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Structural Disadvantage in Adolescence and Biological Aging in Early Midlife
Taylor W Hargrove1,2,3, Alena Sorensen D'Alessio4,5, Sylvie Tuder5,6
1Department of Sociology, University of Maryland, College Park.
JAMA Network Open
|May 11, 2026
Summary
Adolescent exposure to structural disadvantage accelerates epigenetic aging and inflammation-related DNA methylation in early midlife. These findings highlight how early life contexts contribute to health disparities in aging.
Area of Science:
- Social Epidemiology
- Epigenetics
- Public Health
Background:
- Upstream social determinants like structural disadvantages significantly influence health and aging.
- While links between structural disadvantage and biological aging are known, the life-course emergence of these associations requires further investigation.
Purpose of the Study:
- To examine the association between adolescent structural disadvantage and epigenetic aging in early midlife.
- To assess the relationship between adolescent structural disadvantage and inflammation-related DNA methylation (DNAm).
- To determine if these associations differ by race.
Main Methods:
- Prospective cohort study using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health).
- Structural disadvantage in adolescence assessed using county-level census indicators.
- Epigenetic aging measured by 3 epigenetic clocks (PhenoAge, GrimAge2, DunedinPACE) and inflammation-related DNAm (CRP, TNF-α) analyzed via DNA methylation.
Main Results:
- Higher adolescent structural disadvantage was linked to accelerated epigenetic aging (GrimAge2, DunedinPACE) and greater C-reactive protein (CRP)-related DNAm.
- Associations persisted after adjusting for race and family socioeconomic status.
- While Black respondents showed faster epigenetic aging and greater CRP-related DNAm overall, the link between adolescent disadvantage and these outcomes was negative for Black individuals and positive for White individuals.
Conclusions:
- Early-life exposure to structural disadvantage is a significant factor in accelerated epigenetic aging and inflammation-related DNAm.
- Findings illuminate the developmental origins of health disparities in aging.
- Results inform strategies to mitigate the burden of age-related diseases.
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