Chronic overload induced hypertrophy is associated with age‐related muscle mass loss and diminished mTOR signaling

Abstract

The purpose of this study was to assess activation of the mTOR signaling pathway in young and aging rats in response to chronic muscle overload. Young (6 mo; n = 16) and older (30 mo; n = 23) male rats (F344×BN) were subjected to 4 weeks of bilateral surgical ablation (SA) of two‐thirds of the gastrocnemius muscle to promote compensatory hypertrophy in the plantaris (PLA) and soleus (SOL) or a sham surgery (CON). A significant interaction (p= 0.00) was found between group (SA vs. CON) and age (6mo. vs. 30mo.) when examining the normalized muscle weights (muscle weight/final body weight) of the PLA and SOL. The PLA muscle mass (mean ± SD) following SA was heavier in young rats when compared to aging rats (1.34 ± 0.07 g muscle weight/g body weight vs. 0.79 ± 0.08; p=0.00). An equivalent pattern was observed in the SOL in response to SA (0.52 ± 0.04 vs. 0.34 ± 0.04; p=0.00). Phosphorylation of p70S6Kin the SOL and PLA was similar in both young and aging rats when comparing SA (n=4) versus CON (n=4) (SOL: 6 mo; 0.21 ± 0.14 A.U. vs. 0.10 ± 0.10, 30mo; 0.20 ± 0.19 vs. 0.10 ± 0.06, PLA: 6 mo; 0.04 ± 0.02 vs. 0.02 ± 0.02, 30 mo; 0.06 ± 0.06 vs. 0.05 ± 0.01). These data indicate that aging muscle in rats is less responsive to hypertrophy in the PLA and SOL, which may be caused by impairment in mTOR signaling. Supported by USDA 58‐1950‐7‐707 and NIA AG‐25270