Regular articleThe concept of allostasis in biology and biomedicine
Introduction
Modern biology provides a framework not only for understanding how the interplay of genes and environment produces individual characteristics, and how these individuals interact in social groups and with other species, but also for understanding how these interactions lead to pathophysiology and disease. For example, knowledge of how the life cycles of organisms are integrated and controlled in the natural world will allow us to assess the effects upon ecosystems of global climate change, disturbance by humans, and endocrine disrupters. Of equal importance is a need to use basic biological frameworks in human society to conceptualize and measure the cumulative impact of social status, income, education, working and living environments, lifestyle, health-related behaviors, and stressful life experiences on physical and mental health.
The daily routines of animals and humans alike include nutritional inputs to maintain normal activities and to anticipate additional requirements (e.g., breeding, migrating, acclimating to cold and heat, etc.) during the day–night cycle and the seasons. These homeostatic mechanisms, including functional and structural changes in brain and body, allow the individual to maintain physiological and behavioral stability despite fluctuating environmental conditions. Superimposed on this “predictable” life cycle are facultative physiological and behavioral responses to unpredictable events that have the potential to be stressors. These responses require extra energy procured from the environment and/or from endogenous stores of fat, glycogen, and protein. Moreover, the ability of an individual to maintain such emergency responses depends upon other factors such as parasite load, diseases, social status, permanent injury, pollution, etc. These can lead to permanent additional “costs” that potentially provide a “handicap” in the face of environmental change, unpredictable events, etc.
Historically, within both the basic biological and biomedical sciences, the concepts of stress and homeostasis have been used in ambiguous ways that obfuscate a number of important aspects of the impact of experience and genes on life cycles in general, and health and disease in particular. The energy required to fuel daily and seasonal routines includes major life history stages such as breeding, unpredictable events that can lead to stress, and the permanent handicaps accrued from disease, injury, etc. These form a continuum with important transitional points that determine whether the individual can cope or triggers facultative physiological and behavioral responses designed to reduce costs. Failure to do either results in symptoms of what we call “allostatic overload,” as discussed below.
Our goal here is to propose the inclusion of four terms, “allostasis,” “allostatic state,” “allostatic load,” and “allostatic overload” in a basic framework for the organization and management of life cycles. These terms are offered as organizing principles for understanding the management of life cycles in diverse habitats and varying degrees of unpredictability in basic biology. They also include the influence of genetic risk factors, early life events, lifestyle and health-related behaviors and stressful experiences, including social conflict and social hierarchies, on the processes of physiological adaptation and the exacerbation of disease.
The process of allostasis that leads adaptation/acclimation of the organism in the short run underlies all of what we shall discuss. We will explore how costs to the body (referred to as allostatic load) can eventually result in allostatic overload, i.e., the balance between energy expenditure and energy input. We understand fully that this is a simplistic approach and many other nutritional components (essential fatty acids and amino acids, minerals, etc.) are important. These indeed could also be modeled, but here we use the term “energy” in a very general sense that encompasses all potentially limiting resources. Moreover, we focus on glucocorticosteroids as hormonal mediators that reflect how the individual responds to the challenges imposed by the external world as well as by the internal environment. We do so in full recognition of the fact that glucocorticosteroids are only one of many interconnected hormonal mediators and that a full description of what we are outlining will require inclusion of these mediators as well.
First, we consider situations in which energy available to the organism is exceeded by demands of the environment. Second, we consider situations when energy available to the individual is not exceeded, but other factors such as social competition and conflict become paramount. Before elaborating on these ideas, we need to define some terminology.
Section snippets
Homeostasis
Homeostasis is the stability of physiological systems that maintain life, used here to apply strictly to a limited number of systems such as pH, body temperature, glucose levels, and oxygen tension that are truly essential for life and are therefore maintained within a range optimal for the current life history stage.
