The concepts of allostasis and hormesis deal with the relationship between an organism and its environment. They may have particular relevance to frailty and could explain how early life events could have late-life consequences. Allostasis (literally meaning ''achieving stability through change'') is a dynamic regulatory process that allows the organism to adapt to the challenges of its environment. It is an extension of the concept of homeo-stasis (the ability or tendency of an organism or a cell to maintain internal equilibrium by adjusting its physiological processes). Many physiologic parameters do not remain constant but vary significantly in response to perceived stress. The neuroendocrine, autonomic nervous, and immune system responses, though beneficial in the short run, can be damaging long term if not shut down when no longer needed. Allostatic load refers to the price of the chronic overactivation of these regulatory systems (McEwen, 2003; McEwen, 2004). Although there are no studies showing a direct association with frailty, a summary measure for allostatic load was found to be an independent predictor of functional decline in the MacArthur studies of successful aging (Karlamangla, et al., 2002). Hormesis refers to the beneficial effects of low doses of potentially harmful substances. It is becoming apparent that environmental stress does more than ''cull the herd'' by eliminating the weakest individuals (Semenchenko et al., 2004). A number of mild stresses (e.g., cold, heat, irradiation, caloric restriction) have been found to be associated with increased longevity in various animal models. The proposed mechanism is that the stress induces stimulation of maintenance and repair pathways (Tattan, 2004; Radek et al., 2005). Frailty may be the long-term outcome of a complex interaction between the type, severity, and timing of environmental stresses and the nature (and consequences) of the response to these stresses.
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