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Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging
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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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Allostatic load scoring using item response theory
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“They are related to the notion of allostatic load [50], the decline in adaptive capacity (homeostenosis) [51–54], the decline in resistance to stresses [5,55–57], aging-related physiological norms, and heterogeneity in longitudinal data.”
BackgroundChildhood cumulative risk and later allostatic load: Mediating role of substance use.
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“Allostatic load (AL) is evaluated by a composite measure that is empirically-supported, and is associated with and predictive of functional decline, disease, and death (Juster et al., 2010; Karlamangla et al., 2006; Reuben et al., 2002; Seeman et al., 2001).”
Mattei, J., Bhupathiraju, S. N., & Tucker, K. L. (2013) · Journal of Nutrition · doi:10.3945/jn.113.180141 · Cited by 51
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“Allostatic load has been associated with increased risk of incident CVD and mortality, and declines in cognitive and physical function, and these results have been shown to be stronger than those observed for metabolic syndrome (6).”
Allostatic Load is Associated with Symptoms in Chronic Fatigue Syndrome Patients
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“High baseline levels of AL have been associated with cardiovascular disease (CVD), mortality and decline in physical and cognitive functioning in a prospective study of 70–79 year old persons over a 7-year period [3,4].”
BackgroundResultAllostatic Load and Clinical Risk as Related to Sense of Coherence in Middle-Aged Women
Lindfors, P., Lundberg, O., & Lundberg, U. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000232267.56605.22 · Cited by 49
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BackgroundResultPsychological Stress: A Predisposing and Exacerbating Factor in Periodontitis
Spector, A. M., Postolache, T. T., Akram, F., Scott, A. J., Wadhawan, A., & Reynolds, M. A. (2020) · Current Oral Health Reports · doi:10.1007/s40496-020-00282-2 · Cited by 47
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“The broad spectrum of available markers enabled us to form an adequate and comprehensive AL profile (7), which is probably a more valid indication of current health status than metabolic syndrome or independent markers alone (4).”
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“Following previous research (Crimmins et al., 2003; Karlamangla et al., 2002; Seeman et al., 1997, 2001, 2004), our index of allostatic load was determined empirically by adding the number of biomarkers for which an individual had a value in the highest load quartile, that is, the top quartile for…”
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Morrison, S. M., Shenassa, E. D., Mendola, P., Wu, T., & Schoendorf, K. C. (2013) · Annals of Epidemiology · doi:10.1016/j.annepidem.2013.03.006 · Cited by 47
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“Biomarker measures and AL scores A total of 10 biomarkers was used to represent functioning across cardiovascular, inflammatory, metabolic, and neuroendocrine systems (Chyu & Upchurch, 2011; Crimmins et al., 2003; McEwen & Stellar, 1993; Seeman, Crimmins, et al., 2004; Seeman et al., 2001; Seeman et al., 1997; Seeman,…”
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“Thus there is limitation of not being able to use the advantages of the continuous variables.(28) In other words, the clinical biomarkers related to the conventionally allostatic load or cumulative risk scores are affected by the high risk category, and so progressive decrease in physiologic function might not be refl…”
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“This condition is commonly referred to as ‘allostatic load’, and includes systemic impacts to cardiovascular, immune, endocrine, and metabolic function [32], as well as neurodevelopmental and cognitive effects [33,34].”
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“tive biological burden, which were found to be associated with future risk of cognitive, physical decline, and mortality among older adults.(25) Further studies linked the allostatic load index with measures of brain integrity, for example, gray matter density in old age(26) or reduced white matter integrity among ove…”
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“It occurs with long-term exposure to environmental and social stressors, leading to overaction and dysregulation, resulting in biological wear and tear (McEwen, 2004; Seeman et al., 2004; Seeman et al., 2001; Seeman et al., 1997).”
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“Over 100 studies have used a variety of AL algorithms that summarize neuroendocrine, immune, metabolic, and cardiovascular functioning [102] and predict disease better than existing approaches with single biomarkers [103,104].”
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BackgroundEffects of stress hormones on the structure and function of the human brain
Wolf, O. T. (2006) · Expert Review of Endocrinology & Metabolism · doi:10.1586/17446651.1.5.623 · Cited by 41
“With respect to aging, elevated cortisol levels are often part of the metabolic syndrome or part of several indices of chronic stress summarized within the allostatic load model [ 93 ].”
