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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There are reliable indices of early damage to regulatory systems, allostatic load, and cellular aging such as inflammation, telomere length, and epigenetic clock that can be measured during mid-life and serve as markers, risk factors, and likely mechanistic precursors to disease or early mortality.
“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
There is wealth of evidence establishing direct pathways between the SNS and physical health.
“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
The effects of allostatic load on outcomes result from contributions of multiple regulatory systems represented in the index.
“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]
The associations between baseline allostatic load and major outcomes were found over an initial 2.5-year follow-up and a longer 7-year follow-up.
“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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Biomarkers shared by frailty and sarcopenia in older adults: A systematic review and meta-analysis
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Giscombé, C. L., & Lobel, M. (2005) · Psychological Bulletin · doi:10.1037/0033-2909.131.5.662 · Cited by 370 · see citing works
Brody, G. H., Yu, T., Chen, E., Miller, G. E., Kogan, S. M., & Beach, S. R. H. (2013) · Psychological Science · doi:10.1177/0956797612471954 · Cited by 329 · see citing works
Social Network Characteristics and Cognition in Middle-Aged and Older Adults
Holtzman, R. E., Rebok, G. W., Saczynski, J. S., Kouzis, A. C., Doyle, K. W., & Eaton, W. W. (2004) · The Journals of Gerontology Series B · doi:10.1093/geronb/59.6.p278 · Cited by 318 · see citing works
The transition to parenthood as a critical window for adult health.
Saxbe, D., Rossin-Slater, M., & Goldenberg, D. (2018) · American Psychologist · doi:10.1037/amp0000376 · Cited by 315 · see citing works
Cumulative Disadvantage and Health: Long-Term Consequences of Obesity?
Ferraro, K. F., & Kelley‐Moore, J. A. (2003) · PubMed · Cited by 316 · see citing works
O’Rand, A. M., & Hamil‐Luker, J. (2005) · The Journals of Gerontology Series B · doi:10.1093/geronb/60.special_issue_2.s117 · Cited by 312 · see citing works
Gaab, J., Blättler, N., Menzi, T., Pabst, B., Stoyer, S., & Ehlert, U. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00069-0 · Cited by 309 · see citing works
“Since cortisol has been considered a primary mediator in the development of allostatic load (Seeman et al., 2001), further studies are needed to evaluate possible long-term effects of the neuroendocrine response differences we observed.”
Background“Shift-and-Persist” Strategies: Why Low Socioeconomic Status Isn’t Always Bad for Health
Chen, E., & Miller, G. E. (2012) · Perspectives on Psychological Science · doi:10.1177/1745691612436694 · Cited by 359 · see citing works
Seeman, T. E., Merkin, S. S., Crimmins, E. M., Koretz, B. K., Charette, S. L., & Karlamangla, A. S. (2007) · Social Science & Medicine · doi:10.1016/j.socscimed.2007.08.027 · Cited by 307 · see citing works
“Additional algorithms for scoring risk, including use of quartile cut-points (24, 32) and using reported medication use as a criterion for “high risk”, were also examined.”
MethodSelf-citationAge differences in allostatic load: an index of physiological dysregulation
Crimmins, E. M., Johnston, M., Hayward, M., & Seeman, T. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00099-8 · Cited by 303 · see citing works
“In other samples where this has been operationalized, those at risk have been defined as those in the highest risk quartile of the indicator for the MacArthur study (Seeman et al., 2001).”
BackgroundInfluentialSelf-citationThe Social Psychology of Health Disparities
Schnittker, J., & McLeod, J. (2005) · Annual Review of Sociology · doi:10.1146/annurev.soc.30.012703.110622 · Cited by 277 · see citing works
Capturing Social and Behavioral Domains and Measures in Electronic Health Records: Phase 2
Domains, B. (2015) · Cited by 299 · see citing works
Air Pollution, Stress, and Allostatic Load: Linking Systemic and Central Nervous System Impacts
Thomson, E. M. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190015 · Cited by 305 · see citing works
“For example, higher baseline allostatic load scores in men and women aged 70–79 were associated with a steeper decline in cognitive function over a seven year followup period [117].”
BackgroundHispanic paradox in biological risk profiles.
Crimmins, E., Kim, J. K., Alley, D., Karlamangla, A., & Seeman, T. (2007) · American Journal of Public Health · doi:10.2105/ajph.2006.091892 · Cited by 297 · see citing works
Self-citationKondo, M. C., Jacoby, S. F., & South, E. C. (2018) · Health & Place · doi:10.1016/j.healthplace.2018.03.001 · Cited by 301 · see citing works
“Among elderly populations, AL has been associated with cardiovascular disease, physical decline, cognitive function and depression (Juster et al., 2010; Seeman et al., 2001, 1997).”
