Allostasis and allostatic load

In the biology of the human living system, allostasis refers to physiological mechanisms that enable the system to adjust to diverse perturbing, stressful, and potentially harmful circumstances, and thereby maintain system viability, specifically through changes in the system’s properties, its bodily state — 'adaptation'. Allo refers to variability; stasis, to stability — so that allostasis frequently colloquializes as "stability 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 variable to within an optimal set-point range, but in effect by changing the optimal set-point range, at least temporarily, to adapt to the potentially harmful circumstances the system faces.^[1] ^[2] ^[3] However, if the stimulus to the allostatic re-set persists, the resulting allostatic load can lead to dysfunction or disease of the system.

Bruce McEwen and Teresa Seeman, in collaboration with the Allostatic Load Working Group, give these 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).^[4]

References

Citations and notes

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↑
McEwen BS. (1998) Stress, adaptation, and disease. Allostasis and allostatic load. Ann.N.Y.Acad.Sci. 840:33-44. PMID 9629234.
- Abstract
- Adaptation [of the organism] in the face of potentially stressful challenges involves activation of neural, neuroendocrine and neuroendocrine-immune mechanisms.
- This has been called "allostasis" or "stability through change" by Sterling and Eyer (Fisher S., Reason J. (eds): Handbook of Life Stress, Cognition and Health. J. Wiley Ltd. 1988, p. 631), and allostasis is an essential component of maintaining homeostasis.
- When these adaptive systems are turned on and turned off again efficiently and not too frequently, the body is able to cope effectively with challenges that it might not otherwise survive.
- However, there are a number of circumstances in which allostatic systems may either be overstimulated or not perform normally, and this condition has been termed "allostatic load" or the price of adaptation (McEwen and Stellar, Arch. Int. Med. 1993; 153: 2093.).
- Allostatic load can lead to disease over long periods.
- Types of allostatic load include:
(1) frequent activation of allostatic systems;

(2) failure to shut off allostatic activity after stress;

(3) inadequate response of allostatic systems leading to elevated activity of other, normally counter-regulated allostatic systems after stress.
- Examples will be given for each type of allostatic load from research pertaining to autonomic, CNS, neuroendocrine, and immune system activity.
- The relationship of allostatic load to genetic and developmental predispositions to disease is also considered.
↑ Sterling P. Eyer J. (1998) Allostasis: A New Paradigm to Explain Arousal Pathology. In: Handbook of life stress, cognition, and health. Eds., Shirley Fisher and James Reason. Chichester: Wiley. ISBN 0471912697
↑
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.
↑ Bruce McEwen and Teresa Seeman in collaboration with the Allostatic Load Working Group. (1999) Allostatic Load and Allostasis.

[mcewen1998-1] McEwen BS. (1998) Stress, adaptation, and disease. Allostasis and allostatic load. Ann.N.Y.Acad.Sci. 840:33-44. PMID 9629234.
Abstract

Adaptation [of the organism] in the face of potentially stressful challenges involves activation of neural, neuroendocrine and neuroendocrine-immune mechanisms.

This has been called "allostasis" or "stability through change" by Sterling and Eyer (Fisher S., Reason J. (eds): Handbook of Life Stress, Cognition and Health. J. Wiley Ltd. 1988, p. 631), and allostasis is an essential component of maintaining homeostasis.

When these adaptive systems are turned on and turned off again efficiently and not too frequently, the body is able to cope effectively with challenges that it might not otherwise survive.

However, there are a number of circumstances in which allostatic systems may either be overstimulated or not perform normally, and this condition has been termed "allostatic load" or the price of adaptation (McEwen and Stellar, Arch. Int. Med. 1993; 153: 2093.).

Allostatic load can lead to disease over long periods.

Types of allostatic load include:

(1) frequent activation of allostatic systems;

(2) failure to shut off allostatic activity after stress;

(3) inadequate response of allostatic systems leading to elevated activity of other, normally counter-regulated allostatic systems after stress.

Examples will be given for each type of allostatic load from research pertaining to autonomic, CNS, neuroendocrine, and immune system activity.

The relationship of allostatic load to genetic and developmental predispositions to disease is also considered.

[2] Abstract

[3] Adaptation [of the organism] in the face of potentially stressful challenges involves activation of neural, neuroendocrine and neuroendocrine-immune mechanisms.

[4] This has been called "allostasis" or "stability through change" by Sterling and Eyer (Fisher S., Reason J. (eds): Handbook of Life Stress, Cognition and Health. J. Wiley Ltd. 1988, p. 631), and allostasis is an essential component of maintaining homeostasis.

[5] When these adaptive systems are turned on and turned off again efficiently and not too frequently, the body is able to cope effectively with challenges that it might not otherwise survive.

[6] However, there are a number of circumstances in which allostatic systems may either be overstimulated or not perform normally, and this condition has been termed "allostatic load" or the price of adaptation (McEwen and Stellar, Arch. Int. Med. 1993; 153: 2093.).

[7] Allostatic load can lead to disease over long periods.

[8] Types of allostatic load include:

[9] (1) frequent activation of allostatic systems;

[10] (2) failure to shut off allostatic activity after stress;

[11] (3) inadequate response of allostatic systems leading to elevated activity of other, normally counter-regulated allostatic systems after stress.

[12] Examples will be given for each type of allostatic load from research pertaining to autonomic, CNS, neuroendocrine, and immune system activity.

[13] The relationship of allostatic load to genetic and developmental predispositions to disease is also considered.

[sterling1988-2] Sterling P. Eyer J. (1998) Allostasis: A New Paradigm to Explain Arousal Pathology. In: Handbook of life stress, cognition, and health. Eds., Shirley Fisher and James Reason. Chichester: Wiley. ISBN 0471912697

[mcewen1993-3] 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.

[16] Abstract:

[17] 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.

[18] DATA SOURCES: Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE.

[19] DATA EXTRACTION: Independent extraction and cross-referencing by us.

[20] 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]

[21] 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.

[mcewen&seeman-4] Bruce McEwen and Teresa Seeman in collaboration with the Allostatic Load Working Group. (1999) Allostatic Load and Allostasis.

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Allostasis and allostatic load