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Allostatic Load and Allostasis

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Behavioral and Social research study Program

National institute on AgingNational institutes of Health

NIA Exploratory Workshop ~ above Allostatic Load

Washington, DC, November 29-30, 2007

Background Materials and also Statements from November 2007 Workshop Participants

Compiled November 19, 2007


Background Statement because that NIA Exploratory Workshop top top Allostatic fill Lis Nielsen, NIA/BSR Teresa Seeman, UCLA

Chapter Contents


The concept of allostatic load has served together a frame for a huge body of research on the integrative health and wellness psychology, epidemiology, and also demography that aging. The is based on the theory that there is a accumulation physiological risk associated with exposure to psychosocial stressors end the life-course. Among the attractions of such a ide is the existing human body of evidence indicating that numerous psychosocial stressors appear to have little to usual associations with multiple different organic risk factors, reflecting links to many of the known significant regulatory equipment (e.g., cardiovascular, immune, HPA, SNS) early stage empirical work based on various accumulation indices the physiological risk has detailed evidence regular with the idea that greater cumulative dysregulation is associated with considerably greater dangers for subsequent disease (cardiovascular disease), declines in physical and also cognitive functioning and also overall mortality (Seeman et al, 1997; Seeman et al, 2001; Karlamangla et al, 2002; Geronimus et al, 2006). Study has likewise documented the psychosocial conditions previously associated with higher morbidity and mortality (e.g., lower socio-economic status and poorer society engagement) are also associated with greater cumulative burdens of physiological dysregulation in multiple systems (Seeman et al, 2002; Seeman et al, 2004 Kubzansky et al 1999; Hu et al, 2006). Cumulative indices the allostatic fill have likewise been positively associated to procedures of psychosocial anxiety in young teenagers (Evans et al, 2007) and also symptoms of post-traumatic stress disorder (PTSD) in mother of pediatric cancer survivors (Glover et al, 2006) and also adverse perinatal outcomes (Shannon et al, 2007).

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Workshop Goals

Important inquiries remain, however, about the conceptualization and operationalization of allostatic load as well as the overall utility that the concept in initiatives to far better understand trajectories of health and aging. The Behavioral and also Social Research regime (BSR) in ~ the nationwide Institute on Aging looks for to development research ~ above biopsychosocial pathways of resilience and also vulnerability to so late life disease through a workshop on theoretical and methodological problems surrounding the principles of allostatic load and cumulative physiological risk much more generally. The goal of the 2007 workshop is to carry together scientists from diverse techniques who share an interest in knowledge stress-health relationship from a life-course perspective, however who might differ in your approaches and also commitment come the allostatic pack model. We conceive of this group as a collaborative team whose interests are concentrated on what is required to advancement behavioral and social research study on aging within this subject area.

The calculation of this workshop should include widely dispersed publications that will serve as referrals for created and new researchers in the fields of behavioral and also social aging research in addition to recommendations about needed study to advancement our understanding of the organic pathways v which our life experiences influence on health and aging.

