Hyperactive mTORC1 signaling is unaffected by metformin treatment in aged skeletal muscle

Introduction: Appropriate activation of growth signaling pathways, specifically mammalian target of rapamycin complex 1 (mTORC1), is central to muscle mass and metabolism. The goal of these studies was to examine the effects of metformin on mTORC1 signaling in aged skeletal muscle in an attempt to normalize growth signaling. Methods: Aged (23m) and young (3m) male mice were fed a low fat diet without or with 0.5% metformin for up to 8 weeks, then mTORC1-related signaling was examined in the plantar flexor complex. Results: Metformin had no significant effect on lowering body weight or muscle mass in aged animals, nor altered p70 S6 Kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation. However, it significantly (P<0.05) reduced body weight and lowered S6K1 and rpS6 phosphorylation in the young. Conclusions: Collectively, these data suggest metformin is ineffective at normalizing growth signaling in aged skeletal muscle.