BackgroundA systems approach to stress, stressors and resilience in humans
Oken, B., Chamine, I., & Wakeland, W. W. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.12.047 · Cited by 288 · see citing works
“For example, someone with PTSD is in a pathological lower utility attractor that could relate to the brain misperceiving the This decreased efficiency and ability of the human dynamical physiological system to stay in or get back to a functionally positive attractor basin is the negative effect of…”
Effect of Environmental Enrichment on Stress Related Systems in Rats
Moncek, F., Duncko, R., Johansson, B. B., & Jezova, D. (2004) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2004.01173.x · Cited by 282 · see citing works
Karlamangla, A. S., Singer, B. H., & Seeman, T. E. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000221270.93985.82 · Cited by 283 · see citing works
Self-citationPsoriasis: is the impairment to a patient’s life cumulative?
Kimball, A. B., Gieler, U., Linder, D., Sampogna, F., Warren, R. B., & Augustin, M. (2010) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2010.03705.x · Cited by 281 · see citing works
Quality of life in adolescent and young adult cancer patients: a systematic review of the literature
Quinn, G. P., Gonçalves, V., Sehovic, I., Bowman, M., & Reed, D. R. (2015) · Patient Related Outcome Measures · doi:10.2147/prom.s51658 · Cited by 276 · see citing works
“Measurement of allostatic load was guided by the work of Seeman et al 74 Overall, survivor and sibling groups both tended to have greater psychological distress than community norms. each group had a mean value that was close to the 80th percentile in community samples.”
Heppner, P. S., Crawford, E. F., Haji, U. A., Afari, N., Hauger, R. L., Dashevsky, B. A., Horn, P. S., Nunnink, S. E., & Baker, D. G. (2009) · BMC Medicine · doi:10.1186/1741-7015-7-1 · Cited by 274 · see citing works
“The selected factors that contribute to metabolic syndrome in this study closely approximate the secondary mediators of allostatic load, with the exception of serum triglycerides [46,47].”
Understanding social inequalities in health.
Marmot, M. G. (2003) · PubMed · doi:10.13016/knrh-6rzo · Cited by 273 · see citing works
Colen, C. G., Ramey, D. M., Cooksey, E. C., & Williams, D. R. (2017) · Social Science & Medicine · doi:10.1016/j.socscimed.2017.04.051 · Cited by 267 · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Seeman et al. 2001).”
BackgroundMitnitski, A. B., Song, X., & Rockwood, K. J. (2004) · The Journals of Gerontology Series A · doi:10.1093/gerona/59.6.m627 · Cited by 268 · see citing works
“As reviewed elsewhere (6,7), more precise estimates are being achieved through mathematical modeling of frailty and related constructs, such as allostatic load (8,9) and physiological complexity (10,11).”
BackgroundJuster, R.-P., Bizik, G., Picard, M., Arsenault-Lapierre, G., Sindi, S., Trepanier, L., Marin, M.-F., Wan, N., Sekerovic, Z., Lord, C., et al. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000289 · Cited by 268 · see citing works
“Although no studies to date have assessed AL regarding dementia, the cognitive declines found in the MacArthur cohort (Seeman et al., 2001; Seeman, MeEwen, et al., 1997) imply that it could be a useful tool for detecting biological signatures of certain forms of dementia over others.”
MethodSelf-citationAllostasis and allostatic load: expanding the discourse on stress and cardiovascular disease
Logan, J. G., & Barksdale, D. J. (2008) · Journal of Clinical Nursing · doi:10.1111/j.1365-2702.2008.02347.x · Cited by 268 · see citing works
“This finding suggests that higher allostatic load is associated with worse health outcomes (Seeman et al. 2001).”
Clinical characterization of allostatic overload
Fava, G. A., McEwen, B. S., Guidi, J., Gostoli, S., Offidani, E., & Sonino, N. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.05.028 · Cited by 265 · see citing works
“It has been expressed in a cumulative index encompassing a battery of biomarkers such as: resting systolic and diastolic blood pressure, body mass index, waist-hip ratio, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, glycosylated hemoglobin, fasting glucose, plasma C-reactive protein…”
BackgroundSelf-citationThe mortality rate as a function of accumulated deficits in a frailty index
Mitnitski, A. B., Mogilner, A. J., MacKnight, C., & Rockwood, K. J. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00082-9 · Cited by 264 · see citing works
“An alternative approach is to express mortality as a function of a small number of generalized variables that capture major physiological dimensions of the human organism (Rockwood et al., 1999, 2000; Mitnitski et al., 2001; Zuev et al., 2000; Seeman et al. 2001; Fried et al. 2001).”
BackgroundResultCumulative risk, maternal responsiveness, and allostatic load among young adolescents.