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Aging and allostatic load

Aging is linked with raised risk because that most develops of disability and also chronic disease, through the majority of older adults suffering two or an ext chronic conditions by the moment they with old period (Singer, Ryff, & Seeman, 2004). It has been hypothesized that cumulative lifetime exposure to social, emotional or environmental stressors boosts the threat of many age-related health difficulties by disrupting the physiological regulatory systems that mediate the stress response. Allostatic load has been placed forth together a version for how features of the psychosocial setting �get under the skin� and give increase to disease. The design (based top top the principle of biological adaptation come duress first proposed by Cannon (1932) and Selye (1956, 1974), emerged by McEwen and colleagues (McEwen and also Stellar, 1993; McEwen, 1998; McEwen and Seeman, 1999; and elaborated most recently in a volume edited by Jay Schulkin, 2004) proposes the a crucial mediator of boosting risk for an illness is the dysregulation of solution designed to balance the organism�s responses to environmental demands. Exposure to stress and anxiety elicits adaptive physiological responses in regulation systems including the hypothalamic pituitary axis (HPA), the sorry (SNS) and also parasympathetic (PNS) branches that the autonomic concerned system, and the cardiovascular and also immune systems. Allostasis (related to homeostasis) is the adaptive maintain of vitality in these solution via neuromodulation of engine states and also behaviors in response to an altering environmental circumstances. Allostatic load refers come the cumulative biological wear and also tear the can an outcome from excessive cycles of solution (i.e., too frequent and/or of inappropriate duration or scope) in these solution as they look for to maintain allostasis in the face of ecological challenge. According to the theory, as these systems come to be taxed and dysregulated, they begin to exhibit discrepancies in the primary neural mediators the the stress and anxiety response, such together glucocorticoids, catecholamines and proinflammatory cytokines. Dysregulation is confirmed in both basal level of device parameters - including circulating baseline levels of these hormones - and also in trends of dynamic an answer to stimuli. Chronic dysregulation is thought to confer accumulation physiological danger for disease and disability by causing damages to organization and major organ systems.

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Mechanisms and also measurement

At the level of mechanisms, that is famous that a hold of stressors � social and environmental elicitors of negative emotions, pathogens, physical challenges - lead to activations that physiological equipment designed to preserve balance (McEwen & Stellar, 1993). Moreover, accumulating proof supports the concept that stressors such as reduced socioeconomic status, at an early stage exposure come abuse, diminished social support, and also conflictual relationships (to name a few) are linked with increased threats for bad mental and physical wellness outcomes and mortality (Taylor, Repetti, & Seeman, 1997).

As an initial effort to operationalize the ide of allostatic load, Seeman, McEwen, and also colleagues provided existing data indigenous the MacArthur study of successful Aging to develop an initial measure of allostatic pack that represented a straightforward count the the number of vital biomarkers of cardiovascular, immune, and also HPA axis dysfunction on which an separation, personal, instance is in the highest risk quartile. The biomarkers contained in this an introduction measure were obtained from available data native the MacArthur examine that represented parameters of major regulatory systems with known or hypothesized web links to various significant health endpoints, consisting of disease, disability and also mortality (Seeman et al, 1997). Population-based inspection research, where much attention has concentrated on identifying organic markers that index risk for so late life an illness outcomes, has provided evidence that higher levels that allostatic fill are associated with enhanced morbidity and also mortality (Seeman et al, 1997; 2001) and that greater educational attainment and better social relationship are linked with lower levels of allostatic fill (Seeman et al, 2002; 2004). Different measurement models for allostatic pack (canonical correlation, recursive partitioning) have yielded findings continuous with previously approaches (Karlamangla et al, 2002; Gruenewald et al, 2006).

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State that the evidence

Current evidence, however, walk not provide definitive support for the propose relationships between psychosocial stressors and also dysregulation of organic systems sustaining allostasis. Many organic regulatory systems show up to present age-related increase in level of dysregulation, but age related changes are no uniform in ~ populations. That is unknown what determines who exhibits such age-related changes and also who manages to stop them despite a farming body of evidence points to socio-economic distinctions in prices of build-up (those of reduced SES exhibiting earlier and larger accumulations the AL; Crimmins et al, 2003; Seeman et al, 2004; Geronimus et al, 2006; Seeman et al, in press) and also differences relating to socially supportive attributes of one�s relationships through others (Singer & Ryff, 1999; Seeman et al, 2002). In addition, there is a cultivation body the correlational evidence indicating that individuals vary in their response to stressors based on differences in personality, coping and also emotional regulatory styles, and social and cultural environments (e.g., Ryff, Singer, & Love, 2004). For this reason some individuals seem resilient to conditions of aging and present v a file of positive health and well-being the may defend stress regulatory equipment from dysregulation. Concerns remain as to whether some world are gene disposed to higher resilience to stress, or even if it is life-style, psychosocial, and also socioeconomic factors are responsible because that these differences.

