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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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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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