Abstract
This review explores hibernation-inspired innovations to address major healthcare challenges, including aging and chronic diseases. The study of hibernating mammals offers unique insights into extreme metabolism that could revolutionize treatments for various conditions. Hibernation provides natural examples of reversible mass gain, insulin resistance, hypothermia, and metabolic suppression, which have direct applications to diabetes management and ischemia-reperfusion injury. The ability of hibernating animals to emerge without neuronal, muscle, or bone loss highlights potential avenues for treating neurodegenerative and age-related diseases. This review discusses the journey from discovery to translation, emphasizing the importance of understanding the phenology and physiological ecology of target species. It highlights the challenges and advancements in developing tools for non-model organisms, which have opened new opportunities for hibernation-inspired drug discovery. Hibernators' resistance to bone and muscle atrophy, combined with adaptive anorexia, offers insights for obesity. Nitrogen recycling provides strategies for treating sarcopenia and preventing ammonia toxicity. Applications of hibernation science in stroke and cardiac arrest include improvements in targeted temperature management and application of temperature-independent neuroprotection. Interbout arousals in hibernators offers insights into tolerance of rapid rewarming and reperfusion, which could inform treatments for ischemia-reperfusion injuries. This review synthesizes the potential of hibernation research in advancing biomedical innovations.