Not all scientists are convinced that organic measures have added significantly to our knowledge of risk and also resilience pathways. Some have actually questioned whether biomarkers actually measure, together hypothesized, the mediators the psychosocial impacts on health. Even amongst social and behavioral researchers committed to use biomarkers and physiological actions in your research, over there is one awareness of significant gaps in the theoretical model and also needs because that refinement that methodologies and analytical strategies. Much more needs to it is in known around which biomarkers (and/or combine of biomarkers) room most helpful in predicting wellness outcomes in enlarge age, and which psychosocial factors are the vital predictors of change in these biomarkers end time. These researchers proceed to wrest through measurement issues around �allostatic load� as they strive to save apace that findings arising from the biological literature on disease markers and key indicators the age-related physiological decline. The present workshop will focus on this pressing theoretical and measure up issues.

While the allostatic pack model places emphasis on the organic pathways with which psychosocial components have their impacts on health and wellness outcomes, it should be emphasized that the totally integrative biopsychosocial version is recursive, with numerous and facility hypothesized bidirectional causal pathways. Real progression in integrative physiology calls for the advancement of brand-new analytical methods that allow exploration of this multiple causative links, as well as advances in measurement at the level of the physics environment, the society context, the mental subject, and the biological markers and mechanisms basic health and also disease.

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Topics to be addressed in the workshop and also papers

Conceptual and also theoretical issues

Allostatic pack is both a theoretical construct and a measure of accumulation wear and tear ~ above physiological symptoms due to chronic stress. As a theoretical construct, the is a preliminary effort to formulate the relationship in between environmental stressors and also disease, by hypothesizing mechanisms by which multiple kinds of stressors confer risk concurrently in many physiological equipment (Singer & Ryff, 2001). Necessary questions surrounding the ide of allostatic load problem (1) the partnership of varied research result to the all at once theory, (2) the distinction between major mediators of condition and secondary outcomes, (3) the links in between allostatic load and specific condition outcomes, i.e., go allostatic fill represents a distinctive �syndrome� or very early stage on the pathway come multiple diseases, and also (4) whether there are various allostatic pack pathways, and if so, just how do these differ indigenous unique disease pathways?

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Methodological: measure of allostatic load

Which biomarkers? The currently obtainable assortment that biomarkers for measuring materials of allostatic load is extensive and includes: anthropometric, cardiovascular and metabolic measures, inflammation markers, procedures of HPA axis and SNS activity, actions of renal function, lung function, bone density, immune functioning, antioxidants, hereditary markers, and adiposity. One of the aims of this workshop is to encourage researchers to move past examination of exactly how a single psychosocial aspect influences a solitary biological device or health outcome and toward a much more comprehensive view of the miscellaneous profiles of dysregulation that might develop. Greater attention needs to be paid to major mediators the can affect multiple other regulatory equipment (e.g. Cortisol, inflammation cytokines, catecholamines) as well as to anabolic hormones that may mediate resilience (e.g. Igf-1, DHEA, testosterone).

Multi-system approaches. the is inherent in the hypothesis that a life time of exposure come stressors of varied origin will have cumulative results on multiple organic systems the we must be interested in readjust in multiple equipment over time. A limitation of most prior occupational on allostatic pack model is the it has been based upon measures of biomarkers from just one suggest in time. However, if chronic tension disrupts allostatic pack component solution sequentially, it might be an ext appropriate come look very first at beforehand alterations in neuroendocrine systems, later at elevations in inflammatory markers, and even later on at markers of metabolic syndrome. One an essential question to be addressed by the workshop will be what the ideal models room for looking in ~ this. Longitudinal measurements of biomarkers may provide vital information around the pathways of accumulation dysregulation that result in disease.

Biological aging as the background. The affect of chronic and also daily stressors top top regulatory solution occurs versus a lift of typical age-related decreases in immune function, and also the communication of these determinants may pose added health risks. Enlarge adults appear to display even better immunological impairments associated with stress and anxiety or depression than young adults, making determinants that are associated with greater stress potentially more lethal come the yonsei (Kiecolt-Glaser & Glaser, 2002). It will certainly be essential to understand how accumulation of allostatic pack interacts v �normal� age-related dysregulation in each of the solution that modulate stress responses.

