Differential effects of chronic overload‐induced muscle hypertrophy on mTOR and MAPK signaling pathways in adult and aged rats

Abstract

We examined activation of the mammalian target of rapamycin (mTOR) and mitogen‐activated protein kinase (MAPK) signaling pathways in adult (Y; 6 mo old; n = 16) and aged (O; 30 mo old; n = 16) male rats (Fischer 344 x Brown Norway) subjected to chronic overload‐induced muscle hypertrophy of the plantaris (PLA) and soleus (SOL) muscles. Animals underwent either 4 weeks of bilateral surgical ablation (SA) of two‐thirds of the gastrocnemius muscle or sham surgery (CON). Animals were subjected to SA to promote compensatory hypertrophy in the PLA and SOL muscles. Muscle weights of the Y CON (434 ± 39 mg; mean ± SD; p < 0.05) and Y SA (506 ± 56 mg) rats were significantly heavier than the O CON (353 ± 18 mg) and O SA (402 ± 41 mg) rats. There was a significant interaction between group and age for phosphorylated mTOR. Phosphorylated mTOR was higher in the Y SA group (4129 ± 674 A.U.; mean ± SE; p < 0.05) than in the Y CON (1582 ± 674), O SA (2063 ± 630) and O CON (2667 ± 728) groups. The ratio of phosphorylated to total mTOR was significantly higher in both SA groups than in their respective controls (0.107 ± 0.105 A.U. vs. ‐0.297 ± 0.112; p < 0.05). We also observed a significant effect of age on total p44 MAPK. It was higher in the O (17969 ± 1242; p < 0.05) than the Y (13342 ± 1242) rats. These data indicate mTOR signaling is attenuated in an aging animal model of chronic overload‐induced muscle hypertrophy. Supported by USDA 58‐1950‐7‐707, NIA AG‐25270 and DK007651.