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Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging
Open accessAbstract
Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70–79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.
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“Fortunately, although diagnosable disease does not occur until later in life, there are several reliable indices of early damage to regulatory systems, allostatic load (Hwang et al., 2014; Robertson et al., 2017; Seeman et al., 2001), and cellular aging such as inflammation, telomere length, and epigenetic clock (Chen et al., 2016; Codd et al., 2013; Emerging Risk Factors Collaboration et al., 201”
From More than a feeling: A unified view of stress measurement for population science (2018) · cites this paper as Seeman et al., 2001
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“There is also wealth of evidence establishing direct pathways between the SNS and physical health (Danese and McEwen, 2012; McLaughlin et al., 2014a; Seeman et al., 2001).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Seeman et al., 2001
In the citing paper
“the effects were found to result from the contributions of multiple regulatory systems represented in the index, 164”
From Socio‐economic differentials in peripheral biology: Cumulative allostatic load (2010) · cites this paper as [164]
In the citing paper
“These associations were found both with respect to an initial 2.5 year follow-up period 176 as well as a longer 7-year period, 164”
From Socio‐economic differentials in peripheral biology: Cumulative allostatic load (2010) · cites this paper as [164]
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“The use of a cumulative index allowed us to better capture the sum total of the more modest differences in some of the biomarkers that contribute to significant differences in overall biological risks by NSES.37 In addition, our findings indicate consistent effects across race/ethnicity, gender and IPR subgroups, sugg…”
BackgroundInfluentialSelf-citationAllostatic load is associated with chronic conditions in the Boston Puerto Rican Health Study
Mattei, J., Demissie, S., Falcon, L. M., Ordovas, J. M., & Tucker, K. (2010) · Social Science & Medicine · doi:10.1016/j.socscimed.2010.02.024 · Cited by 203
“Reports from the MacArthur Studies show that AL predicted morbidity and mortality similarly to MetS, and they attributed the largest contribution to the secondary mediators (Karlamangla et al., 2002; Seeman et al., 2001).”
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“As already suggested by the original authors, we expanded the classical score to account additionally for immunological, blood coagulation, and metabolic processes because the AL index has been theoretically conceptualized as a comprehensive marker of cumulative dysregulation across stress-sensitive physiological syst…”
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“First, we compared the current cutoff points with those published in previous studies of older adults aged 40+ (26) and 65+ years (37) from the same NHANES data and older adults aged 70–79 years from a different data set (17).”
BackgroundResultAllostatic Load: A Mechanism of Socioeconomic Health Disparities?
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BackgroundCardiovascular Disease and Homelessness
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“…demonstrated that the allostatic load index, consisting of 10 biological parameters including estimates of HPA axis activity, is positively associated with the risk for 7-year mortality as well as declines in cognitive and physical functioning (Seeman et al., 2001; Karlamangla et al., 2002).”
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“This is a potentially sensitive measure (Seeman et al. 2001) of physical weathering that may detect differences among younger age groups before morbidity onset.”
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“, blood pressure, cortisol, catecholamines, glycated hemoglobin, waist circumference, cholesterol, inflammatory markers), and allocating individuals scores based on the number of variables on which values are elevated compared with the sample distribution (9, 10).”
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“…with females in one treatment being in poorer condition based on expectations from the literature, we used the multivariate test developed by Seeman et al. (2001, 2004) to assess what they termed ‘‘physiological dysregulation’’ (or ‘‘allostatic load’’, Seeman et al. 2001), calculated as the…”
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BackgroundEvidence of accelerated aging among African Americans and its implications for mortality
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“Given that cumulative risk or allostatic load measures rely on counts of biomarkers for which a subject falls into a “high risk” category (Seeman et al., 2001) they may lose some of the information that could be gained from continuousmeasures (Levine and Crimmins, 2014).”
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“This finding is in line with previous work showing covariation between aspects of psychological wellbeing and long-term patterns of physiological activation [48] and, given the well-established link between allostatic load and mortality [11], it offers a strong biological foundation for the growing body of research sh…”
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Social allostasis: anticipatory regulation of the internal milieu
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“, brain morphology and decreases in memory function (Sapolsky, 1992, 1995), and increases allostatic load (McEwen and Stellar, 1993; Johnston-Brooks et al., 1998; McEwen, 1998; Seeman et al., 2001).”
