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Cross Adaptation and Cross Tolerance in Human Health and Disease

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Human physiological responses to heat, cold, hypoxia, microgravity, hyperbaria and hypobaria are well studied in isolation. However, in the natural world these stressors are often combined or experienced sequentially. Studies examining human responses to these more realistic, yet relatively complex, ...

Human physiological responses to heat, cold, hypoxia, microgravity, hyperbaria and hypobaria are well studied in isolation. However, in the natural world these stressors are often combined or experienced sequentially. Studies examining human responses to these more realistic, yet relatively complex, circumstances remain sparse, but could provide important insights into an emerging area within human physiology: cross-adaptation. Cross-adaptation occurs when exposure to one stressor induces physiological and behavioural protection to a novel stressor, without a prior exposure to the novel stressor. Seminal work from Horowitz and colleagues at the Hebrew University, Israel has provided clear indications that in animal models heat acclimation enhances neuro and cardio-protection following myocardial infarction, stroke, traumatic brain injury and concussion. This exciting physiological phenomenon is only possible through cellular protective mechanisms which are shared between stressors; with the interaction between hypoxia inducible factor 1 – alpha (HIF-1α) and stress inducible heat shock proteins (HSPs) thought to be a strong driver of both physiological cross-adaptation and cellular cross-tolerance.

Excitingly, recent human studies have indicated that both heat acclimation, and habituation to cold water immersions, may induce cross tolerance effects, with improvements in both physiological adaptation and cellular tolerance, as well as physical exercise performance observed during later hypoxic exposures. This gives rise to the possibility that cross-tolerance, and specifically HSP responses, can be manipulated to induce favourable outcomes in sporting, occupational and health contexts. The therapeutic manipulation of the heat shock response, whether via acute or prolonged heat treatment, pharmacological inducement, or exercise, may also provide novel treatment modalities for conditions characterised by metabolically induced inflammation and impaired insulin responsiveness, such as diabetes, obesity and prolonged bed rest. In support of this, rodent models of disease show heating induced increases in the heat shock response and muscular HSP72 improves insulin sensitivity, Furthermore a substantive body of data also relates HSP72 to muscle mass preservation following a period of unloading analogous to bedrest and immobilization. The constitutive levels of heat shock proteins and their ability to upregulate in response to stress are known to be reduced in the elderly and those suffering from diseases characterised by chronic low grade inflammation. Our understanding of how the elderly and those living with chronic diseases respond and adapt to altered environmental conditions is still in its infancy. Whether the potential for both adaptation to environments, and the ability to benefit from cross tolerance effects declines as we age, with and without disease is currently not known. Understanding cross tolerance and the potential therapeutic role of the heat shock response has particular contemporary relevance when the combination of increased global temperatures alongside an ageing population is considered; particularly with a growing sub population of those ageing managing chronic non-communicable diseases such as obesity and type 2 diabetes.

This Research Topic will host both applied and mechanistic original research and review contributions that examine physiological responses to combined and sequential environmental stressors in sporting, military, occupational and clinical settings. In recognition of the risk ongoing climate change poses to public health, we also provide a platform for those investigating the combined effects of ageing with and without chronic disease states on physiological tolerance, and adaptation to, altered environmental conditions.

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Keywords: Adaptation, acclimation, climate-change, heat


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