Email: TSeeman@mednet.ucla.edu Anneliese Hahn, M.S.
Research Program Analyst
Background Statement for NIA Exploratory Workshop on Allostatic Load
Lis Nielsen, NIA/BSR
Teresa Seeman, UCLA
The concept of allostatic load has served as a framework for a large body of research on the integrative health psychology, epidemiology, and demography of aging. It is based on the hypothesis that there is a cumulative physiological risk associated with exposure to psychosocial stressors over the life-course. Among the attractions of such a concept is the existing body of evidence indicating that many psychosocial stressors appear to have small to modest associations with multiple different biological risk factors, reflecting links to most of the known major regulatory systems (e.g., cardiovascular, immune, HPA, SNS) Initial empirical work based on various cumulative indices of physiological risk has provided evidence consistent with the idea that greater cumulative dysregulation is associated with significantly greater risks for subsequent disease (cardiovascular disease), declines in physical and cognitive functioning and overall mortality (Seeman et al, 1997; Seeman et al, 2001; Karlamangla et al, 2002; Geronimus et al, 2006). Research has also documented that psychosocial conditions previously associated with greater morbidity and mortality (e.g., lower socio-economic status and poorer social 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 of allostatic load have also been positively related to measures of psychosocial stress in young adolescents (Evans et al, 2007) as well as symptoms of post-traumatic stress disorder (PTSD) in mothers of pediatric cancer survivors (Glover et al, 2006) and adverse perinatal outcomes (Shannon et al, 2007).
Important questions remain, however, regarding the conceptualization and operationalization of allostatic load as well as the overall utility of the concept in efforts to better understand trajectories of health and aging. The Behavioral and Social Research Program (BSR) at the National Institute on Aging seeks to advance research on biopsychosocial pathways of resilience and vulnerability to late life disease through a workshop on conceptual and methodological issues surrounding the concepts of allostatic load and cumulative physiological risk more generally. The goal of the 2007 workshop is to bring together scientists from diverse disciplines who share an interest in understanding stress-health relationships from a life-course perspective, but who may differ in their approaches and commitment to the allostatic load model. We conceive of this group as a collaborative team whose interests are focused on what is needed to advance behavioral and social research on aging within this topic area.
The output of this workshop should include widely distributed publications that will serve as references for established and new researchers in the fields of behavioral and social aging research along with recommendations regarding needed research to advance our understanding of the biological pathways through which our life experiences impact on health and aging.
Aging and allostatic load Aging is associated with increased risk for most forms of disability and chronic disease, with the majority of older adults experiencing two or more chronic conditions by the time they reach old age (Singer, Ryff, & Seeman, 2004). It has been hypothesized that cumulative lifetime exposure to social, psychological or environmental stressors increases the risk of multiple age-related health problems by disrupting the physiological regulatory systems that mediate the stress response. Allostatic load has been put forth as a model for how features of the psychosocial environment “get under the skin” and give rise to disease. The model (based on the concept of biological adaptation to duress first proposed by Cannon (1932) and Selye (1956, 1974), developed by McEwen and colleagues (McEwen and Stellar, 1993; McEwen, 1998; McEwen and Seeman, 1999; and elaborated most recently in a volume edited by Jay Schulkin, 2004) proposes that a key mediator of increasing risk for disease is the dysregulation of systems designed to balance the organism’s responses to environmental demands. Exposure to stress elicits adaptive physiological responses in regulatory systems including the hypothalamic pituitary axis (HPA), the sympathetic (SNS) and parasympathetic (PNS) branches of the autonomic nervous system, and the cardiovascular and immune systems. Allostasis (related to homeostasis) is the adaptive maintenance of vitality in these systems via neuromodulation of motive states and behaviors in response to changing environmental circumstances. Allostatic load refers to the cumulative biological wear and tear that can result from excessive cycles of response (i.e., too frequent and/or of inappropriate duration or scope) in these systems as they seek to maintain allostasis in the face of environmental challenge. According to the theory, as these systems become taxed and dysregulated, they begin to exhibit imbalances in the primary neural mediators of the stress response, such as glucocorticoids, catecholamines and proinflammatory cytokines. Dysregulation is evidenced in both basal levels of system parameters - including circulating baseline levels of these hormones - as well as in patterns of dynamic response to stimuli. Chronic dysregulation is believed to confer cumulative physiological risk for disease and disability by causing damage to tissues and major organ systems.