BackgroundTóth, E. E., Ihász, F., Barquín, R. R., & Szabó, A. (2023) · Journal of Aging and Physical Activity · doi:10.1123/japa.2022-0427 · Cited by 50
Allostatic load differs by sex and diet, but not age in older Japanese from the Goto Islands
Kusano, Y., Crews, D. E., Iwamoto, A., Sone, Y., Aoyagi, K., Maeda, T., & Leahy, R. (2016) · Annals of Human Biology · doi:10.3109/03014460.2015.1013985 · Cited by 36
“Using data from healthy older adults, studies (McEwen & Stellar, 1993; McEwen, 1999, 2003, 2004; Seeman et al., 1994, 1997, 2001) calculated an index of AL based upon 10 biomarkers.”
BackgroundMethodDoes Knowing Hurt? Perceiving Oneself as Overweight Predicts Future Physical Health and Well-Being
Daly, M., Robinson, E., & Sutin, A. R. (2017) · Psychological Science · doi:10.1177/0956797617696311 · Cited by 39
Zsoldos, E., Filippini, N., Mahmood, A., Mackay, C. E., Singh‐Manoux, A., Mika Kivimaki, B., Jenkinson, M., & Ebmeier, K. P. (2018) · Scientific Reports · doi:10.1038/s41598-018-24398-9 · Cited by 37
Berger, M., Taylor, S. M., Harriss, L. R., Campbell, S., Thompson, F., Jones, S., Sushames, A., Amminger, G. P., Sarnyai, Z., & McDermott, R. A. (2019) · Stress · doi:10.1080/10253890.2019.1572745 · Cited by 40
“Biomarkers for the AL index were selected based on (i) representation of several physiological systems including, neuroendocrine, immune, metabolic, and cardiovascular parameters, (ii) use in previous AL research (Juster et al., 2011; Seeman et al., 2001), and (iii) associations with disease risk.”
MethodStress, allostatic load and mental health in Indigenous Australians
Ketheesan, S., Rinaudo, M., Berger, M., Wenitong, M., Juster, R., McEwen, B. S., & Sarnyai, Z. (2020) · Stress · doi:10.1080/10253890.2020.1732346 · Cited by 46
Self-citationForgiveness and Aggression Among College Students
Webb, J. R., Dula, C. S., & Brewer, K. G. (2012) · Journal of Spirituality in Mental Health · doi:10.1080/19349637.2012.642669 · Cited by 38
Composite estimates of physiological stress, age, and diabetes in American Samoans
Crews, D. E. (2007) · American Journal of Physical Anthropology · doi:10.1002/ajpa.20612 · Cited by 32
Favourable changes in economic well-being and self-rated health among the elderly
Camacho, G. B. (2011) · Social Science & Medicine · doi:10.1016/j.socscimed.2011.02.027 · Cited by 41
Neighborhood perceptions and allostatic load: Evidence from Denmark
Pop, I. A., Rod, N. H., Christensen, U., Hansen, Å. M., Lund, R., & Dich, N. (2016) · Health & Place · doi:10.1016/j.healthplace.2016.04.010 · Cited by 39
Avilés-Santa, L. M., Heintzman, J., Lindberg, N. M., Guerrero-Preston, R. E., Ramos, K. S., Abraído-Lanza, A. L., Bull, J. C., Falcón, A., McBurnie, M. A., Moy, E. M., et al. (2017) · BMC Proceedings · doi:10.1186/s12919-017-0079-4 · Cited by 41
“Socioeconomic and cultural factors may modulate health and disease via biological mechanisms linked to epigenomic alterations [76, 77], microbiome changes [78, 79], and higher allostatic load [80].”
BackgroundPerceived Job Insecurity and Health: Do Duration and Timing Matter?
Glavin, P. (2015) · Sociological Quarterly · doi:10.1111/tsq.12087 · Cited by 38
O'Campo, P. J., Schetter, C. D., Guardino, C. M., Vance, M. R., Hobel, C. J., Ramey, S. L., & Shalowitz, M. U. (2016) · SSM - Population Health · doi:10.1016/j.ssmph.2016.10.014 · Cited by 38
“In initial studies of middle-aged and older populations (Singer & Ryff, 1999; Seeman et al., 1997), higher AL predicted greater morbidity and mortality (Karlamangla et al., 2006; Seeman et al., 2001, 2004; Gruenwald et al., 2006).”
