Comparative Pathophysiology of Humans and Hibernating Bears: From Metabolic Failure to Adaptive Resilience

Modern medicine has struggled to cope with the pathologies induced by sedentary lifestyles and excess calories. As hibernating bears are remarkably resilient to such complications, this review compares the pathophysiology of the two across three critical domains. While humans experience inflammatory adipose hypertrophy, bears control obesity by utilizing immunomodulatory lipids and the hyperplastic expansion of adipose tissue. Unlike catabolism and nitrogenous waste accumulation, which are typical of human muscles, bears employ a gut microbiota-based urea recycling system to preserve proteostatic integrity. Finally, bears bypass stasis-induced thromboembolism and disuse-induced osteoporosis through targeted molecular reprogramming, including the suppression of heat shock protein 47 and balanced bone remodeling. An analysis of these divergent responses helped identify the mechanisms underlying adaptive resilience in bears, which serves as a blueprint for hibernation-inspired medicine. The translation of these evolutionary strategies, -from target-specific antithrombotics to metabolic toggling, -offers tremendous potential for treating metabolic failure, sarcopenia, and the degenerative diseases associated with chronic immobility in humans.