Multiple level of analysis. Additionally, this workshop should check out research tactics that allow the check of these relationships at multiple levels (from an ext molecular up through much more macro-level assessments of social conditions) by supplying models for trying out pathways between levels and examples of successful research that has adopted this approach. Importantly, measure up of biological dysregulation calls for both an check of distinctions in basal activity as fine as and also examination of mechanism dynamics in an answer to challenge.

Measures of reactivity in systems. While procedures of tension reactivity often tend to it is in of higher cost, they room ultimately necessary for experimentation the principle of allostatic load, since patterns the reaction in this systems might be the earliest signs of dysregulation. Research is needed to clarify whereby in mechanism dynamics dysregulations space most obvious or most consequential, e.g. In an answer versus recovery parameters. A variety of an obstacle paradigms exist for examining the effects of tension on regulation systems, including wound healing, inoculation response, and social and cognitive tension paradigms design for use with actions of psychophysiological reactivity. What perform the result from these sorts of researches tell us about individual differences in anxiety responsivity, links between dysregulation and details psychosocial factors and also health outcomes, and also relationships in between dysregulation top top the assorted measures? emotionally reactivity theatre a pivotal duty in the solution to stress. Just how much of emotional reactivity is biologically, genetically or environmentally determined? What room the present measures of emotionally reactivity to stress, and what is known about how these develop and vary end the life course?

Lab-survey linkages. Importantly, links need to it is in forged in between studies that focus on detailed evaluations of organic mechanisms in the activities or field and population-based research studies with higher generalizability the don�t permit for such thorough physiological assessment. Offered the complementing staminas of laboratory and also ambulatory research study it is now feasible and fruitful to extend traditional laboratory studies with endure sampling methodologies and corresponding ambulatory physiological, behavioral, and also endocrinological assessments. Such studies would administer insight into the opportunity that dysregulation is originally most apparent in patterns of response, while more basal task is much less easily impacted and might only show age-related changes reasonably late in the procedure of development of condition and dysregulation. Participants are urged to envision ideal research designs the would carry out insights on transforms in regulatory systems and their association with past and also current psychosocial factors. The workshop should carry out a snapshot of state the the art study in this area, and suggest to potentials for and also obstacles to renovations in research designs.

Genetics. as we learn more about the ingredient of the genome and also mechanisms regulating gene expression, and also as inexpensive methods for measuring DNA build rapidly, it will be possible to combine genetic data with much more comprehensive models that encompass information on behavioral, social and other attributes of individuals, and enabling study the gene-environment interaction. Additionally, there is an arising interest in examining the hereditary basis because that individual distinctions in response to or susceptibility to stress, a much more nuanced evaluation of the details psychosocial phenotypes the play a role in health and wellness outcomes and also the basic genetic and also gene by atmosphere interactions that determine their expression.

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Additional measurement issues include:

What selection of currently obtainable biomarkers are many predictive of certain health outcomes, and which are indicative of health and wellness status no revealed through self-report?

What are the criteria through which new biomarkers must be evaluated because that inclusion in study on cumulative physiological risk?

What cumulative steps of allostatic load present most promise? how are they ideal analyzed? just how should steps be combined to best clarify procedures of change in health?

Do different biomarkers mean different things at various times in life, and if so, which actions are meaningful at i beg your pardon ages?

For various regulatory solution that change over time, just how does one model the interrelated effects of these equipment on outcomes?

What requirements to be done to clear up the links between primary mediators and second outcomes (e.g., inflammation, antioxidants and also hormones as primary, bone health and also hypertension together secondary)?

How do measures of allostatic pack relate to indices such together Metabolic Syndrome and the Framingham hazard Score?

How trustworthy are currently biomarker actions of accumulation risk? how reliable are procedures of the individual contents of cumulative hazard scores?

