Abstract
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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C.D.W. and J.C. conceived of the concepts described in this review. C.D.W. wrote the metabolic sections with assistance from J.C. J.C. wrote the introduction with assistance from C.D.W. Both authors wrote the conclusions section.
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J.C. is a scientific founder of Unity Biotechnology, which develops senolytic therapies. C.D.W. and J.C. hold patents for induction and detection of senolysis using metabolic targets.
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Peer review information Nature Metabolism thanks David Bernard and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary handling editor: Christoph Schmitt.
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Wiley, C.D., Campisi, J. The metabolic roots of senescence: mechanisms and opportunities for intervention. Nat Metab 3, 1290–1301 (2021). https://doi.org/10.1038/s42255-021-00483-8
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DOI: https://doi.org/10.1038/s42255-021-00483-8
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