Abstract: Understanding the genetic basis of adaptation has broad implications not only for a basic understanding of evolution, but also for human pathologies given that many human diseases are a consequence of mis-adaptation to modern societies. Cavefish have acquired impressive metabolic adaptations to the food deprived cave environments, such as hyperphagia and insulin resistance. Remarkably, none of these phenotypes are leading to measurable health disadvantages, even when fed ad libitum in the laboratory environment. We hypothesize that cavefish must have co-evolved factors helping them to mitigate the otherwise detrimental health and lifespan effects usually associated with such drastic metabolic alterations. As such, we propose cavefish as a novel system which offers the possibility of identifying genetic pathways that can be protective under extreme nutritional situations, and hence, of someday developing therapies that would limit the impact of these conditions on the health of patients.