Peter Stenvinkel Peter Stenvinkel Peter Kotanko Peter Kotanko Johanna Painer-Gigler Johanna Painer-Gigler Paul G. Shiels Paul G. Shiels Pieter Evenepoel Pieter Evenepoel Leon Schurgers Leon Schurgers Barbara Natterson-Horowitz Barbara Natterson-Horowitz Szilvia Kalogeropoulu Szilvia Kalogeropoulu Joshua Schiffman Joshua Schiffman Richard J. Johnson Richard J. Johnson Springer 2026 This review explores the remarkable metabolic adaptations of species that thrive in extreme environments, providing insights into their resilience, flexibility and disease resistance. Species such as hibernating brown bears, migratory birds, cavefish, Greenland sharks and naked mole rats exhibit unique metabolic traits that challenge conventional paradigms of metabolic regulation. These adaptations, including resistance to hypoxia and metabolic ageing, offer potential solutions to human metabolic disorders, including obesity, type 2 diabetes and CVD. Insights from comparative physiology, particularly the mechanisms by which animals cope with food scarcity, extreme temperatures and hypoxia, could help identify novel therapeutic targets for advancing human health. For example, hibernation can serve as a model for understanding metabolic diseases, providing insights into reversible insulin resistance and energy homeostasis. This review also highlights the impact of environmental stressors, including climate change, on these species, which may jeopardise their survival despite their resilience. Accelerating anthropogenic environmental change threatens even the most resilient animal species. We call for a holistic approach to conservation and environmental protection to preserve these species and the valuable lessons they offer for managing our metabolic health. PDFDocument eng 2026-07-13T09:27:58.228618806Z 2026 Biomimetics Cardiovascular Disease Climate Change Comparative Physiology Exposome Hibernation Insulin Resistance Longevity Metabolic Adaption NrF2 Planetary Health Review 1390548 b application/pdf http://creativecommons.org/licenses/by/4.0/