Relatedly, explorations that variability in main mediators with time are needed, as tiny is known about this. Is variability on certain measures itself an outcome of potential significance? Are people who display greater variability at greater risk than those that are relatively stable on measures?

Are different physiological systems more or less vulnerable to different varieties of psychosocial stressors (financial, social isolation, interpersonal conflict) and also what room the effects for disease outcomes?

Is there much more than one allostatic fill profile, e.g. Hypocortisolism vs. Hypercortisolism; hypercholesterolism vs. Hypocholesterolism, and do the health after-effects of this profiles readjust with age?

What is the relative importance of beforehand life exposures to stress, versus later on life exposures? space there courses of no return, critical periods? Are impacts of stress reversible? does this vary by life period exposure?

How do profiles that allostatic fill differ by ethnicity and also gender?

How have to we account for individual differences in responses come stress?

What type of studies could be envisioned that would certainly permit both pre- and also post-stress organic measures, and measures of separation, personal, instance difference characteristics that might modify fads of physiological response?

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Cannon, W.B. (1932). The Wisdom the the Body. Brand-new York: Norton. Cited in Schulkin J. Allostasis, Homeostasis, and also the costs of Physiological Adaptation. Oxford: Cambridge college Press, 2004

Crimmins EM, Johnson M, Hayward M, Seeman T. Age differences in allostatic load: an index of physiological dysregulation. Experimental Gerontology. July 38: 731-734, 2003.

Evans GW, Kim P, Ting AH, Tesher HB, Shannis D. Cumulative risk, maternal responsiveness and also allostatic load among young adolescents. Dev Psychol 43:341-51, 2007.

Geronimus A.T., Hicken, M., Keene, D., Bound, J. "Weathering" and also age patterns of allostatic pack scores among Blacks and Whites in the joined States. AJPH 96, 826-33, 2006

Glover DA, Stuber M, Poland RE. Allostatic load in ladies with and without PTSD symptoms. Psychiatry, 69:191-203, 2006.

Gruenewald TL, Seeman TE, Ryff CD, Karlamangla AS, Singer BH. Combine of Biomarkers Predictive of later on Life Mortality. Proceedings that the national Academy the Sciences, 103(38):14158-14163, 2006

Hu P, Wagle N, Goldman N, Weinstein M, Seeman TE. The Associations in between Socioeconomic Status, Allostatic Load and also Measures of wellness in enlarge Taiwanese Persons: Taiwan society Environment and Biomarkers of Aging Study. Newspaper of Biosocial Science, Oct 20;:1-12, 2006. .

Karlamangla, A.S., B.H. Singer, B.S. McEwen, J.W. Rowe, and Seeman TE. Allostatic lead together a predictor of practical decline: MacArthur researches of effective Aging. Journal of Clinical Epidemiology, Vol 55, No. 7, 696-710, July 2002.

Kiecolt-Glaser JK, Glaser R. Depression and immune function: main pathways come morbidity and also mortality. Newspaper of Psychosomatic Research, 2002 Oct;53(4):873-6.

Kubzansky LD, Kawachi I, Sparrow D. Socioeconomic status, hostility, and risk factor clustering in the Normative Aging Study: any aid from the ide of allostatic load? Annals of behavior Medicine 1999;21(4):330-8

McEwen BS. Protective and also damaging impacts of stress and anxiety mediators. Brand-new England journal of medication 1998;338:171-9

McEwen BS, Seeman TE. Protective and also damaging results of mediators that stress. In Socioeconomic Status and also Health in industrial Nations: Social, Psychological and also Biological Pathways, Adler NE, Marmot M, McEwen BS (eds), NY: NY academic of Sciences, 896:30-47, 1999.

McEwen BS, stellar E. Stress and also the individual: mechanisms resulting in disease. Archives of inner Medicine 1993;153:2093-101.

Ryff CD & Singer B (eds), Emotion, society Relationships and Health. Brand-new York: Oxford Press, pp189-209, 2001.