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“One can make an analogy with the allostatic load concept from McEwen ( 1998 ), Seeman, McEwen, Rowe, and Singer ( 2001 ), and Sun, Wang, Zhang, and Li ( 2007 ).”
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BackgroundInfluentialDo Chronic Stressors Lead to Physiological Dysregulation? Testing the Theory of Allostatic Load
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“007 and all-cause mortality in cross-sectional and follow-up studies [57,56,58,135,134,133].”
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“Indirect evidence for this originates from studies that found that cumulative physiologic wear and tear or allostatic load increases the risk of cognitive decline.(52,53) It is also possible that HPA axis dysregulation resulted from repeated depressive episodes earlier in life,(54) which, in turn, led to brain volume…”
BackgroundStress‐related Development of Obesity and Cortisol in Women
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“Failing to habituate – or the loss of allostasis, might lead to a higher susceptibility to disease or declines in physical and cognitive functioning (Seeman et al., 2001; Karlamangla et al., 2002).”
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“Intraabdominal fat distribution is commonly cited as a physiological marker of chronic psychological stress, particularly the influence of a chronic activation of the hypothalamic-pituitary-adrenal axis (100).”
BackgroundCarroll, J., Seeman, T. E., Olmstead, R. E., Melendez, G., Sadakane, R., Bootzin, R. R., Nicassio, P. M., & Irwin, M. R. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.02.010 · Cited by 140
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“To date, most studies of gene- environment interplay are cross- sectional or use longitudinal data without explicit modeling of life course features, including pathways, transitions, trajectories, durations, or timing (Conley 2016; Shanahan and Boardman 2009).”
BackgroundClinical assessment of allostatic load and clinimetric criteria
Fava, G. A., Guidi, J., Semprini, F., Tomba, E., & Sonino, N. (2010) · Psychotherapy and Psychosomatics · doi:10.1159/000318294 · Cited by 131
Early Life Adversity and Adult Biological Risk Profiles
Friedman, E. M., Karlamangla, A. S., Gruenewald, T. L., Koretz, B. K., & Seeman, T. E. (2015) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000147 · Cited by 134
“In sum, we expand upon previous work by examining the impact of ELA on cumulative adult biological risk profiles—a known predictor of increased risks for major adult health outcomes such as cognitive and physical impairment, CVD, and mortality (51).”
MethodSelf-citationNater, U. M., Hoppmann, C. A., & Scott, S. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.09.008 · Cited by 135
“While we did not assess stress over lifetime, our observation of age-related increases in endocrine and autonomic functioning could reflect age-related accumulation of stress (Seeman et al., 2001).”
BackgroundBrody, G. H., Yu, T., Chen, Y., Kogan, S. M., Evans, G. W., Beach, S. R. H., Windle, M. T., Simons, R. L., Gerrard, M., Gibbons, F. X., et al. (2012) · Developmental Psychology · doi:10.1037/a0028847 · Cited by 142
“This inability to turn off the demand response sets in motion a cascade of physiological changes that contribute to the development of chronic illnesses, including hypertension, cardiac disease, diabetes, stroke, and psychiatric disorders (Seeman et al., 2001).”
Social relationships and allostatic load in Taiwanese elderly and near elderly
Seeman, T. E., Glei, D. A., Goldman, N., Weinstein, M., Singer, B., & Lin, Y. (2004) · Social Science & Medicine · doi:10.1016/j.socscimed.2004.03.027 · Cited by 133
Self-citationCastagné, R., Garès, V., Karimi, M., Chadeau‐Hyam, M., Vineis, P., Delpierre, C., & Kelly‐Irving, M. (2018) · European Journal of Epidemiology · doi:10.1007/s10654-018-0364-1 · Cited by 133
“used data from the MacArthur Successful Aging Study, a longitudinal study of men and women aged 70-79 living in the United States and reported that higher baseline AL scores were associated with significantly greater risk for mortality within 7 years [28].”
InfluentialSeeman, T. E., Gruenewald, T. L., Karlamangla, A. S., Sidney, S., Liu, K., McEwen, B. S., & Schwartz, J. E. (2009) · American Journal of Human Biology · doi:10.1002/ajhb.21018 · Cited by 136
“Earlier research, however, has operationalized AL in terms of various summative indices (Karlamangla, 2002; Seeman et al., 2001).”
