Autophagy signaling following denervation‐induced muscle disuse in young and old animals

Abstract

Contractile activity is required to maintain both muscle mass and function. Decreases in muscle activity lead to atrophy, which is exacerbated by the loss of autophagy signaling. Consequently, autophagy appears to be activated to preserve muscle mass. We wished to establish whether autophagy was increased during disuse-induced muscle atrophy, and whether this was accelerated during aging-induced sarcopenia. Thus, muscle mass and autophagic proteins were compared in young (5mo) and old (35 mo) Fischer BN rats following 7 days of denervation. Muscle mass was decreased by 53% in old compared to young animals, indicating sarcopenia. However, denervation resulted in a 2-fold greater loss of muscle mass in young compared to old animals. Basal levels of autophagy regulators such as ULK1, LC3II, and ATG 7 were 1.5- to 3-fold greater in muscles of old animals. Denervation induced 4- to 5-fold increases in these proteins in young animals, but only 2-fold increases were evident in old animals. Interestingly, autophagy protein expression in both the young and old animals reached similar peak levels. These data suggest that: 1) the loss of contractile activity induces greater atrophy in young, compared to old animals, 2) autophagy signaling is elevated in muscle of old animals, and 3) denervation-induced disuse appears to provoke similar levels of autophagic signaling regardless of age.