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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
In the citing paper
“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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BackgroundAssociation of allostatic load with overall survival in epithelial ovarian cancer
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BackgroundFemale fecundability is associated with pre‐pregnancy allostatic load: Analysis of a Chinese cohort
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“Note that while differences were found when using neuroendocrine (stress hormones and DHEA-S) versus metabolic syndrome biomarkers (glycolipids, blood pressure, adiposity), the multisystemic AL index was better than using only single biomarkers or systemic clusters to predict outcomes.(72) In a similar cross-sectional…”
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BackgroundApplication of Allostatic Load Theory in Cancer Management and Treatment Outcomes
Alamoudi, F. A., George, T. J., Horgas, A. L., Huo, Z., & Yoon, S. L. (2023) · JCO Oncology Practice · doi:10.1200/op.22.00530 · Cited by 7
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“Finally, the AL index was the sum of scores in each category (Misiak et al., 2018; Seeman et al., 2001).”
MethodCumulative Risk and Physiological Stress Responses in African American Adolescents
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“…in amniotic fl uid [34], have been shown to have limited clinical value in predicting PTB [32 – 34 Prenatal AL has been calculated by creating a composite score of primary (e.g., cortisol) and secondary (systolic and diastolic blood pressure) mediators, henceforth referred to as biomarkers [37, 38].”
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“This biological phenomenon manifests as dysregulation of multiple physiological systems, including the immune and sympathetic nervous systems, cardiovascular and metabolic processes and the hypothalamic-pituitary-adrenal axis (Seeman et al., 2001).”
Xu, S., Zhang, G., Xu, Y. L., Yu, C., Wu, R., Li, Z. H., Li, T., Cui, X., Huang, X., Zhou, S., et al. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1724572 · Cited by 5
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“The mathematical difference between the anabolic and catabolic indices, which was also computed, creates an index which is fairly similar to the one used by Seeman, McEwen, Rowe, and Singer (2001) to measure allostatic load, although with the opposite sign.”
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InfluentialAkagi, K., Koizumi, K., Kadowaki, M., Kitajima, I., & Saito, S. (2023) · Cells · doi:10.3390/cells12182297 · Cited by 5
“…glycosylated hemoglobin, blood glucose, insulin, albumin, creatinine, and homocysteine), cardiovascular/respiratory function (systolic blood pressure, diastolic blood pressure, peak expiratory flow, and heart rate), and anthropometric measurements (waist-to-hip ratio and body mass index) [136,137].”
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“41,42 Over the last 20 years, this concept has been developed to create frailty indices in an attempt to quantify physical deficits in patients and use that to predict postoperative outcomes.”
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“This dysregulation of physiological systems that occurs with prolonged or poorly regulated stress responses has been called “allostatic load” (Seeman et al. 2001) and is usually viewed as a maladaptive consequence of novel stressors of prolonged duration.”
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“In addition, we measured AL (9), as well as exposure to childhood trauma and subjective chronic stress.”
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Bello, G., Teitelbaum, S. L., Lucchini, R. G., Dasaro, C. R., Shapiro, M. Z., Kaplan, J. R., Crane, M. A., Harrison, D. J., Luft, B. J., Moline, J. M., et al. (2017) · American Journal of Industrial Medicine · doi:10.1002/ajim.22786 · Cited by 5
“For example, allostatic load, a cumulative risk index of multisystem dysregulation, is commonly computed by counting the number of stress, inflammatory, and metabolic biomarkers for which an individual falls outside the clinically “healthy” range.(21,23,43) Biomarkers typically used for allostatic load include stress…”
BackgroundPatterns of health inequalities
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“influence physical and mental health via allostatic load [22] while also producing synergies with the”
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Health and ill health in working women – balancing work and recovery
Schwarz, U. V. T. (2008) · KTH Publication Database DiVA (KTH Royal Institute of Technology) · Cited by 5
The Nature of Women's Career Development: Determinants and Consequences of Career Patterns
Huang, Q. (2006) · PsycEXTRA Dataset · doi:10.1037/e530032013-001 · Cited by 5
Perceived Stress and Physiological DysregulationPreprint
Goldman, N., Glei, D. A., Seplaki, C. L., Liu, I.-W., & Weinstein, M. (2004) · RePEc: Research Papers in Economics · Cited by 5
Chapman, T. M., McAlister, K. L., Moore, K., Wang, W., & Belcher, B. R. (2025) · Annals of Behavioral Medicine · doi:10.1093/abm/kaaf031 · Cited by 3
“24,26,27 Since AL is a cumulative measure of stress-induced physiological dysregulation, 11,22,87 its increase over time may result in the early onset of chronic diseases.”
