Caloric restriction attenuates developmental myosin heavy chain expression and myostatin signaling in aged muscles

Abstract

Aging is associated with an accumulation of muscle fibers expressing developmental myosin heavy chain (dMHC), suggesting they are in the process of regenerating. The cleaved form of myostatin increases in aged muscles and may be involved in impairing regeneration. Since caloric restriction (CR) slows age‐related muscle atrophy, we sought to determine the effect of CR on dMHC expression and to examine how this related to the myostatin signaling pathway. The gastrocnemius muscle from young adult (YA), late middle aged (LMA) and senescent (SEN) ad libitum fed and CR rats was harvested for either dMHC expression in situ or myostatin and ACVR2 receptor expression by Western immunoblot. CR attenuated dMHC expression with aging and although it did not affect the increase in cleaved myostatin, it slowed the increase in one of its receptors, ACVR2. Since the degree of muscle atrophy with aging correlated (r2=0.72) with the proportion of dMHC positive fibers, our results suggest that CR attenuates age‐related muscle atrophy by limiting the accumulation of incompletely regenerated muscle fibers secondary to attenuated myostatin signaling in aged muscles.Supported by AHFMR and CIHR.