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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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Fox, B. M., Becker, B. K., Loria, A. S., Hyndman, K. A., Jin, C., Clark, H. E., Johns, R., Yanagisawa, M., Pollock, D. M., & Pollock, J. S. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.117.007863 · Cited by 36
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BackgroundArbeev, K. G., Akushevich, I. V., Kulminski, A. M., Arbeeva, L. S., Akushevich, L., Ukraintseva, S. V., Culminskaya, I. V., & Yashin, A. I. (2009) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2009.01.023 · Cited by 35
“…physiological norms (Lewington et al., 2002; Palatini, 1999; Westin and Heath, 2005), allostasis and allostatic load (Karlamangla et al., 2006; Seeman et al., 2001), the decline in adaptive capacity with age (homeostenosis) (Lund et al., 2002; Troncale, 1996), the decline in stress resistance…”
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“Such deviations across multiple physiologic systems are characteristic for the early stages of allostatic load, prediciting biologic morbidity and mortality later on in life.(40)”
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“Left unaddressed, negative emotions can lead to health problems, both physically (see Seeman, McEwen, Rowe, & Singer, 2001 ) and mentally.”
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Delpierre, C., Barboza‐Solís, C., Torrisani, J., Darnaudéry, M., Bartley, M., Blane, D., Kelly‐Irving, M., Getz, L., Tómasdóttir, M. Ó., Roberston, T., et al. (2016) · Longitudinal and Life Course Studies · doi:10.14301/llcs.v7i1.325 · Cited by 34
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“Previous studies have indicated that greater overall levels of AL are associated with a wide range of deleterious physical and mental health outcomes (Juster et al., 2010; Mattei et al., 2010; Seeman et al., 2001).”
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“This supports the hypothesis that ALI is a better predictor of later health than single biomarkers (Seeman et al., 2001).”
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Fava, G. A., Sonino, N., Lucente, M., & Guidi, J. (2022) · Clinical Psychological Science · doi:10.1177/21677026221121601 · Cited by 38
“The metabolic syndrome is a consequence of harmful lifestyle, frequently associated with allostatic load (Seeman et al., 2001), and there is a need to prevent its occurrence as early as possible in life (Shonkoff et al., 2009).”
BackgroundBeyond Self‐Reports: Changes in Biomarkers as Predictors of Mortality
Glei, D. A., Goldman, N., Rodríguez, G., & Weinstein, M. (2014) · Population and Development Review · doi:10.1111/j.1728-4457.2014.00676.x · Cited by 29
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Kinnunen, M.-L., Kaprio, J. A., & Pulkkinen, L. (2005) · Journal of Individual Differences · doi:10.1027/1614-0001.26.1.20 · Cited by 34
“Although the secondary outcomes chosen to measure allostatic load were congruent with metabolic syndrome, well-recognized as a risk factor for cardiovascular diseases (Alberti & Zimmet, 1998), allostatic load as a summary index has predicted health better than any primary mediator or secondary outcome component alone…”
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“…DHEA-S (a functional HPA axis antagonist); plasma concentration of total glycosylated hemoglobin (glucose metabolism measure); urinary cortisol (HPA axis measure); and urinary norepinephrine and epinephrine (sympathetic nervous system activity index) (Seeman et al., 1997; Seeman et al., 2001).”
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BackgroundChange in parent-child conflict and the HPA-axis: Where should we be looking and for how long?
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“Functioning of the HPA-axis has been repeatedly identified as a key mediator in the link between stress and both health and mortality (Adam et al., 2010; Seeman et al., 2001; Sephton et al., 2000; Taylor, 2010).”
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“People become less resilient to stress because physiological aging may modify the responsivity to stress [32,33].”
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“The AL index has been developed to measure various biological dysregulations associated with chronic stress exposure, and includes cardiovascular, metabolic, endocrine and immune-inflammatory markers (Seeman et al., 2001).”
The application of allostasis and allostatic load in animal species: A scoping review
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“Poorly managed responses to stressors add to cumulative biological burdens that make the organism more vulnerable to developing diseases or exacerbating existing disease symptoms (McEwen, 2000; Seeman et al., 2001).”
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“Originally conceptualized as attributes of the stress response that influence disease processes (McEwen and Stellar, 1993), the AL framework aims to elucidate the mechanisms underlying (co)morbidity to identify individuals who are at greater risk of degeneration and mortality (Seeman et al., 2001).”
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Contextual Predictors of Cumulative Biological Risk: Segregation and Allostatic Load
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“The metabolic syndrome partly reflects allostatic load (55,59).”
