Expression of sestrins in skeletal muscle with acute exercise and aging

Abstract

Regular exercise can maintain skeletal muscle mass as we age. However, the molecular mechanisms that contribute to muscle health with exercise are incompletely defined. Recently, a group of three p53‐regulated proteins called Sestrins (Sesn1–3) have been identified. Whether these proteins are altered with age, or are induced by acute exercise in muscle is currently unknown. Thus, the purposes of our investigation were to determine: 1) if Sesns are expressed in the presence or absence of p53 after acute exercise, and 2) whether the expression of Sesns is altered in aging muscle. p53 wild‐type (WT) and knock‐out (KO) mice were run on a treadmill for 90mins and either sacrificed immediately or allowed to recover for 3hrs. Basally, muscle from p53 KO animals had 27% lower mRNA expression of Sesn2, while Sesn1 mRNA was increased by 2.3‐fold compared to WT animals. Acute exercise had no effect on Sesn2 expression, but resulted in a 1.9‐fold increase in Sesn1 which was evident in the recovery phase, but only in WT animals. To examine the effect of age, muscle from 6‐ and 36‐month old rats was analyzed. Aged animals displayed 71% and 26% reductions in Sesn1 and Sesn2 mRNA, respectively, compared to younger animals. Similar trends were observed at the protein level. Our results suggest that Sesn expression is reduced with age, and that Sesn1 can be induced by acute exercise in a p53‐dependent manner. Supported by NSERC.