Torpor and hibernation are powerful hypometabolic strategies that allow animals to survive periods of low resource availability and weather challenge. The torpid state favors an energy-saving strategy, involving a controlled reduction in metabolic rate and body temperature. It is also characterized by numerous adaptive physiological, cellular and molecular processes, some of which are triggered to protect key organs of hibernators, including their cardiovascular and musculo-skeletal systems.
Although all hibernators preserve their muscle mass and muscle strength in the face of conditions known to trigger atrophy in humans (food deprivation and physical inactivity), the champion remains the Bear 1. Apart from the strong suggestion of nitrogen recycling via urinary urea or specific organ cycles 2; 3, the balance between protein synthesis and degradation appears to be maintained during bear hibernation through global downregulation of muscle protein turnover 4. Several key mechanisms for muscle preservation have been proposed, including an antioxidant strategy 5, a myogenic microRNA response promoting activation of protein synthesis pathways and inhibition of certain protein degradation pathways 6, and maintenance of an active Cori cycle 7; 8. A particular proteomic signature also led to suggestions of the possible role of increased docosahexaenoic acid levels 7, and the maintenance of prostaglandin levels in skeletal muscles from hibernating brown bears has been proposed to play a role in muscle sparing 9. Finally, the existence of circulating anti-atrophy factors capable of acting on human muscle cells to make them grow faster 10, and on mouse cardiomyocytes to protect them against hypoxia-reoxygenation stress 11 has been reported. Those anti-atrophy factors have not been identified yet, however, they may involve agonists or antagonists of the transforming growth factor beta (TGF-b) and bone morphogenetic protein (BMP) pathways 12; 13, and several hormones and cytoprotective metabolites 1.
Elucidating the adaptive mechanisms that enable bears to cope safely with adverse seasonal conditions will undoubtedly feed innovation in the treatment of muscle but also bone, kidney and cardiovascular diseases. The benefits will help improve the health conditions of, for example, sedentary or elderly people, or astronauts.
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