Elevated allostatic load early in the course of schizophrenia
Savransky, A., Chiappelli, J., Fisseha, F., Wisner, K., Xiaoming, D., Mirmomen, S. M., Jones, A. D., Adhikari, B. M., Bruce, H. A., Rowland, L. M., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0299-z · Cited by 39
Greaney, J., Koffer, R., Saunders, E. F. H., Almeida, D., & Alexander, L. M. (2018) · Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease · doi:10.1161/jaha.118.010825 · Cited by 24
“Key Words: cardiovascular disease risk factors • depression • nitric oxide • vascular endothelial function D espite recent declines in prevalence, cardiovasculardisease (CVD) remains the leading cause of death and disability worldwide.1 Traditional risk factors (eg, high blood pressure, smoking, and dyslipidemia) alon…”
BackgroundResultInfluentialLeung, C. W., & ZHOU, M. S. (2020) · Nutrients · doi:10.3390/nu12051517 · Cited by 41
“Thus, allostatic load is theorized to represent the body’s cumulative physiological response to chronic stress and to account for individual variability in the appraisal of different stress exposures, which may be more relevant to predicting subsequent health outcomes than the perception of stress [34].”
BackgroundLanfear, J. H., Voegel, C. D., Binz, T. M., & Paul, R. A. (2020) · Steroids · doi:10.1016/j.steroids.2020.108712 · Cited by 37
Barboza‐Solís, C., Fantin, R., Kelly‐Irving, M., & Delpierre, C. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.08.018 · Cited by 43
“There is a growing amount of evidence that supports AL as a better predictor of morbidity and mortality (Gruenewald et al., 2006; Karlamangla et al., 2006; Seeman et al., 2001).”
BackgroundAging is a deprivation syndrome driven by a germ–soma conflict
Heininger, K. (2002) · Ageing Research Reviews · doi:10.1016/s1568-1637(02)00015-6 · Cited by 40
Savransky, A., Chiappelli, J., Rowland, L. M., Wisner, K., Shukla, D. K., Kochunov, P., & Hong, L. E. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000487 · Cited by 39
“Adherent to previously reported methodology for calculation of AL index (41), we identified the 25th and 75th percentile values of each of the 13 biomarkers for the control sample distribution.”
MethodBernecker, S. L., Williams, J. J., Caporale-Berkowitz, N. A., Wasil, A. R., & Constantino, M. J. (2020) · Journal of Medical Internet Research · doi:10.2196/17164 · Cited by 41
“In addition, a broad intervention could address the growing number of individuals with impairing subclinical symptoms or chronic stress [7], which increases the risk for mental and physical health problems [8] in addition to the direct distress they cause.”
Allostatic Load and Exposure Histories of Disadvantage
Prior, L. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18147222 · Cited by 39
Aging, Social Distancing, and COVID-19 Risk: Who is more Vulnerable and Why?
Faraji, J., & Metz, G. A. S. (2021) · Aging and Disease · doi:10.14336/ad.2021.0319 · Cited by 44
Resilience integrates concepts in aging research
Promislow, D., Anderson, R. M., Scheffer, M., Crespi, B. J., DeGregori, J. V., Harris, K., Natterson-Horowitz, B., Levine, M. E., Riolo, M. A., Schneider, D. S., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104199 · Cited by 40
“…older adults as ‘‘the absence of disability’’ (Lavretsky, 2014), focusing particularly on the effect of allostatic load on disease (McEwen, 1998), cognitive function (Juster et al., 2010), mental health (Kapczinski et al., 2008), or overall age-related physiological functions (Seeman et al., 2001).”
BackgroundInfluentialHampson, S. E., Goldberg, L. R., Vogt, T. M., Hillier, T. A., & Dubanoski, J. P. (2009) · Journal of Health Psychology · doi:10.1177/1359105308100207 · Cited by 32
Comparison of Hair Cortisol Levels and Perceived Stress in Mothers Who Deliver at Preterm and Term
Duffy, A., Schminkey, D. L., Groer, M. E., Shelton, M. M., & Dutra, S. V. O. (2018) · Biological Research For Nursing · doi:10.1177/1099800418758952 · Cited by 37
Forgiveness and health among people in outpatient physical therapy
Svalina, S. S., & Webb, J. R. (2011) · Disability and Rehabilitation · doi:10.3109/09638288.2011.607216 · Cited by 37
“For example, negative emotions, through increased allostatic load, can lead to health problems [24,25].”
BackgroundAffective and physiological responses to stress in girls at elevated risk for depression
Waugh, C. E., Muhtadie, L., Thompson, R. J., Joormann, J., & Gotlib, I. H. (2012) · Development and Psychopathology · doi:10.1017/s0954579412000235 · Cited by 42
“As noted above, like HPA-axis dysfunction, cardiovascular dysregulation is a critical component of allostatic load (Seeman et al., 2001).”
BackgroundWesterlund, H., Gustafsson, P. E., Theorell, T., Janlert, U., & Hammarström, A. (2013) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2012-202052 · Cited by 38
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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