Sarcopenia and body temperature—the significance of interorgan metabolic networks in skeletal muscle atrophy

The skeletal muscle plays a key role in thermogenesis and energy homeostasis in endotherms. Therefore, reduced skeletal muscle mass and function are closely associated with health disorders such as obesity and hypothermia. In humans, inactivity and nutritional deficiencies can lead to skeletal muscle atrophy. However, hibernating mammals, which can greatly suppress their metabolic rate, can maintain significant skeletal muscle mass even during prolonged periods of inactivity and nutritional restriction. This review focuses on how skeletal muscle contributes to maintaining body temperature as the organ that consumes the most energy, while also contributing to whole-organism homeostasis through its high metabolic flexibility in a self-sacrificing manner. Particularly, we reconceptualized muscle atrophy associated with the thermoregulatory process in terms of inter-organ metabolic interaction, proposing that sarcopenia is an integral component of systemic energy metabolism regulation. By deepening our understanding of the functional metabolic flexibility of skeletal muscle and its regulatory mechanisms, we can redefine sarcopenia as an adaptive response that contributes to maintaining metabolic homeostasis. This perspective could provide new insights into the pathophysiology of sarcopenia and metabolic disorders, and inform the development of more effective prevention and treatment strategies.