The DOI matches its Crossref record; 216 of the 216 references it cites were found in a registry or an index.
The metabolic roots of senescence: mechanisms and opportunities for intervention
Open accessAbstract
Cellular senescence entails a permanent proliferative arrest, coupled to multiple phenotypic changes. Among these changes is the release of numerous biologically active molecules collectively known as the senescence-associated secretory phenotype, or SASP. A growing body of literature indicates that both senescence and the SASP are sensitive to cellular and organismal metabolic states, which in turn can drive phenotypes associated with metabolic dysfunction. Here, we review the current literature linking senescence and metabolism, with an eye toward findings at the cellular level, including both metabolic inducers of senescence and alterations in cellular metabolism associated with senescence. Additionally, we consider how interventions that target either metabolism or senescent cells might influence each other and mitigate some of the pro-aging effects of cellular senescence. We conclude that the most effective interventions will likely break a degenerative feedback cycle by which cellular senescence promotes metabolic diseases, which in turn promote senescence.
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“The composition and strength of the SASP can vary depending on the duration of senescence, the origin of the senescence stimulus and specific cell types17,21.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [21]
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“is characterized by morphological and functional changes, including enlarged cell size,9,10 nuclear changes,11,12,13,14,15 metabolic remodeling,16 and the SASP.”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [16]
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1 retracted
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RetractedFerroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
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The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
Chronic inflammation in the etiology of disease across the life span
Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0675-0 · Cited by 4,915
Self-citationPleiotropy, natural selection, and the evolution of senescence.
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Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891
Self-citationCellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225
Self-citationAging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954
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Mitochondrial dysfunction in cell senescence and aging
Miwa, S., Kashyap, S., Chini, E., & von Zglinicki, T. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158447 · Cited by 1,061
Cellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631
SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408
“Mitochondrial dysfunction-associated senescence is primarily driven by the accumulation of cytosolic NADH, leading to ATP depletion and AMPK activation and cell cycle arrest 21 .”
Self-citationNan, L., Guo, P., Hui, W., Xia, F., & Yi, C. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1592596 · Cited by 84
Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59
Metadata
- Authors
- Wiley, C. D., & Campisi, J.
- Affiliations
- Tufts University (US)
- Buck Institute for Research on Aging (US)
- Corresponding author
- Wiley, Christopher D.
- Venue
- Nature Metabolism
- Published
- 2021-10-18
- Volume
- 3
- Issue
- 10
- Pages
- 1290-1301
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC8889622
- OpenAlex
- W3206142581
- Cited by
- 691
- References
- 216
- Citations by year
- 2026: 144 · 2025: 191 · 2024: 163 · 2023: 121 · 2022: 69 · 2021: 2
- FWCI
- 11.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- United States Department of Agriculture | Agricultural Research Service (8050-51000-099-01S)
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG051729)
- 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, cellular metabolism, metabolic dysfunction, senescence induction, senolytics, metabolic disorders, aging, proliferative arrest
- MeSH terms
- Animals, Autophagy, Homeostasis, Humans, Hyperglycemia, Lysosomes, Metals, NAD, Cellular Senescence
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