Self-citationLifestyle and Successful Aging: An Overview
Franklin, N. C., & Tate, C. A. (2008) · American Journal of Lifestyle Medicine · doi:10.1177/1559827608326125 · Cited by 137
“Since 1988, researchers in the MacArthur Study of Successful Aging have explored indicators and predictors of physical and cognitive functioning in robust older adults to interpret successful aging.(13,55) Rowe and Kahn(43) developed the leading biomedical model for successful aging based on the MacArthur longitudinal…”
BackgroundPasquali, R. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06569.x · Cited by 135
Purposeful Engagement, Healthy Aging, and the Brain
Ryff, C. D., Heller, A. S., Schaefer, S. M., van Reekum, C. M., & Davidson, R. J. (2016) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-016-0096-z · Cited by 141
Allostatic load and biological anthropology
Edes, A. N., & Crews, D. E. (2017) · American Journal of Physical Anthropology · doi:10.1002/ajpa.23146 · Cited by 130
Capturing Social and Behavioral Domains in Electronic Health Records: Phase 1
Domains, B. (2014) · Cited by 128
The Longitudinal Aging Study Amsterdam: cohort update 2019 and additional data collections
Hoogendijk, E. O., Deeg, D. J. H., de Breij, S., Klokgieters, S. S., Kok, A. A. L., Stringa, N., Timmermans, E. J., van Schoor, N. M., van Zutphen, E. M., van der Horst, M. H. L., et al. (2019) · European Journal of Epidemiology · doi:10.1007/s10654-019-00541-2 · Cited by 131
Gustafsson, P. E., Sebastiån, M. S., Janlert, U., Theorell, T., Westerlund, H., & Hammarström, A. (2014) · American Journal of Public Health · doi:10.2105/ajph.2013.301707 · Cited by 139
Social status and biological dysregulation: The “status syndrome” and allostatic load
Seeman, M. S., Merkin, S. S., Karlamangla, A. S., Koretz, B. K., & Seeman, T. E. (2014) · Social Science & Medicine · doi:10.1016/j.socscimed.2014.08.002 · Cited by 137
“As noted, prior work has shown that measures of allostatic load are robust in predicting health-related outcomes (Juster et al., 2010; Seeman et al., 2001).”
InfluentialSelf-citationCumulative Disadvantage and Health: Long-Term Consequences of Obesity?
Ferraro, K. F., & Kelley‐Moore, J. A. (2003) · American Sociological Review · doi:10.1177/000312240306800503 · Cited by 125
Religious Service Attendance and Allostatic Load Among High-Functioning Elderly
Maselko, J., Kubzansky, L., Kawachi, I., Seeman, T., & Berkman, L. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e31806c7c57 · Cited by 124
“Furthermore, studies using different forms of the AL score itself have found them to perform equivalently (20,21,36,37).”
BackgroundMethodSelf-citationPerceived Weight Discrimination and 10-Year Risk of Allostatic Load Among US Adults
Vadiveloo, M., & Mattei, J. (2017) · Annals of Behavioral Medicine · doi:10.1007/s12160-016-9831-7 · Cited by 124
“Given that high allostatic load has been shown to be robustly associated with type 2 diabetes, hypertension, cardiovascular disease, and mortality [39, 49], targeted efforts to reduce weight discrimination are warranted.”
BackgroundMetabolic syndrome in women with chronic pain
Loevinger, B. L., Muller, D., Alonso, C. M., & Coe, C. L. (2006) · Metabolism · doi:10.1016/j.metabol.2006.09.001 · Cited by 124
“The top quartile for A1c and other biological parameters has been used to define those at greater health risk [40] and, consistent with the intent of the ATP III definition, the Women’s Health Study data showed that an A1c level greater than 5.”
MethodThe Emerging Theoretical Framework of Life Course Health Development
Halfon, N., & Forrest, C. B. (2017) · Springer eBooks · doi:10.1007/978-3-319-47143-3_2 · Cited by 132
Social hallmarks of aging: Suggestions for geroscience research
Crimmins, E. M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101136 · Cited by 126
““Allostatic load” was one of the early formulations for including multisystem biology changes into the study of aging (Kim et al., 2018; Seeman et al., 2001).”
BackgroundEnvironmental stress, psychological stress and allostatic load
Clark, M. S. G., Bond, M. J., & Hecker, J. R. (2006) · Psychology Health & Medicine · doi:10.1080/13548500500429338 · Cited by 122
“In this study and in a subsequent 7-year follow-up (Seeman, McEwen, Rowe, & Singer, 2001 ) they found that higher allostatic load scores were associated with poorer physical and cognitive functioning, greater risk of cardiovascular disease and increased mortality.”
