Programmed Cell Death and its Implications for Skeletal Muscle Wasting

Skeletal muscle atrophy is an inevitable sequel of various factors such as cachexia, aging, fasting, denervation, and microgravity. It is characterized by reduced muscle protein through increased proteolysis and decreased protein synthesis. Recent research suggests that atrophy can significantly contribute to mortality among afflicted persons, and the hindrance of muscular deterioration is expected to extend lifespan. Programmed cell death or apoptosis is imperative for preserving the integrity of proliferative tissues. However, the exact role of apoptosis in post-mitotic tissues, such as skeletal muscle, remains less well-defined. Within the context of muscle atrophy, apoptosis occurs in both myonuclei as well as other types of muscle cells. The loss of muscle mass is likely attributed to the apoptotic demise of myonuclei, yet the mechanisms driving this process remain largely unknown. Both caspase-dependent and caspase-independent pathways have been implicated, with the specific mode of atrophy induction determining the apoptotic mechanisms utilized. Furthermore, it is still undetermined whether a reduction in apoptosis will ameliorate atrophy, necessitating distinct research strategies for various causes of skeletal muscle loss.