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Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging

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Seeman, Teresa E., McEwen, Bruce S., Rowe, John W., Singer, Burton H.·2001·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.081072698PMC PMC31909

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Abstract

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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Background
Effectiveness of ultra-long-term lithium treatment: relevant factors and case series
Ferensztajn‐Rochowiak, E., Lewitzka, U., Chłopocka-Woźniak, M., & RYBAKOWSKI, J. K. (2024) · International Journal of Bipolar Disorders · doi:10.1186/s40345-024-00328-9 · Cited by 9
“Worth mentioning is also a paucity of chronic and uncompensated states of somatic co-morbidity in our patients, which is widely described in bipolar disorder, including cardiovascular, metabolic, neuroendocrine, and inflammatory diseases (Seeman et al. 2001).”
Background
Estradiol, via estrogen receptor β signaling, mediates stress-susceptibility in the male brain
Georgiou, P., Postle, A. F., Mou, T.-C. M., Potter, L. E., An, X., Zanos, P., Patton, M. S., Pultorak, K. J., Clark, S. M., Ngyuyen, V., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03027-8 · Cited by 8
Survey evidence of the decline in child abuse in younger Canadian cohorts
Ligier, F., Giguère, C., Séguin, M., & LESAGE, A. D. (2019) · European Journal of Pediatrics · doi:10.1007/s00431-019-03432-6 · Cited by 9
Respiratory Sinus Arrhythmia as a Physiological Resilience Marker for Children’s Health
Alen, N. V., Deer, L. K., & Hostinar, C. E. (2022) · Psychosomatic Medicine · doi:10.1097/psy.0000000000001057 · Cited by 9
“, allostatic load; (7)), as well as elevated systemic inflammation, which is associated with higher rates of health disorders (e.”
Background
Longitudinal associations between allostatic load, pet ownership, and socioeconomic position among U.S. adults aged 50+
Applebaum, J. W., McDonald, S. E., & Zsembik, B. A. (2023) · SSM - Population Health · doi:10.1016/j.ssmph.2023.101344 · Cited by 11
Association of education and receiving social transfers with allostatic load in the Swiss population-based CoLaus study
Nicod, E., Stringhini, S., Marques-Vidal, P. M., Paccaud, F. M., Waeber, G., Lamiraud, K., Vollenweider, P., & Bochud, M. (2014) · Preventive Medicine · doi:10.1016/j.ypmed.2014.03.013 · Cited by 9
“AL has also been associated with cardiovascular morbidity and mortality (Crimmins et al., 2003; Seeman et al., 2004; Seeman et al., 2001), as well as with poorer cognitive and physical functioning (Juster et al., 2010; Seeman et al., 1997).”
Further Validation of the Psychological Injury Risk Indicator Scale
Winwood, P. C., Peters, R., Peters, M., & Dollard, M. F. (2012) · Journal of Occupational and Environmental Medicine · doi:10.1097/jom.0b013e3182479f77 · Cited by 10
Stress, Alcohol Consumption, and the Hypothalamic-Pituitary-Adrenal Axis
Glavas, M. M., & Weinberg, J. (2006) · Humana Press eBooks · doi:10.1385/1-59259-952-4:165 · Cited by 9
Invited Commentary: Tapping the Tip of the Iceberg
Fischer, J. E., & Thayer, J. F. (2006) · American Journal of Epidemiology · doi:10.1093/aje/kwj120 · Cited by 9
“Higher scores on an allostatic load measure predicted higher mortality and poorer mental and physical functioning in retired Americans (16).”
Invited Commentary: Integrating Genomics and Social Epidemiology—Analysis of Late-Life Low Socioeconomic Status and the Conserved Transcriptional Response to Adversity
Belsky, D. W., & Snyder‐Mackler, N. (2017) · American Journal of Epidemiology · doi:10.1093/aje/kwx145 · Cited by 9
“As a multimarker measurement of a multidimensional, cumulative process of biological embedding, the CTRA is substantially aligned with allostatic load (34) and the emerging literature on so-called biological aging (35–37).”
Background
Analysis of socioeconomic disadvantage and pace of aging measured in saliva DNA methylation of children and adolescentsPreprint
