Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 77, Issue 9, Pages 1750-1759Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glac041
Keywords
Biomarkers; DNA methylation; Longevity; Social inequalities
Categories
Funding
- European Commission [633666]
- Programma Operativo Nazionale (PON), Ricerca e Innovazione 2014-2020, Attrazione e Mobilita Internazionale (AIM) [AIM1874325-2]
- 'Fondo di Ateneo per la ricerca 2019', University of Sassari, Italy
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Educational inequalities have long been associated with all-cause mortality, but the biological mechanisms behind this association are not well understood. This study examines the role of DNA methylation changes in explaining these inequalities and finds that they play a larger role in male mortality rates compared to females. The study also suggests that unhealthy lifestyles and World Health Organization risk factors contribute to the mediation of this association.
Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.
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