CALORIE RESTRICTION AND THE AGING MUSCLE: A MULTISPECIES APPROACH

Aging is associated with a progressive decline in muscle mass, strength, and physical function termed sarcopenia. Sarcopenia is an important risk factor for loss of independence, reduced quality of life, and increased mortality. Calorie restriction (CR) is an effective dietary treatment for several age-related conditions, including sarcopenia. Recent work conducted in our laboratory suggests insulin-like growth factor-1 (IGF-1) is involved in the anti-aging effects of CR. The aim of this work is to understand the role of circulating IGF-1 in CR-induced effects on aging skeletal muscle. Using a multispecies approach, we sought to determine if IGF-1-mediated effects of CR are conserved among mice, nonhuman primates, and humans. As an extension into our investigation of CR and IGF-1 on aging muscle, we conducted an in vivo experiment to examine the role of a CR mimetic, mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition), on age-related loss of muscle strength and function. Our results suggest that the effects of CR on aging skeletal muscle are realized through biological changes consistent with regenerative and repair-related mechanisms and a shift in transcriptional profiles towards improved metabolic and inflammatory signaling pathways that promote enhanced mitochondrial function and biogenesis. Collectively, this work demonstrates CR-induced effects on aging muscle are, in part, supported by reduced circulating IGF-1. Further, the CR-mimetic, rapamycin may hold promise as a pharmacological alternative to CR to attenuate loss of muscle strength and function associated with age.