The Role of SIRT3 in Exercise and Aging

Lei Zhou, Ricardo Pinho, Yaodong Gu, Zsolt Radak*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The health benefits of regular exercise are well established. Nonetheless, the molecular mechanism(s) responsible for exercise-induced health benefits remain a topic of debate. One of the key cell-signaling candidates proposed to provide exercise-induced benefits is sirtuin 3 (SIRT3). SIRT3, an NAD+ dependent mitochondrial deacetylase, positively modulates many cellular processes, including energy metabolism, mitochondrial biogenesis, and protection against oxidative stress. Although the exercise-induced change in SIRT3 signaling is a potential mechanism contributing to the health advantages of exercise on aging, studies investigating the impact of exercise on SIRT3 abundance in cells provide conflicting results. To resolve this conundrum, this narrative review provides a detailed analysis of the role that exercise-induced changes in SIRT3 play in providing the health and aging benefits associated with regular physical activity. We begin with an overview of SIRT3 function in cells followed by a comprehensive review of the impact of exercise on SIRT3 expression in humans and other mammalians. We then discuss the impact of SIRT3 on aging, followed by a thorough analysis of the cell-signaling links between SIRT3 and exercise-induced adaptation. Notably, to stimulate future research, we conclude with a discussion of key unanswered questions related to exercise, aging, and SIRT3 expression.

Original languageEnglish
Article number2596
Issue number16
Publication statusPublished - 2022 Aug


  • SIRT3
  • aging
  • exercise
  • metabolism
  • redox balance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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