BackgroundStress, Inflammation, and Aging
Lavretsky, H., & NEWHOUSE, P. A. (2012) · American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31826573cf · Cited by 133
Webb, L. E., Veenhoven, R., Harfeld, J. L., & Jensen, M. B. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13983 · Cited by 124
PURPOSE IN LIFE PROTECTS AGAINST COGNITIVE DECLINE AMONG OLDER ADULTS
Byrd, D., Gamaldo, A. A., Allaire, J. C., & Whitfield, K. E. (2019) · The American journal of geriatric psychiatry · doi:10.1016/j.jagp.2019.01.010 · Cited by 100
Riosmena, F., Everett, B. G., Rogers, R. G., & Dennis, J. A. (2014) · International Migration Review · doi:10.1111/imre.12102 · Cited by 121
Daly, M., Sutin, A. R., & Robinson, E. (2019) · Psychological Science · doi:10.1177/0956797619849440 · Cited by 121
“In line with prior research (e.g., Daly et al., 2017; Hampson et al., 2009), we drew on biomarkers of cardiovascular, immune, and metabolic system functioning to generate a composite index of physiological dysregulation indicative of allostatic load (Seeman et al., 2001).”
BackgroundResultInfluentialUpchurch, D. M., Stein, J., Greendale, G. A., Chyu, L., Tseng, C.-H., Huang, M.-H., Lewis, T. T., Kravitz, H. M., & Seeman, T. (2015) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000175 · Cited by 101
“Although alternative methods for summarizing biomarker scores have been investigated, comparable results have been found regardless of method (12,17,45,46).”
ResultSelf-citationDimensions of religious involvement and leukocyte telomere length
Hill, T. D., Ellison, C. G., Burdette, A. M., Taylor, J., & Friedman, K. L. (2016) · Social Science & Medicine · doi:10.1016/j.socscimed.2016.04.032 · Cited by 116
“Following previous research (e.g., Crimmins et al., 2003; Geronimus et al., 2006; Seeman et al., 2001), we dichotomized each biomarker according to a high-risk cutoff criterion.”
MethodStümvoll, M., Tataranni, P. A., Stefan, N., de Courten, B. V., & Bogardus, C. (2003) · Diabetes · doi:10.2337/diabetes.52.4.903 · Cited by 116
Promoting physical activity among older adultsFrom ecology to the individual
Satariano, W. A. (2003) · American Journal of Preventive Medicine · doi:10.1016/s0749-3797(03)00183-1 · Cited by 119
Senn, T. E., Walsh, J. L., & Carey, M. P. (2014) · Annals of Behavioral Medicine · doi:10.1007/s12160-014-9591-1 · Cited by 122
Successful ageing: from cell to self
LUPIEN, S. J., & Wan, N. (2004) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2004.1516 · Cited by 128
“A substantial body of research shows that social support is a key determinant of successful ageing (Rowe & Kahn 1998; Leviatan 1999; Unger et al. 1999; Seeman et al. 2001b).”
Background
Metadata
- Authors
- Seeman, T. E., McEwen, B. S., Rowe, J. W., & Singer, B. H.
- Affiliations
- Aetna (United States) (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-04-03
- Volume
- 98
- Issue
- 8
- Pages
- 4770-4775
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC31909
- OpenAlex
- W2015252215
- Cited by
- 1,385
- References
- 24
- Citations by year
- 2026: 68 · 2025: 68 · 2024: 52 · 2023: 51 · 2022: 73 · 2021: 86 · 2020: 86 · 2019: 91 · 2018: 66 · 2017: 67 · 2016: 79 · 2015: 63 · 2014: 79 · 2013: 49 · 2012: 50
- FWCI
- 30.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag017056-03)
- National Institute on Aging (AG00586, AG 17056)
- Topics
- Social Sciences › Health › Health disparities and outcomes
- Social Sciences › Psychology › Developmental and Educational Psychology › Aging and Gerontology Research
- Health Sciences › Health Professions › General Health Professions › Health, psychology, and well-being
- Keywords
- allostatic load, successful aging, older adults, mortality, cognitive decline, cardiovascular disease, metabolic syndrome, biological mediators, aging
- MeSH terms
- Aged, Aging, Female, Humans, Male, Regression Analysis, Stress, Physiological, Microvascular Angina
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