Decreased Activation of Akt/mTOR/GSK3 Signaling in Aged Rats Following Functional Overload

Abstract

Aging is associated with a reduced capacity to respond to growth cues that occur during resistance exercise or reloading following atrophy. The cellular and molecular mechanisms responsible for the impaired growth capacity in aging are poorly understood. Recent evidence suggests that Akt/mTOR/GSK3 mediated signaling pathways are critical for regulating muscle size in young adult animals, especially under loading conditions, through their control of protein translation. The degree to which changes in translation efficiency regulate or impair growth in aged animals is unknown. The objective of this study was to measure the activation status of Akt/mTOR/GSK3 signaling pathways in young adult (6 month) and old (30 month) male Fisher-Brown Norway rats following a chronic increase in mechanical loading. The plantaris muscle was functionally overloaded (FO) for 7 and 14 days following bilateral surgical removal of the soleus and medial/lateral gastrocnemius muscles. Muscle growth was significantly less in old versus young rats at 7 and 14 days of FO. Akt/PKB phosphorylation increased in young, but not old rats following 7 days of FO. The formation of eIF4E:eIF4G complexes significantly increased in young, but not old rats following FO. Expression of eIF2B epsilon protein significantly increased in young rats following FO. In old rats, there was a marked decrease in the upregulation of eIF2Bε expression following FO. These data suggest that the activation of Akt/mTOR/GSK3 signaling pathways is impaired in old rats during chronic loading leading to a reduction in muscle growth.