Maintaining skeletal muscle mass is essential for general health and prevention of disease progression in various neuromuscular conditions. Here we provide an innovative approach to evaluate the mechanisms underlying muscle preservation in a naturally occurring hibernating animal that is protected from muscle atrophy despite prolonged periods of immobilization and starvation. We find that absence of proteolysis and autophagy accompanied by increased protein synthesis during hibernation is regulated independent of Akt. These observations challenge the current paradigm that Akt is the major determinant and regulator of skeletal muscle mass and homeostasis. Instead, we demonstrate that serum- and glucocorticoid-inducible kinase, SGK, represents a novel mediator of skeletal muscle homeostasis and function in hibernating and non-hibernating mammals. Our results thus identify a novel therapeutic target to combat loss of skeletal muscle mass in a variety of conditions associated with muscle atrophy and degeneration. Furthermore, we will demonstrate how these pathways are regulated in cardiac muscle during hibernation and thus emphasize the versatility of biological protection of numerous tissues during prolonged periods of decreased blood flow and metabolism.