Mechanisms and measurement
At the level of mechanisms, it is well known that a host of stressors – social and environmental elicitors of negative emotions, pathogens, physical challenges - lead to activations of physiological systems designed to maintain balance (McEwen & Stellar, 1993). Moreover, accumulating evidence supports the notion that stressors such as lower socioeconomic status, early exposure to abuse, diminished social support, and conflictual relationships (to name a few) are associated with increased risks for poor mental and physical health outcomes and mortality (Taylor, Repetti, & Seeman, 1997).
As an initial attempt to operationalize the concept of allostatic load, Seeman, McEwen, and colleagues used existing data from the MacArthur Study of Successful Aging to develop an initial measure of allostatic load that represented a simple count of the number of critical biomarkers of cardiovascular, immune, and HPA axis dysfunction on which an individual is in the highest risk quartile. The biomarkers included in this summary measure were derived from available data from the MacArthur Study that represented parameters of major regulatory systems with known or hypothesized links to various major health endpoints, including disease, disability and mortality (Seeman et al, 1997). Population-based survey research, where much attention has focused on identifying biological markers that index risk for late life disease outcomes, has provided evidence that higher levels of allostatic load are associated with increased morbidity and mortality (Seeman et al, 1997; 2001) and that higher educational attainment and better social relationships are associated with lower levels of allostatic load (Seeman et al, 2002; 2004). Alternative measurement models for allostatic load (canonical correlation, recursive partitioning) have yielded findings consistent with earlier approaches (Karlamangla et al, 2002; Gruenewald et al, 2006).
State of the evidence
Current evidence, however, does not provide definitive support for the proposed relationships between psychosocial stressors and dysregulation of biological systems supporting allostasis. Many biological regulatory systems appear to show age-related increase in levels of dysregulation, but age related changes are not uniform within populations. It is unknown what determines who exhibits such age-related changes and who manages to avoid them though a growing body of evidence points to socio-economic differences in rates of accumulation (those of lower SES exhibiting earlier and larger accumulations of AL; Crimmins et al, 2003; Seeman et al, 2004; Geronimus et al, 2006; Seeman et al, in press) as well as differences relating to socially supportive qualities of one’s relationships with others (Singer & Ryff, 1999; Seeman et al, 2002). In addition, there is a growing body of correlational evidence indicating that individuals vary in their response to stressors based on differences in personality, coping and emotional regulatory styles, and social and cultural environments (e.g., Ryff, Singer, & Love, 2004). Thus some individuals seem resilient to diseases of aging and present with a profile of positive health and well-being that may protect stress regulatory systems from dysregulation. Questions remain as to whether some people are genetically disposed to greater resilience to stress, or whether life-style, psychosocial, and socioeconomic factors are responsible for these differences.
Not all scientists are convinced that biological measures have added significantly to our understanding of risk and resilience pathways. Some have questioned whether biomarkers actually measure, as hypothesized, the mediators of psychosocial impacts on health. Even among social and behavioral researchers committed to employing biomarkers and physiological measures in their research, there is an awareness of serious gaps in the theoretical model and needs for refinement of methodologies and analytical strategies. Much more needs to be known about which biomarkers (and/or combinations of biomarkers) are most useful in predicting health outcomes in older age, and which psychosocial factors are the key predictors of change in these biomarkers over time. These researchers continue to wrest with measurement issues around “allostatic load” as they strive to keep apace of findings emerging from the biological literature on disease markers and key indicators of age-related physiological decline. The current workshop will focus on these pressing conceptual and measurement issues.
While the allostatic load model places emphasis on the biological pathways through which psychosocial factors have their effects on health outcomes, it should be emphasized that the fully integrative biopsychosocial model is recursive, with numerous and complex hypothesized bidirectional causal pathways. Real progress in integrative physiology requires the development of new analytical techniques that enable exploration of these multiple causative links, as well as advances in measurement at the level of the physical environment, the social context, the psychological subject, and the biological markers and mechanisms underlying health and disease.