Heat acclimation and cross tolerance to hypoxia: Bridging the gap between cellular and systemic responses

Recent research has suggested a potential for some of the physiological and cellular responses to heat acclimation to carry over to improved tolerance of the novel stresses of another environment. This cross-tolerance is evident in heat-acclimated animals that exhibit enhanced tolerance to either hypoxic or ischemic stress, and is primarily attributed to shared cellular stress response pathways. These pathways include Hypoxia-Inducible Factor-1 (HIF-1) and Heat Shock Proteins (HSP). Whether these shared cellular stress response pathways translate to systemic cross-tolerance (improved exercise tolerance, reduced risk of environment-associated illness) has not been clearly shown, particularly in humans. This review highlights the HIF-1 and HSP pathways and their relationship with systemic acclimation responses, and further examines the potential cellular and systemic adaptations that may result in cross-tolerance between hot and hypoxic environments.