Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin

The mechanisms underlying age-related loss of muscle and bone tissue are poorly understood but are thought to involve changes in sex hormone status, physical activity, and circulating levels of inflammatory cytokines. This study attempts to develop an animal model useful for evaluating these mechanisms in vivo. Male C57BL/6 mice were included for study at 3, 6, 12, 18, 24, and 29 months of age. Endocortical mineralizing surface, serum leptin, body weight, and percentage of body fat all increased between 6 and 12 months of age as activity level declined. Serum levels of the inflammatory marker IL-6 increased significantly after 12 months of age, following the observed increase in body weight and percent body fat. Hindlimb muscle mass declined significantly between 18 and 24 months of age, both absolutely and relative to total body mass, with a further decline (∼15%) between 24 and 29 months. Loss of muscle mass after 18 months of age was accompanied by a significant increase in bone resorption, as indicated by serum pyridinoline cross-links, and a significant decrease in fat mass, serum leptin, bone strength, bone mineral density, and vertical cage activity. No significant changes in serum testosterone with aging were detected in the mice, as levels were essentially constant between 6 and 29 months. Our data show that mice lose a significant amount of muscle and bone tissue with age, and this loss of musculoskeletal tissue is accompanied by a drop in serum leptin and preceded by a significant decrease in physical activity.