
Myrianthopoulos, V., Evangelou, K., Vasileiou, P. V. S., Cooks, T., Vassilakopoulos, T. P., Pangalis, G. A., Kouloukoussa, M., Kittas, C., Georgakilas, A. G., & Gorgoulis, V. G. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.08.006 · Cited by 160 · see citing works
Lee, J. H., Yoon, Y. M., Song, K., Noh, H., & Lee, S. H. (2020) · Aging Cell · doi:10.1111/acel.13111 · Cited by 97 · see citing works
Senescent Microglia: The Key to the Ageing Brain?
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Mitochondria and cellular senescence: Implications for musculoskeletal ageing
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Self-citationHIV TAT-mediated microglial senescence: Role of SIRT3-dependent mitochondrial oxidative stress
Thangaraj, A., Chivero, E. T., Tripathi, A., Singh, S., Niu, F., Guo, M.-L., Pillai, P., Periyasamy, P., & Buch, S. (2021) · Redox Biology · doi:10.1016/j.redox.2020.101843 · Cited by 76 · see citing works
Fard, A. T., Leeson, H., Perez, J. A., Pietrogrande, G., Power, D., Inclan, C. L. G., Zheng, H., Nelson, C., Soheilmoghaddam, F., Glass, N., et al. (2022) · doi:10.1101/2022.01.24.476823 · Cited by 3 · see citing works
- Authors
- Correia-Melo, C., & Passos, J. F.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Passos, João F.
- ORCID
- Passos, João F.
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 1847
- Issue
- 11
- Pages
- 1373-1379
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2173281420
- Cited by
- 160
- References
- 141
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 11 · 2023: 15 · 2022: 16 · 2021: 12 · 2020: 21 · 2019: 8 · 2018: 20 · 2017: 10 · 2016: 24 · 2015: 6
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- BBSRC (BB/K017314/1)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, mitochondria, mitochondrial dysfunction, mitochondrial homeostasis, mitochondrial metabolites, reactive oxygen species, oxidative damage, cell cycle arrest, aging, cancer
- MeSH terms
- Animals, Electron Transport, Homeostasis, Humans, Mitochondria, Cellular Senescence, Reactive Oxygen Species
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.
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