BackgroundLead exposure is related to hypercortisolemic profiles and allostatic load in Brazilian older adults
Souza‐Talarico, J. N., Suchecki, D., Juster, R., Plusquellec, P., Barbosa, F., Bunscheit, V., Marcourakis, T., Matos, T. M., & LUPIEN, S. J. (2017) · Environmental Research · doi:10.1016/j.envres.2017.01.012 · Cited by 30
“Interestingly, some data showed association between DHEA-S and metabolic syndrome that is in turn associated with AL (Muller et al., 2005; Phillips et al., 2010; Seeman et al., 2001).”
Metabolic and Genetic Markers of Biological Age
Jazwinski, S. M., & Kim, S. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00064 · Cited by 34
“It is operationalized through the measurement of 10 or more biomarkers that are meant to assess several regulatory systems and processes (Seeman et al., 2001).”
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Advancing the allostatic load model: From theory to therapy
Juster, R., & Misiak, B. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106289 · Cited by 29
Yashin, A. I., Arbeev, K. G., Arbeeva, L. S., Wu, D., Akushevich, I. V., Kovtun, M., Yashkin, A. P., Kulminski, A. M., Culminskaya, I. V., Stallard, E., et al. (2015) · Biogerontology · doi:10.1007/s10522-015-9594-8 · Cited by 27
“Note that, although the notions of the effect of allostatic adaptation and allostatic load are conceptually close to those discussed in Seeman et al. (2001) and Karlamangla et al. (2006), our mathematical description looks different from theirs because it is adapted to the structure of our model.”
Soltani, H., Keim, N. L., & Laugero, K. D. (2018) · Nutrients · doi:10.3390/nu10111606 · Cited by 32
Allostatic load and stress biomarkers in a sample of community-dwelling older adults
Freire, A. D. N. F., Fernandes, J., Pereira, D. S., Gomes, C. D. S., & Guerra, R. O. (2019) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2019.104006 · Cited by 29
Definitions and Concepts of Stress
Manosso, L. M., Gasparini, C. R., Réus, G. Z., & Pavlovic, Z. M. (2022) · Springer eBooks · doi:10.1007/978-3-030-87480-3_2 · Cited by 33
Sales, J. M., Smearman, E., Swartzendruber, A. L., Brown, J. L., Brody, G. H., & DiClemente, R. J. (2014) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2014.05.005 · Cited by 33
Do multiple health events reduce resilience when compared with single events?
Morin, R. T., Galatzer‐Levy, I. R., Maccallum, F., & Bonanno, G. A. (2017) · Health Psychology · doi:10.1037/hea0000481 · Cited by 28
“Though there are many possible explanations for this finding, including inflammatory processes that impact all comorbidities (Slavich & Irwin, 2014), and heightened allostatic load (Seeman et al., 2001), it appears this group is at greatest risk.”
Allostatic load, emotional hyper‐reactivity, and functioning in individuals with bipolar disorder
Dargél, A., Volant, S., Brietzke, E. M., Étain, B., Olié, É., Azorin, J., Gard, S., Bellivier, F., Bougerol, T., Kahn, J., et al. (2020) · Bipolar Disorders · doi:10.1111/bdi.12927 · Cited by 30
Does Subjective Social Status Predict Self-Rated Health in Chinese Adults and Why?
Zou, H., Xiong, Q., & Xu, H. (2020) · Social Indicators Research · doi:10.1007/s11205-020-02445-1 · Cited by 29
Thorpe, R. J., Cobb, R. J., King, K. M., Bruce, M. A., Archibald, P., Jones, H. P., Norris, K. C., Whitfield, K. E., & Hudson, D. (2020) · Innovation in Aging · doi:10.1093/geroni/igaa047 · Cited by 29
“An allostatic load score was created by identifying participants with values in the high-risk quartile: ≤25th percentile for HDL and ≥75th percentile for all of the biomarkers (Crimmins, 2003; Geronimus et al., 2006; Seeman et al., 2001; Suh et al., 2019).”
Methodvan Houwelingen, A. H., den Elzen, W. P. J., le Cessie, S., Blom, J. W., & Gussekloo, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121013 · Cited by 28
Saban, K. L., Mathews, H. L., Bryant, F. B., O’Brien, T. E., & Janusek, L. W. (2012) · Biological Research For Nursing · doi:10.1177/1099800412439458 · Cited by 28
“The Medical Outcomes Study (MOS) Social Support Survey (Sherbourne & Stewart, 1991) was used to measure perceived availability of social support.”
MethodGenetic determination of biological age in the mennonites of the midwestern United States
Duggirala, R., Uttley, M., Williams, K., Arya, R., Blangero, J., & Crawford, M. H. (2002) · Genetic Epidemiology · doi:10.1002/gepi.1126 · Cited by 27
“…and prevalence are positively correlated with age [Norris, 1994; Stern et al., 1996; Howard et al., 1997; Doumas and Peters, 1997; Aviv, 2001]; sometimes these disease conditions, in various combinations, may occur as comorbid entities [Foley et al., 1996; Kaplan et al., 1999; Seeman et al., 2001].”
