Allostasis differs from homeostasis Vis-a` -Vis its emphasis on dynamic rather than static biological set-points, considerations of the brain’s role in feedback regulation, and view of health as a whole-body adaptation to contexts (Schulkin, 2003b). These insights have encouraged new ways of conceptualizing complex, multi-systemic biological activities where, as Heraclitus wrote, ‘‘the only constant is change’’. The allostatic load model expands the theory of allostasis by applying it to the cause and effects of chronic stress… Allostatic load (AL) represents the ‘wear and tear’ the body experiences when repeated allostatic responses are activated during stressful situations (McEwen and Stellar, 1993). Real or interpreted threats to homeostasis initiate the sympathetic– adrenal–medullary (SAM) axis release of catecholamines and the hypothalamic–pituitary–adrenal (HPA) axis secretion of glucocorti- coids that mobilize energy necessary for fight-or-flight responses (Sapolsky et al., 2000)… While adaptive acutely, chronic over-activation of SAM- and HPA-axis products induce a ‘domino effect’ on interconnected biological systems that overcompensate and eventually collapse themselves, leaving the organism susceptible to stress-related diseases (Korte et al., 2005; Lupien et al., 2006; McEwen, 1998b)… A key feature of allostasis, AL, and ultimately allostatic overload is that multiple mediators of adaptation are involved and interconnected in a non-linear network… At first, prolonged secretion of the stress hormones epinephrine, norepinephrine, and cortisol (antagonized by dehydroepiandosterone) can falter in their ability to protect the distressed individual and instead begin to damage the brain and body (McEwen, 2006a)… Over time, subsidiary biological systems compensate for the over and/or under production of primary mediators and in turn shift their own operating ranges to maintain abated chemical, tissue, and organ functions. This prodromal stage is referred to as the secondary outcomes, whereby metabolic (e.g., insulin, glucose, total cholesterol, high density lipoprotein cholesterol, triglycerides, visceral fat depositing), cardiovascular (e.g., systolic and diastolic blood pressure), and immune (e.g., fibrinogen, c-reactive protein (CRP)) parameters reach sub-clinical levels. The final stage of AL progression is allostatic overload, whereby the culmination of physiological dysregulations leads to disordered, diseased, and deceased endpoints referred to as tertiary outcomes.


The allostatic load model expands the stress-disease literature by proposing a temporal cascade of multi-systemic physiological dysregulations that contribute to disease trajectories. By incorporating an allostatic load index representing neuroendocrine, immune, metabolic, and cardiovascular system functioning, numerous studies have demonstrated greater prediction of morbidity and mortality over and beyond traditional detection methods employed in biomedical practice. This article reviews theoretical and empirical work using the allostatic load model vis-à-vis the effects of chronic stress on physical and mental health. Specific risk and protective factors associated with increased allostatic load are elucidated and policies for promoting successful aging are proposed.