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 metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. 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.
Highlights
Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation
We established a protocol for endurance training and measuring physical endurance in Drosophila, which represents the first chronic exercise model in an invertebrate system[27]
Exercise did not increase running endurance, flight performance and AKT phosphorylation in dSesn-null flies (Fig. 1b–d). These results indicate that Sestrin is necessary for improving endurance and flight performance after exercise
Summary
Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. We show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Endurance training leads to increased mitochondrial biogenesis/efficiency[8], decreased triglyceride storage[9], improved insulin sensitivity[10], and protection of both muscle and neural functions[11] These changes are often thought to be at least partially mediated by exercise-induced upregulation of AMP-activated protein kinase (AMPK) and the insulin-AKT pathway[12]. These remodeling events lead to increased physiological capacity in both cardiac and skeletal muscle.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