Finlay, S., Adegboye, O. A., Rudd, D., McDERMOTT, B. M., & Sarnyai, Z. (2025) · Psychological Medicine · doi:10.1017/s0033291725102377 · Cited by 5
“…between elevated AL index and already existing physical and mental health conditions, longitudinal studies have shown that elevated AL also predicts later development of impaired functioning, morbidity, and mortality (Guidi et al., 2020; Seeman, McEwen, Rowe, & Singer, 2001; See-man et al., 1997).”
Muldoon, O. T., O’Donnell, A. T., Foran, A., Whelan, E., Skilton, L., Lebedová, A., Lashkay, A., Griffin, S. M., Gallagher, S., McMahon, G., et al. (2026) · European Review of Social Psychology · doi:10.1080/10463283.2026.2631340 · Cited by 4
Afifi, T. D., Callejas, M. L. A., & Harrison, K. (2020) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780190679446.013.11 · Cited by 4
Bruun-Rasmussen, N. E., Napolitano, G. M., Bojesen, S. E., Ellervik, C., Rasmussen, K., & Lynge, E. (2024) · International Journal of Public Health · doi:10.3389/ijph.2024.1606585 · Cited by 4
“AL was de fi ned consistently with previous studies and in accordance with the initial de fi nition of AL by Seeman et al., 1997 [27, 33]; ten biomarkers were available for the present study representing the; in fl ammatory system (C-reactive protein (CRP), albumin); metabolic system (high-density…”
Martocchia, A., Stefanelli, M., Gallucci, M., Noale, M., Maggi, S., Cassol, M., Postacchini, D., Proietti, A., Barbagallo, M., Dominguez, L. J., et al. (2024) · Aging Clinical and Experimental Research · doi:10.1007/s40520-024-02849-w · Cited by 4
The Longitudinal Relationship Between Allostatic Load and Multimorbidity Among Older Americans
Mira, R. S., Newton, T., & Sabbah, W. (2025) · Geriatrics · doi:10.3390/geriatrics10040084 · Cited by 4
“Secondary mediators include biomarkers such as cholesterol, glycosylated haemoglobin, resting systolic and diastolic blood pressure, c-reactive protein, and waist/hip ratio [23,25].”
InfluentialLudwig-Borycz, E. F., Lee, H., Ryan, L. H., Heeringa, S. G., McEvoy, C. T., Wolfson, J. A., Agrawal, A., Langa, K. M., & Leung, C. W. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70480 · Cited by 3
Childhood allostatic load predicts cardiometabolic health in adulthood
Hinz, E., Vitali, A. J., Tong, G., Pontzer, H., & Copeland, W. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2508549122 · Cited by 4
Diet Quality and Biological Risk in a National Sample of Older Americans
Choi, Y. J., Ailshire, J., Kim, J. K., & Crimmins, E. M. (2021) · Journal of Aging and Health · doi:10.1177/08982643211046818 · Cited by 4
“…of biological systems representing cardiometabolic functioning, kidney functioning, and inflammation, which indicates increased risk of diseases, impairment, and mortality or accelerated aging (Beckie, 2012; Crimmins et al., 2008; Guidi et al., 2021; Juster et al., 2010; Seeman et al., 2001, 2004).”
