Allostasis and allostatic load

In the biology of the human living system, 'allostasis' refers to physiological mechanisms that enable the system to adjust beneficially to diverse perturbing, stressful, and potentially harmful external and internal circumstances, and thereby maintain system viability, specifically through changes in the system’s properties &mdash; its bodily state &mdash; viz., by 'adapting' the system to the stressor. Allo refers to variability; stasis, to stability &mdash; so that allostasis frequently colloquializes as "stability through change", or homeostasis through change. Allostatic mechanisms appear prominently in the central nervous system’s regulation of (a) the behavior of the system-as-a-whole (e.g., eating behavior in response to hunger stress), and (b) the physiological behavior of subsystems of the system-as-a-whole (e.g., cardiovascular function in response to predator stress). Allostatic mechanisms contribute to system homeostasis, not by restoring physiological or behavioral variables to within a fixed set-point range, but in effect by changing the optimal set-point range, at least temporarily, thereby adapting the system to the potentially harmful circumstances it currently faces. McEwen,B.S.; Stellar,E. (1993) Stress and the individual. Mechanisms leading to disease. Arch.Int.Med 153:2093-2101. PMID 8379800.  Abstract: 
 * OBJECTIVE: This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses.
 * DATA SOURCES: Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE.
 * DATA EXTRACTION: Independent extraction and cross-referencing by us.
 * DATA SYNTHESIS: Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis. In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful. [Emphasis added]
 * CONCLUSIONS: This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed. However, if the stimulus to the allostatic re-set persists, the resulting so-called allostatic load can lead to dysfunction or disease of the system.

Elaborated definitions and examples
Jeongok Logan and Debra Barksdale at the University of North Carolina Chapel Hill articulate a succinct definition of allostasis and allostatic load:

Allostasis is the extension of the concept of homeostasis and represents the adaptation process of the complex physiological system to physical, psychosocial and environmental challenges or stress. Allostatic load is the long-term result of failed adaptation or [failed] allostasis, resulting in pathology and chronic illness. Logan JG, Barksdale DJ. (2008) Allostasis and allostatic load: expanding the discourse on stress and cardiovascular disease. J.Clin.Nurs. 17:201-208. PMID 18578796.  Abstract: 
 * AIM: The aim of this discursive paper is to introduce allostasis and allostatic load, which are relatively new concepts proposed to explain physiological responses to stress, and to suggest ways in which allostasis theory can be applied to the development of clinical interventions to increase resilience for producing better health outcome.
 * BACKGROUND: Common explanations of stress have failed adequately to explicate its association with health and chronic illness. Allostasis is the extension of the concept of homeostasis and represents the adaptation process of the complex physiological system to physical, psychosocial and environmental challenges or stress. Allostatic load is the long-term result of failed adaptation or allostasis, resulting in pathology and chronic illness.
 * DISCUSSION: The concepts of allostasis and allostatic load introduced the idea that external challenges initiate allostasis and chronic stress causes allostatic load that can be measured with multiple biomarkers. Finding from several studies suggests that higher allostatic load is associated with worse health outcomes. Resilience represents successful allostasis and strategies can be implemented to enhance resilience and thereby improve health outcomes.
 * CONCLUSIONS: This theoretical model provides a comprehensive explanation of the human body's adaptation processes in response to stress and the results of failed adaptation over time. In addition, combining the concepts of allostasis and resilience may help us to understand and implement clinical strategies better to reduce or prevent the debilitating physiological and psychological effects of chronic stress and chronic illness.
 * RELEVANCE TO CLINICAL PRACTICE: Clinical practice should be based on a solid theoretical foundation to improve health outcomes. Strategies to manage stress and increase resilience along with clinical interventions to manage the physiological responses to chronic stress are necessary to assist in preventing and controlling the detrimental effects of chronic disease on human life.

Bruce McEwen and Teresa Seeman, in collaboration with the Allostatic Load Working Group, elaborate and give specific examples:

For each system of the body, there are both short-term adaptive actions (allostasis) that are protective and long-term effects that can be damaging (allostatic load). For the cardiovascular system, a prominent example of allostasis is the role of catecholamines in promoting adaptation by adjusting heart rate and blood pressure to sleeping, waking, physical exertion (citation). Yet, repeated surges of blood pressure in the face of job stress or the failure to shut off blood pressure surges efficiently accelerates atherosclerosis and synergizes with metabolic hormones to produce Type II diabetes, and this constitutes a type of allostatic load (see (citation)). Closely related to this is the role of adrenal steroids in metabolism. Whereas adrenal steroids promote allostasis by enhancing food intake and facilitating the replenishment of energy reserves, the overactivity of this system involving repeated HPA activity in stress or elevated evening cortisol leads to allostatic load in terms of insulin resistance, accelerating progression towards Type II diabetes, including abdominal obesity, atherosclerosis, and hypertension (citations). In the brain, actions of adrenal steroids and catecholamines that are related to allostasis include promoting retention of memories of emotionally-charged events, both positive and negative. Yet, overactivity of the HPA axis together with overactivity of the excitatory amino acid neurotransmitters promotes a form of allostatic load, consisting of cognitive dysfunction by a variety of mechanisms that involve reduced neuronal excitability, neuronal atrophy and, in extreme cases, death of brain cells, particularly in the hippocampus (citations).

McEwen and Seeman divide allostatic load into several distinct types of scenarios:
 * Stress overload, such as that caused by severe and repeated economic burdens, which potentially leads to physical and mental dysfunctions;
 * Stress adaptation failure, where mediators of a stress response fail to diminish in response to repeated similar stress events, such as repeated taking of exams during course work;
 * Stress response persistence following cessation of the stressor;
 * Stressors that chronically disturb normal circadian rhythms, such as sleep deprivation;
 * Stress response inadequacy that leads to overreaction of other systems.

In their book on the endocrine factors in aging, Derek Chadwick and Jamie Goode characterize allostasis as follows, and contrast it with homeostasis:

 Speaking generally, allostasis is distinct from homeostasis in maintaining a compensated equilibrium rather than a physiological equilibrium: stability is maintained at a price. The allostatic set point is abnormal relative to the homeostatic set point, the system is inherently less stable, and it has a relatively narrow dynamic range. Finally, a system in allostasis leads to pathology whereas a system in homeostasis does not.

Chadwick and Goode go on to compare the pathology and regulatory dysfunctions caused by chronic stress (allostatic load) and by the aging process. The consider the findings supportive of the notion that allostatic load plays a role in determining longevity. They point to evidence that similar disturbances in aging and chronic stress occur in the daily rhythm of the brain's interactions between its hypothalamus and pituitary gland, and in body temperature regulation, drawing attention to allostatic load as a factor in aging.

Role of brain in the physiology and neurobiology of stress
Holding ref:

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