Ryff CD, Singer BH, Dienberg Love G. Confident health: Connecting well-being v biology. Philos infectious diseases world fashion R Soc lond B Biol Sci. 359:1383-94, 2004.

Schulkin J. Allostasis, Homeostasis, and the prices of Physiological Adaptation. Oxford: Cambridge university Press, 2004

Seeman TE, Singer B, Horwitz R, McEwen BS. "The Price that Adaptation --Allostatic pack & Its wellness Consequences: MacArthur research studies of successful Aging" Archives of internal Medicine 157:2259-2268, 1997.

Seeman TE, Singer B, Rowe J, McEwen B. Exploring a brand-new concept that cumulative organic risk -- Allostatic pack & its health consequences: MacArthur studies of effective Aging. Proc Nat Acad Sci USA 98(8): 4770-4775, 2001.

Seeman TE, Singer B, Ryff C Levy-Storms L. Psychosocial factors and also the advance of allostatic load. Psychosomatic medication 64:395-406, May/June 2002.

Seeman TE, Crimmins E, Bucur A., Huang MH, Singer B, Bucur A, Gruenewald T, Berkman LF, Reuben DB. Cumulative organic Risk and also Socio-Economic distinctions in Mortality: MacArthur researches of effective Aging. Soc Sci & Med 58, 1985-1997, 2004

Seeman TE, Merkin S, Crimmins E, Koretz B, Charrette S, Karlamangla A. Education, Income and Ethnic distinctions in Cumulative biological Risk file in a national Sample of us Adults: NHANES III; social Science and also Medicine, in press.

Selye, H. (1956). The stress and anxiety of Life. New York: McGraw-Hill. Quote in Schulkin J. Allostasis, Homeostasis, and also the costs of Physiological Adaptation. Oxford: Cambridge university Press, 2004

Selye, H. (1974). Tension without Distres. Brand-new York: brand-new American Library. Quote in Schulkin J. Allostasis, Homeostasis, and the prices of Physiological Adaptation. Oxford: Cambridge college Press, 2004

Shannon M, King TL, Kennedy HP. Allostasis: a theoretical structure for understanding and analyzing prenatal wellness outcomes. J. Obstet Gynecol Neonatal Nurs. 36:125-134, 2007.

Singer B, Ryff C, Seeman TE. Operationalizing Allostatic Load. In Allostasis, Homeostasis, and also the expense of Physiological Adaptation.

See more: Does Gatorade Keep You Awake And Energetic Before Exam? If Yes Then How?

J. Schulkin (ed). Pp 113-149, 2004

Singer B, Ryff CD. Hierarchies of life histories and associated wellness risks. Annals of new York Academy of sciences 1999;896:96-115.

Taylor SE, Repetti RL, Seeman TE. "What is one Unhealthy Environment and How walk It obtain Under the Skin?" annual Review of Psychology, 48:411-47, 1997

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Charge come Participants in the NIA Workshop ~ above Allostatic Load

In preparation for the upcoming NIA Exploratory Workshop on Allostatic Load, participants were asked come prepare a short (2-4 pages) statements outlining their views on just how research ~ above allostatic load and also the research of cumulative risk an ext generally have the right to be most fruitfully progressed in the behavioral and social sciences. These statements space intended to set the structures for dialogue, at the workshop, on research and resource needs for achieving this goal.

As explained in the foregoing lift document, there are a number of theoretical and methodological concerns that could be addressed at the workshop. Participants were asked to market creative, well-informed entry on whereby the arising research opportunities and needs lie in ~ thier own and related fields.

Participants to be asked to think about the adhering to when preparing your statements:

How has actually the principle of allostatic load had actually a positive (or negative) affect on work in your field? room there an ext valuable alternate approaches come the examine of cumulative physiological risk, and if so, what are they and also what is their loved one advantage? What can be excellent to make this concept much more valuable to study on social and behavioral factors in aging? What are the most an essential measurement issues, in your view? are there certain data requirements for addressing these questions? What would be the most essential "next steps" in moving research top top allostatic load, or accumulation physiological risk more generally, forward?