Exercise attenuates juvenile irradiation-induced skeletal muscle decline by improving calcium handling and decreasing mitochondrial stress

Abstract

Proper skeletal muscle development, maintenance, and function is necessary for movement. Decline in muscle function with age and disease is directly associated with a diminished quality of life. Radiation therapy is commonly used to treat certain forms of childhood cancer based on the cytotoxic effects of radiation on cancerous tissue. However, the adverse effects elicited by radiation are not always constrained to the diseased tissue and can accelerate muscle wasting and decline, which is particularly detrimental to juvenile cancer survivors. Exercise is effective at limiting muscle decline and improving muscle function in various diseases. Thus, we hypothesized 1 mo of voluntary endurance exercise following juvenile radiation treatment will reduce muscle damage and restore functional deficits that occur following radiation. Here, we show that following juvenile radiation, 1 mo of voluntary wheel running significantly improved muscle function in mice by promoting adaptations in intracellular calcium handling, improving mitochondrial turnover and reducing oxidative stress resulting from radiation-induced mitochondrial damage. These findings help guide caregivers in their approach to childhood cancer survivor recovery and have implications for other diseases where similar mechanisms of calcium handling and mitochondrial function are disrupted.