BackgroundHao, B., Chen, J., Cai, Y., Li, H., Zhu, Z., Xu, W., & Liu, H. (2023) · BMC Geriatrics · doi:10.1186/s12877-023-04091-x · Cited by 4
“Most previous studies on AL have used public data from large-sample health surveys [10, 11, 16, 34].”
BackgroundDattagupta, J., Banerjee, A., Maji, B. K., & Chattopadhyay, P. K. (2024) · International Journal of Adolescent Medicine and Health · doi:10.1515/ijamh-2024-0052 · Cited by 4
Barbosa, B. J. A. P., Souza‐Talarico, J. N., de Jesus, M. C. F., Mota, G. P. S., de Oliveira, M. O., Cassimiro, L., Avolio, I. B., Trés, E. S., Borges, C. R., Teixeira, T. B. M., et al. (2024) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2024.108365 · Cited by 4
Mei, Y., Li, A., Zhao, J., Li, Y., Zhou, Q., Yang, M., Zhao, M., Xu, J., Li, K., Yin, G., et al. (2024) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2024.175498 · Cited by 4
Castellano, G., Silva, J. B. D., & Pietropaolo, S. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110179 · Cited by 5
Long-term Economic Distress and Growing Educational Inequity in Life Expectancy
Geronimus, A. T., Waidmann, T., Bound, J., Pancini, V., & Yang, M. (2025) · Epidemiology · doi:10.1097/ede.0000000000001843 · Cited by 4
Villanea, M. S. (2012) · Americanae (AECID Library) · Cited by 4
DOES LOWER SUBJECTIVE SOCIAL STATUS YIELD RISKIER BIOMARKER PROFILES?
Gersten, O., Timiras, P. S., & Boyce, W. T. (2014) · Journal of Biosocial Science · doi:10.1017/s002193201400042x · Cited by 4
“Investigations of the neuroendocrine system are important because recent large-scale studies, including neuroendocrine markers for the first time, have linked dysregulated neuroendocrine biomarker profiles to increased risk of a number of health problems, including greater physical and cognitive declines and mortality…”
BackgroundRelation Between Aggression Exposure During Youth and Later Resting Skin Conductance Levels
Barry, S., Emhoff, S. M., Rabkin, A. N., Olezeski, C. L., Lehrbach, M., Szczypinski, B. J., & Gordis, E. B. (2016) · Journal of Aggression Maltreatment & Trauma · doi:10.1080/10926771.2016.1257527 · Cited by 4
Kibe, M., Mizuno, Y., Masuoka, H., Kosaka, S., Natsuhara, K., Hirayama, K., Inthavong, N., Kounnavong, S., Tomita, S., & Umezaki, M. (2023) · American Journal of Human Biology · doi:10.1002/ajhb.23976 · Cited by 5
“Various physiological indicators have been used to evaluate allostatic load (Beckie, 2012; Schulkin, 2004; Seeman et al., 2001).”
MethodAllostatic load in children: The cost of empathic concern
Phua, D. Y., Chen, H., Yap, F. K. P., Chong, Y. S., Gluckman, P. D., Broekman, B. F. P., Eriksson, J. G., & Meaney, M. J. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2217769120 · Cited by 6
“Cumulative measures of these stress mediators provide an index of allostatic load that is consistently associated with various health risks (19), such as obesity (20), adverse pregnancy outcomes (21), cardiovascular diseases (22), and even premature mortality (23).”
Interpersonal touch and the importance of romantic partners for older adults’ neuroendocrine health
Navyte, G., Gillmeister, H., & Meena Kumari, B. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106414 · Cited by 5
“Over time, repeated exposure to stressful experiences can increase the body ’ s allostatic load (AL), which represents the cumulative physiological burden resulting from the need for continuous adjustment to maintain allostasis (Seeman et al., 2001).”
BackgroundInfluential
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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