The metabolic roots of senescence: mechanisms and opportunities for intervention

Authors: WILEY, CHRISTOPHER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CAMPISI, JUDITH - Buck Institute For Age Research

Submitted to: Nature Metabolism
Publication Type: Review Article
Publication Acceptance Date: 9/14/2021
Publication Date: 10/18/2021
Citation: Wiley, C., Campisi, J. 2021. The metabolic roots of senescence: mechanisms and opportunities for intervention. Nature Metabolism. 3:1290-1301. https://doi.org/10.1038/s42255-021-00483-8.
DOI: https://doi.org/10.1038/s42255-021-00483-8

Interpretive Summary:

Technical Abstract: Cellular senescence entails a permanent proliferative arrest, coupled to multiple phenotypic changes. Among these changes is the release of a 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.