Raffington, L., Belsky, D. W., Malanchini, M., Tucker–Drob, E. M., & Harden, K. P. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.04.134502 · Cited by 12
“In adults, the social determinants of health and aging have been studied using multi-organ system measures such as allostatic load (13) and, more recently, physiology-based measures of”
Background
Getting Under the Skin
Jackson, C. L., Dagher, R. K., Byun, J. S., Farhat, T., & Gardner, K. L. (2021) · Wiley eBooks · doi:10.1002/9781119374855.ch2 · Cited by 9
A novel approach for measuring allostatic load highlights differences in stress burdens due to race, sex and smoking status
Bailey, A., Payton, A., Fleming, J. F., Rager, J. E., & Jaspers, I. (2025) · PLoS ONE · doi:10.1371/journal.pone.0323788 · Cited by 8
“Additionally, given the inverse relationship with stress and atherosclerosis, HDL was assigned a weight of -0.25 [20,21].”
Influential
Allostatic load dynamics, Alzheimer's disease biomarkers, and progression in individuals with mild cognitive impairment: findings from the Alzheimer's Disease Neuroimaging Initiative
Souza‐Talarico, J. N., Perkhounkova, Y., Hein, M., Lee, J., Hefti, M. M., & Sindi, S. (2025) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.70140 · Cited by 9
“18 Previous studies showed higher ALI was associated with cognitive decline after 3years 12 and inversely associated with processing speed, general cognitive ability, knowledge, and performance.”
Breastfeeding Is Inversely Associated with Allostatic Load in Postpartum Women: Cross-Sectional Data from Nationally Representative US Women
Hsiao, B.-S., & Sibeko, L. N. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab302 · Cited by 13
Stress in bioarchaeology, epidemiology, and evolutionary medicine: an integrated conceptual model of shared history from the descriptive to the developmental
Temple, D. H., & Edes, A. N. (2022) · Oxford University Press eBooks · doi:10.1093/oso/9780198849711.003.0014 · Cited by 8
Biopsychosocial Correlates of Resting and Stress-Reactive Salivary GDF15: Preliminary Findings
Liu, C. C., Trumpff, C., Huang, Q., Juster, R., & Picard, M. A. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.106068 · Cited by 11
Personal mastery, multisystem physiological dysregulation and risk of functional decline in older adults: A prospective study in T aiwan
Wu, I., Hsiung, C. A., Chang, I., Wu, M., Chang, Y., & Hsu, C. (2014) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.12334 · Cited by 10
Resilience and Survival in Extreme Environments
Friedl, K. E., & Penetar, D. M. (2008) · CRC Press eBooks · doi:10.1201/9781420071788.ch7 · Cited by 9
Cumulative Physiologic Dysfunction and Pregnancy: Characterization and Association with Birth Outcomes
McKee, K. S., Seplaki, C. L., Fisher, S. G., Groth, S. W., & Fernandez, I. D. (2016) · Maternal and Child Health Journal · doi:10.1007/s10995-016-2103-0 · Cited by 11
“A limitation to our measure of CPD for pregnancy is that it did not contain any of the ‘‘primary neuroendocrine mediators’’ components, such as cortisol, used in the literature (McEwen 1998; Seeman et al. 2001).”
Social and spatial inequalities in allostatic load among adults in China: a multilevel longitudinal study
Mao, F., Astell‐Burt, T., Feng, X., Liu, Y., Dong, J., Liu, S., Wang, L., Jiang, Y., Dong, W., Zhou, M., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-031366 · Cited by 8
Can antipoverty programmes save lives? Quasi-experimental evidence from the Earned Income Tax Credit in the USA
Muennig, P. A., Vail, D. G., & Hakes, J. K. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-037051 · Cited by 9
Allostatic Stress and Inflammatory Biomarkers in Transgender and Gender Expansive Youth: Protocol for a Pilot Cohort Study
Cohen, M., Karrington, B., Trachtman, H., & Salas-Humara, C. (2021) · JMIR Research Protocols · doi:10.2196/24100 · Cited by 11
“Seeman et al [30] documented that among older adults, higher baseline AL was associated with increased 7-year mortality and decreased physical and cognitive function.”
Background
Punitive Social Policy and Vital Inequality
Nosrati, E., & KING, L. P. (2021) · International Journal of Health Services · doi:10.1177/00207314211024895 · Cited by 8