Evans, G. W., Kim, P., Ting, A. H., Tesher, H. B., & Shannis, D. (2007) · Developmental Psychology · doi:10.1037/0012-1649.43.2.341 · Cited by 355 · see citing works
“First, there is growing evidence that inefficient physiological mobilization and recovery rather than resting indices of physiological stress are particularly important precursors of morbidity (Gunnar & Vasquez, 2001; Haynes, 1991; Heim, Newport, Heit, & Graham, 2000; Linden et al., 1997; McEwen, 1998, 2002; Seeman et…”
BackgroundInfluentialThe theory of resilience and relational load
Afifi, T. D., Merrill, A. F., & Davis, S. M. (2016) · Personal Relationships · doi:10.1111/pere.12159 · Cited by 259 · see citing works
Surtees, P. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg272 · Cited by 252 · see citing works
Poverty and Biological Risk: The Earlier "Aging" of the Poor
Crimmins, E. M., Kim, J. K., & Seeman, T. E. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/gln010 · Cited by 246 · see citing works
Self-citationCombinations of biomarkers predictive of later life mortality
Gruenewald, T. L., Seeman, T. E., Ryff, C. D., Karlamangla, A. S., & Singer, B. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606215103 · Cited by 242 · see citing works
Self-citationAllostatic processes in the family
Repetti, R. L., Robles, T. F., & Reynolds, B. (2011) · Development and Psychopathology · doi:10.1017/s095457941100040x · Cited by 236 · see citing works
Broadening the FocusThe Need to Address the Social Determinants of Health
Braveman, P., Egerter, S. A., & Mockenhaupt, R. E. (2010) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2010.10.002 · Cited by 234 · see citing works
Cumulative Disadvantage and Health: Long-Term Consequences of Obesity?
Ferraro, K. F., & Kelley‐Moore, J. A. (2003) · American Sociological Review · doi:10.2307/1519759 · Cited by 337 · see citing works
Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors
Guida, J. L., Ahles, T. A., Belsky, D., Campisi, J., Cohen, H. J., DeGregori, J., Fuldner, R., Ferrucci, L., Gallicchio, L., Gavrilov, L., et al. (2019) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djz136 · Cited by 216 · see citing works
Cohen, A. A., Milot, E., Yong, J., Seplaki, C. L., Fülöp, T., Bandeen‐Roche, K., & Fried, L. P. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.01.004 · Cited by 224 · see citing works
“Concordant with studies on allostatic load and aging (Crimmins et al., 2003; Glei et al., 2007; Gruenewald et al., 2009; Karlamangla et al., 2002; Seeman et al., 2001; Seplaki et al., 2006; Szanton et al., 2009), several lines of evidence in this study support the hypothesis of dysregulation in…”
Social Isolation and Adult Mortality: The Role of Chronic Inflammation and Sex Differences
Yang, Y. C., McClintock, M. K., Kozloski, M., & Li, T. (2013) · Journal of Health and Social Behavior · doi:10.1177/0022146513485244 · Cited by 222 · see citing works
“Laboratory research has long documented that stress has direct physiological effects on multiple regulatory systems through activation of the hypothalamic-pituitary-adrenal (HPA)axis and sympathetic nervous system (SNS), which modulate immune function and inflammatory processes (Seeman et al. 2001; Selye 1956).”
BackgroundNeural bases of moderation of cortisol stress responses by psychosocial resources.
Taylor, S. E., Burklund, L. J., Eisenberger, N. I., Lehman, B. J., Hilmert, C. J., & Lieberman, M. D. (2008) · Journal of Personality and Social Psychology · doi:10.1037/0022-3514.95.1.197 · Cited by 219 · see citing works
“Although the release of cortisol in response to real stressors is adaptive and essential for survival, heightened or prolonged activation of the HPA axis has been shown to have deleterious physical and psychological effects (McEwen, 1998; T. E. Seeman, McEwen, Rowe, & Singer, 2001 ).”
Barboza‐Solís, C., Kelly‐Irving, M., Fantin, R., Darnaudéry, M., Torrisani, J., Lang, T., & Delpierre, C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417325112 · Cited by 216 · see citing works
“Psychiatry Psychiatr Epidemiol 39(9):695–702.”
Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review
Burback, L., Brémault‐Phillips, S., Nijdam, M. J., McFARLANE, A. C., & Vermetten, E. H. G. J. M. (2023) · Current Neuropharmacology · doi:10.2174/1570159x21666230428091433 · Cited by 232 · see citing works
Of sound mind and body: depression, disease, and accelerated aging
Wolkowitz, O. M., Reus, V. I., & Mellon, S. H. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.1/owolkowitz · Cited by 213 · see citing works
“The “cost” to the organism of maintaining these physiological responses over prolonged periods has been termed “allostatic load”(13) or “arousal pathology,”(14) and it has repeatedly been associated with poor medical outcomes.(12) In addition to chronicity of the stress response, certain psychological, environmental,…”
Allostatic Load and Frailty in Older Adults
Gruenewald, T. L., Seeman, T. E., Karlamangla, A. S., & Sarkisian, C. A. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02389.x · Cited by 207 · see citing works
“In the MSSA cohort, greater levels of AL have been shown to predict greater risk of cognitive and physical disability and allcause mortality over time.(21,22) Frailty is also linked to disability and mortality in the MSSA cohort; a recent analysis indicated that older adults who developed frailty at 3-year follow-up h…”
Self-citation
- 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 › Neuropsychology and Physiological 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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