Role of the Cytokine-like Hormone Leptin in Muscle-bone Crosstalk with Aging

The cytokine-like hormone leptin is a classic adipokine that is secreted by adipocytes, increases with weight gain, and decreases with weight loss. Additional studies have, however, shown that leptin is also produced by skeletal muscle, and leptin receptors are abundant in both skeletal muscle and bone-derived mesenchymal (stromal) stem cells. These findings suggest that leptin may play an important role in muscle-bone crosstalk. Leptin treatment in vitro increases the expression of myogenic genes in primary myoblasts, and leptin treatment in vivo increases the expression of microRNAs involved in myogenesis. Bone marrow adipogenesis is associated with low bone mass in humans and rodents, and leptin can reduce marrow adipogenesis centrally through its receptors in the hypothalamus as well as directly via its receptors in bone marrow stem cells. Yet, central leptin resistance can increase with age, and low circulating levels of leptin have been observed among the frail elderly. Thus, aging appears to significantly alter leptin-mediated crosstalk among various organs and tissues. Aging is associated with bone loss and muscle atrophy, contributing to frailty, postural instability, and the incidence of falls. Therapeutic interventions such as protein and amino acid supplementation that can increase muscle mass and muscle-derived leptin may have multiple benefits for the elderly that can potentially reduce the incidence of falls and fractures.