Allostasis
Allostasis is achieving stability through change. This is a process that supports homeostasis, i.e., those physiological parameters essential for life defined above, as
What do we mean by “stress”?
Stress is often defined as a threat, real or implied, to homeostasis. In common usage, stress usually refers to an event or succession of events that cause a response, often in the form of “distress” but also, in some cases, referring to a challenge that leads to a feeling of exhilaration, as in “good” stress. But, the term “stress” is full of ambiguities. It is often used to mean the event (stressor) or, sometimes, the response (stress response). Furthermore, it is frequently used in the
What are some examples of allostasis?
Sterling and Eyer (1988) used variations in blood pressure as an example: in the morning, blood pressure rises when we get out of bed and blood flow is maintained to the brain when we stand up in order to keep us conscious. This type of allostasis helps to maintain oxygen tension in the brain. There are other examples: catecholamine and glucocorticosteroid elevations during physical activity mobilize and replenish, respectively, energy stores needed for brain and body function under challenge.
Protection vs damage
From the standpoint of survival and health of the individual, the most important feature of mediators associated with allostasis is that they have protective effects in the short run. However, they can have damaging effects over longer time intervals if there are many adverse life events or if hormone secretion is dysregulated as in a sustained allostatic state that leads to allostatic overload (McEwen, 1998). In contrast to Selye (1956), this view holds that mediators of allostasis have a
Allostasis as a concept to unify approaches to perturbations of the environment in biological and biomedical contexts
There are potentially two complementary views of allostasis, allostatic states, allostatic load, and allostatic overload. One involves how organisms in their natural environment search for basic needs such as food and shelter, thereby enhancing overall fitness. In these cases individuals must orchestrate daily and seasonal needs in relation to environmental conditions and social status, as well as deal with unpredictable events in the environment. Failure to deal with these problems results in
Allostatic load and type 1 overload to cope with unpredictable environmental events that threaten food availability and quality of shelter—mechanisms to avoid and resist stress
All organisms must adjust their physiology, morphology, and behavior in response to changing environments — physical and social, predictable and unpredictable. This allows an individual to avoid or resist the potential for stress Sapolsky et al 2000, Wingfield et al 1998, Wingfield and Romero 2000. The rapid behavioral and physiological changes in response to perturbations have been collectively called the “emergency” life history stage, which serves to enhance lifetime fitness (Wingfield et
Allostatic load and type 2 overload—what happens when competitive social structure predominates over food and shelter as a source of challenge?
The distinction between views of Type 1 allostatic overload versus allostatic load in some forms of human disease is that increasing energy requirement is the drive leading eventually to allostatic overload when negative energy balance is reached (Ee + Ei + Eo > Eg; Fig. 1, Fig. 2). Unless the emergency life history stage reduces allostatic load (Fig. 3) to regain positive energy balance (Ee + Ei + Eo < Eg), then cumulative effects become pathological. In modern human society, we see positive
Type 2 allostatic load—a human perspective
The situations depicted in Fig. 4 are an attempt to put into an energy model the conditions that exist in the modern industrialized world with its social hierarchies and differing degrees of inequality. Modern Western society is characterized not by hunger and the search for basic creature comforts as by complex social structures. These involve living and working environments that vary in quality, variable access to recreation, and the existence of mass communications with a variety of messages
Conclusions
Most vertebrate organisms have regular patterns and routines that involve obtaining food and carrying out life history stages such as breeding, migrating, molting, hibernating, etc. These life history stages occur in set sequences on a time scale of about 1 year. Each has energetic requirements that vary according to demand. Often, life history stages such as reproduction and migration are energetically demanding, whereas others rely on stored energy only (hibernation). The annual sequence of
Acknowledgements
J.C.W. is grateful for several grants from the Division of Integrated Biology and Neuroscience, and the Office of Polar Programs, National Science Foundation. He also acknowledges a John Simon Guggenheim Fellowship, a Benjamin Meaker Fellowship (University of Bristol, UK), and a Russell F. Stark University Professorship (University of Washington). B.Mc. acknowledges the intellectual support from colleagues in the MacArthur Research Network for Socioeconomic Status and Health, Nancy Adler, UCSF,
References (83)
- et al.
