Abstract
Adaptive Homeostasis has been defined as, "The transient expansion or contraction of the homeostatic range in response to exposure to sub-toxic, non-damaging, signaling molecules or events, or the removal or cessation of such molecules or events." (Davies, 2016). I propose that one of the most significant examples of adaptive homeostasis may be the adaptation of the cardiovascular system to exercise training. In particular, endurance type training involves the generation of increased levels of free radicals such as ubisemiquinone, superoxide, nitric oxide, and other (non-radical) reactive oxygen species such as hydrogen peroxide (H(2)O(2)), in a repetitive manner, typically several times per week. As long as the training intensity and duration are sub-maximal and not exhaustive these reactive species do not cause damage, but rather activate signal transduction pathways to induce mitochondrial biogenesis-the foundation of increased exercise endurance. Particularly important are the NFκB and Nrf2 signal transduction pathways which respond to reactive oxygen and nitrogen species generated during exercise. As with other examples of adaptive homeostasis the effects are transient, lasting only as long as the training is maintained. Unfortunately, the ability to adapt to exercise training declines with age, perhaps as a result of impaired Nrf2 and NFκB signaling, as does adaptive homeostasis capacity in general. Since this is an Hypothesis/Theory Paper and not a review, I have not tried to provide a comprehensive discussion of all the literature relating to exercise adaptation and the cardiovascular system. Rather, I have attempted to develop the Hypothesis or Theory that adaptive homeostasis is the foundation for adaptation of the cardiovascular system to exercise training, largely based on work from my own laboratory, that of close collaborators, and that of key contributors over a period of almost 40 years.