Sestrins are evolutionarily conserved mediators of exercise benefits

Authors

Myungjin Kim, University of Michigan
Alyson Sujkowski, Wayne State University School of Medicine, Detroit
Sim Namkoong, University of Michigan & Kangwon National University
Bondong Gu, University of Michigan
Tyler Cobb, Wayne State University School of Medicine, Detroit
Boyoung Kim, University of Michigan
Allison H. Kowalsky, University of Michigan
Chun-Seok Cho, University of Michigan
Ian Semple, University of Michigan
Seung-Hyun Ro, University of Michigan & University of Nebraska, LincolnFollow
Carol Davis, University of Michigan
Susan V. Brooks, University of Michigan
Michael Karin, University of California San Diego
Robert J. Wessells, Wayne State University School of Medicine, DetroitFollow
Jun Hee Lee, University of MichiganFollow

Document Type

Article

Date of this Version

2020

Citation

NATURE COMMUNICATIONS | (2020)11:190 | https://doi.org/10.1038/s41467-019-13442-5 | www.nature.com/naturecommunications

Comments

The Author(s) 2020

Abstract

Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the meta- bolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise ben- efits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance.