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

Magnesium (Mg²⁺), 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 Mg²⁺ deficiency with muscle regeneration dysfunction and sarcopenia in older-aged individuals, there is no consensus on the action mode and molecular mechanism by which Mg²⁺ influences aged muscle size and function. Here, we identified the appropriate Mg²⁺ 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 Mg²⁺ supplementation in aged mice significantly promotes muscle regeneration and conserves muscle mass and strength. Mechanistically, Mg²⁺ stimulation activated the mammalian target of rapamycin (mTOR) signalling, 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 Mg²⁺ supplementation in the elderly.