Magnesium supplementation enhances mTOR signaling to facilitate myogenic differentiation and improve aged muscle performance.

Magnesium (Mg), as an essential mineral, supports and sustains the health and activity of the organs of the human body. Despite some clinical evidence on the association of Mg deficiency with muscle regeneration dysfunction and sarcopenia in older-aged individuals, there is no consensus on the action mode and molecular mechanism by which Mg influences aged muscle size and function. Here, we identified the appropriate Mg environment that promotes the myogenic differentiation and myotube hypertrophy in both C2C12 myoblast and primary aged muscle stem cell (MuSC). Through animal experiments, we demonstrated that Mg supplementation in aged mice significantly promotes muscle regeneration and conserves muscle mass and strength. Mechanistically, Mg stimulation activated the mammalian target of rapamycin (mTOR) signaling, inducing the myogenic differentiation and protein synthesis, which consequently offers protections against the age-related decline in muscle regenerative potential and muscle mass. These findings collectively provide a promising therapeutic strategy for MuSC dysfunction and sarcopenia through Mg supplementation in the elderly.