BackgroundKim, B., Samuel, L. J., Thorpe, R. J., Crews, D. C., & Szanton, S. L. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.4674 · Cited by 27
Zhou, Y., Huang, J., Zhang, P., Tong, J., Fan, F., Gou, M., Cui, Y., Luο, X., Tan, S., Wang, Z., et al. (2020) · Schizophrenia Bulletin · doi:10.1093/schbul/sbaa196 · Cited by 27
Towards integrated modeling of the long-term impacts of oil spills
Solo‐Gabriele, H. M., Fiddaman, T., Mauritzen, C., Ainsworth, C. H., Abramson, D. M., Berenshtein, I., Chassignet, E. P., Chen, S. S., Conmy, R. N., Court, C. D., et al. (2021) · Marine Policy · doi:10.1016/j.marpol.2021.104554 · Cited by 27
“Within the literature, the term allostatic load has been used to define the cumulative impacts of repeated and multiple mental health stressors in a person’s life that results in adverse mental and physical health outcomes [61,71,80,100, 101,132,138].”
BackgroundSelf-citationOates, G. R., & Schechter, M. S. (2022) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2022.2090928 · Cited by 31
Psychobiobehavioral Model for Preterm Birth in Pregnant Women in Low- and Middle-Income Countries
Premji, S., Yim, I. S., Dosani, A., Kanji, Z., Sulaiman, S., Musana, J. W., Samia, P., Shaikh, K., Letourneau, N. L., & MiGHT Group (2015) · BioMed Research International · doi:10.1155/2015/450309 · Cited by 31
“Below we discuss each concept of the model followed by implications of developing a population-based screening tool based on the psychosocial, biological, and behavioral model.”
MethodDinwiddie, G. Y., Zambrana, R. E., Doamekpor, L. A., & López, L. (2015) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph13010042 · Cited by 27
Cuevas, A. G., Trudel‐Fitzgerald, C., Cofie, L. E., Zaitsu, M., Allen, J. D., & Williams, D. R. (2019) · Cancer Causes & Control · doi:10.1007/s10552-019-01159-1 · Cited by 27
Michaels, E. K., Reeves, A. N., Thomas, M. D., Price, M. M., Hasson, R. E., Chae, D. H., & Allen, A. M. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16234759 · Cited by 29
Income Health Inequalities Among Older Persons
Evans, G. W., Wethington, E., Coleman, M., Worms, M., & Frongillo, E. A. (2007) · Journal of Aging and Health · doi:10.1177/0898264307309938 · Cited by 27
de Baca, T. C., Prather, A. A., Lin, J., Sternfeld, B., Adler, N. E., Epel, E. S., & Puterman, E. M. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0482-5 · Cited by 26
“the allostatic load model [59] and weathering hypothesis [60].”
BackgroundZamudio‐Rodríguez, A., Dartigues, J., Amieva, H., & Pérès, K. (2021) · The Journal of Frailty & Aging · doi:10.14283/jfa.2020.62 · Cited by 27
Lee, S., Ma, C., Zhang, S., Ou, F., Bainter, T. M., Niedzwiecki, D., Saltz, L. B., Mayer, R. J., Whittom, R., Hantel, A., et al. (2022) · The Oncologist · doi:10.1093/oncolo/oyab070 · Cited by 26
Resiliencia: ¿Es posible medirla e influir en ella?
Monroy-Cortés, B. G., & Cruz, L. P. (2011) · Redalyc (Universidad Autónoma del Estado de México) · Cited by 26
Krause, J. S., Saunders, L. L., DiPiro, N. D., & Reed, K. S. (2013) · Topics in Spinal Cord Injury Rehabilitation · doi:10.1310/sci1901-15 · Cited by 26
Hollar, D. (2013) · Disability and health journal · doi:10.1016/j.dhjo.2013.01.009 · Cited by 26
“and BPXDI3); (3) body mass index (BMI; unit 5 kg/m(2); BMXBMI) in place of waist: hip ratio(5,6); (4) HDL cholesterol (unit 5 mg/dL; LBDHDL or LBDHDD, depending upon survey year); (5) total cholesterol: HDL cholesterol ratio (unitless; computed by division of variable LBXTC (mg/dl) by LBDHDL or LBDHDD (mg/dl)); (6) nu…”
BackgroundMethodResultLUPIEN, S. J., Ouellet‐Morin, I., Herba, C. M., Juster, R., & McEwen, B. S. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-24493-8_1 · Cited by 29
Self-citationThe Role of Glucose Allostasis in Type 2 Diabetes
Stümvoll, M., Tataranni, P. A., & Bogardus, C. (2004) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/b:remd.0000021430.56457.2c · Cited by 25
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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