Osteocalcin is necessary and sufficient to maintain muscle mass in older mice

Objective: A decrease in muscle protein turnover and therefore in muscle mass is a hallmark of aging. Because the circulating levels of the bone-derived hormone osteocalcin decline steeply during aging in mice, monkeys and humans we asked here whether this hormone might regulate muscle mass as mice age. Methods: We examined muscle mass and strength in mice lacking osteocalcin (Ocn/) or its receptor in all cells (Gprc6a/) or specifically in myofibers (Gprc6a Mck /) as well as in 9 month-old WT mice receiving exogenous osteocalcin for 28 days. We also examined protein synthesis in WT and Gprc6a/ mouse myotubes treated with osteocalcin. Results: We show that osteocalcin signaling in myofibers is necessary to maintain muscle mass in older mice in part because it promotes protein synthesis in myotubes without affecting protein breakdown. We further show that treatment with exogenous osteocalcin for 28 days is sufficient to increase muscle mass of 9-month-old WT mice. Conclusion: This study uncovers that osteocalcin is necessary and sufficient to prevent age-related muscle loss in mice.