Preparedness, Planning, and Advances in Operational Response
Administration, N. O. A. A., Westerholm, D., Ainsworth, C. H., Barker, C. H., Brewer, P., Farrington, J. W., Justić, D., Kourafalou, V. H., Murawski, S. A., Shepherd, J. G., et al. (2021) · Oceanography · doi:10.5670/oceanog.2021.127 · Cited by 8
Allostatic load and risk of hearing impairment
Matthews, K., Dawes, P., Elliott, R., Maharani, A., Pendleton, N., & Tampubolon, G. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100496 · Cited by 9
What limits for acute care in the elderly?
Ricou, B., & Merlani, P. G. (2008) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0b013e3283007b91 · Cited by 8
Allostatic Load and Spinal Cord Injury: Review of Existing Research and Preliminary Data
Krause, J. S., DiPiro, N. D., Saunders, L. L., Newman, S. D., Banik, N. L., & Park, S. (2014) · Topics in Spinal Cord Injury Rehabilitation · doi:10.1310/sci2002-137 · Cited by 8
Psychometrics and Assessment of an Empathy Distance Gradient
Hollar, D. (2016) · Journal of Psychoeducational Assessment · doi:10.1177/0734282915623882 · Cited by 8
Issues and Solutions for Collecting Biological Specimen in Longitudinal Studies: Experience from the Community Child Health Network Research Network
O'Campo, P. J., BeLue, R., Borenstein, H., Vance, M. R., Lanzi, R. G., Schäfer, P., Jones, L., & Woolord, R. (2016) · Journal of Health Care for the Poor and Underserved · doi:10.1353/hpu.2016.0021 · Cited by 9
Views of a good life and allostatic load: Physiological correlates of theories of a good life depend on the socioeconomic context
Levine, C. S., Atkins, A. H., Waldfogel, H. B., & Chen, E. (2016) · Self and Identity · doi:10.1080/15298868.2016.1173090 · Cited by 8
“Additional work could also follow people over time in order to link their theories of a good life to cardiovascular disease or other clinical outcomes for which allostatic load indicates greater risk (Juster et al., 2010; McEwen & Seeman, 1999; Seeman et al., 2001).”
BackgroundMethodInfluential
Burnout of the Mind – Burnout of the Body?
Traunmüller, C., Gaisbachgrabner, K., Lackner, H. K., & Schwerdtfeger, A. R. (2016) · Journal of Psychophysiology · doi:10.1027/0269-8803/a000182 · Cited by 8
Social Factors Contributing to the Development of Allostatic Load in Older Adults: A Correlational- Predictive Study
Jinez, A. M., Cabriales, E. C. G., D’Alonzo, K. T., Esquivel, A. U., López-Rincón, F. J., & Salazar-González, B. C. (2018) · Aquichan · doi:10.5294/aqui.2018.18.3.5 · Cited by 7
“(33), a measure of allostatic load (AL) was designed to summarize levels of physiological activity across a range of regulatory systems, including: systolic blood pressure, diastolic blood pressure, body mass index, waist circunference, waist-hip ratio, total cholesterol, high-density lipoprotein (HDL), glycated hemog…”
Background
The “develOpment of metabolic and functional markers of Dementia IN Older people” (ODINO) Study: Rationale, Design and Methods
Picca, A., Ronconi, D., Coelho‐Júnior, H. J., Calvani, R., Marini, F., Biancolillo, A., Gervasoni, J., Primiano, A., Pais, C., Meloni, E., et al. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10020022 · Cited by 8
“These approaches are conceptualized within the notion of allostatic load, that is the exposure of cells and biological systems to recurrent or chronic stressors inflicting cumulative damage [12].”
Background
Collecting Biomarker Data in Longitudinal Surveys
Meena Kumari, B., & Benzeval, M. (2021) · Wiley series in probability and statistics · doi:10.1002/9781119376965.ch2 · Cited by 8

Authors: Seeman, T. E., McEwen, B. S., Rowe, J. W., & Singer, B. H.
Affiliations: Aetna (United States) (US)
ORCID: Seeman, Teresa E.
McEwen, Bruce S.
Rowe, John W.
Singer, Burton H.
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
DOI: 10.1073/pnas.081072698
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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Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging

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