Socioeconomic factors, perceived control and self-reported health in Russia. A cross-sectional survey
Soc. Sci. Med.
(1998) - et al.
Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The adverse childhood experiences (ACE) study
Am. J. Prev. Med.
(1998) - et al.
Corticosterone, foraging behavior, and metabolism in dark-eyed juncos
Junco hyemalis. Gen. Comp. Endocrinol.
(1990) - et al.
Corticosterone and nocturnal torpor in the rufous hummingbird (Selasphorus rufus)
Gen. Comp. Endocrinol.
(2000) - et al.
Noninvasive methods for measuring and manipulating corticosterone in hummingbirds
Gen. Comp. Endocrinol.
(2000) - et al.
Drug addiction, dysregulation of reward, and allostasis
Neuropsychopharmacology
(2001) - et al.
Health inequalities among British civil servantsThe Whitehall II study
Lancet
(1991) Allostasis and allostatic loadimplications for neuropsychopharmacology
Neuropsychopharmacology
(2000)- et al.
Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression
Biol. Psychiat.
(1999)
Glucocorticoids and the regulation of memory consolidation
Psychoneuroendocrinology
Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement
Neuroscience
Effects of corticosterone on territorial behavior of free-living song sparrows, Melospiza melodia
Horm. Behav.
Socioeconomic inequalities in healthno easy solution
J. Am. Med. Assoc.
Socioeconomic status and healththe challenge of the gradient
Am. Psychol.
Regulation of nutrient partitioning during lactationhomeostasis and homeorhesis revisited,
Diabetes-associated sustained activation of the transcription factor nuclear factor-κB
Diabetes
East–West mortality divide and its potential explanationsproposed research agenda
Br. Med. J.
Possible connections between stress, diabetes, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis
Clin. Sci.
Socioeconomic status
Advances in dietary management of obesity in dogs and cats
J. Nutr.
Beta-adrenergic activation and memory for emotional events
Nature
The wisdom of the body
Physiol. Rev.
Do Lemmings Commit Suicide? Beautiful Hypotheses and Ugly Facts
Social ties and susceptibility to the common cold
J. Am. Med. Assoc.
Epidemiology of musculoskeletal impairments and associated disability
Am. J. Public Health
Association of breast cancer and cervical cancer incidences with income and education among whites and blacks
J. Natl. Cancer Inst.
Enhancing versus suppressive effects of stress hormones on skin immune function
Proc. Natl. Acad. Sci. USA
Socioeconomic status and psychiatric disordersthe causation-selection issue
Science
Hormonal and behavioral responses to food and water deprivation in a lizard (Sceloporus occidentalis): implications for assessing stress in a natural population
J. Herpetol.
External and internal influences on indices of physiological stress. II. Seasonal and size-related variation in blood composition of free-living lizards during drought
J. Exp. Zool.
Hormonal alterations and reproductive inhibition in lizards, Sceloporus occidentalis infected with the malarial parasite, Plasmodium mexicanum.
Physiol. Zool.
External and internal influences on indices of Physiological stress. I. Seasonal and population variation in adrenocortical secretion of free-living lizards, Sceloporus occidentalis
J. Exp. Zool.
Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosispopulation based study
Br. Med. J.
Vital exhaustion, anger expression, and pituitary and adrenocortical hormonesimplications for the insulin resistance syndrome
Arterioscler. Thromb. Vasc. Biol.
Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United Statesresults from the National Comorbidity Survey
Arch. Gen. Psychiat.
The adrenocortical stress response of black-legged kittiwake chicks in relation to dietary restrictions
J. Comp. Physiol. B
Relationship of blood coagulation and fibrinolysis to vital exhaustation
Psychosom. Med.
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