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Fiorito, G.* ; Pedron, S. ; Ochoa-Rosales, C.* ; McCrory, C.* ; Polidoro, S.* ; Zhang, Y.* ; Dugué, P.A.* ; Ratliff, S.* ; Zhao, W.N.* ; Mckay, G.J.* ; Costa, G.* ; Solinas, M.G.* ; Mullan Harris, K.* ; Tumino, R.* ; Grioni, S.* ; Ricceri, F.* ; Panico, S.* ; Brenner, H.* ; Schwettmann, L. ; Waldenberger, M. ; Matias-Garcia, P.R. ; Peters, A. ; Hodge, A.* ; Giles, G.G.* ; Schmitz, L.L.* ; Levine, M.* ; Smith, J.A.* ; Liu, Y.* ; Kee, F.* ; Young, I.S.* ; McGuinness, B.* ; McKnight, A.J.* ; van Meurs, J.* ; Voortman, T.* ; Kenny, R.A.* ; Vineis, P.* ; Carmeli, C.*

The role of epigenetic clocks in explaining educational inequalities in mortality: A multi-cohort study and meta-analysis.

J. Gerontol. A Biol. Sci. Med. Sci. 77, 1750-1759 (2022)
Postprint DOI PMC
Open Access Green
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 eight 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 an excess mortality from all causes of 57 deaths per 10,000 person-years (95% confidence interval (CI): 38, 76) compared to 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 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dna Methylation ; Biomarkers ; Longevity ; Social Inequalities
ISSN (print) / ISBN 1079-5006
e-ISSN 1758-535X
Journal Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Quellenangaben Volume: 77, Issue: 9, Pages: 1750-1759 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Health Economics and Health Care Management (IGM)
Institute of Epidemiology II (EPI2)
Grants University of Sassari, Italy
European Commission