The mediating role of epigenetic clocks underlying educational inequalities in mortality: a multi-cohort study

Author:

Fiorito Giovanni,Pedron Sara,Ochoa-Rosales Carolina,McCrory Cathal,Polidoro Silvia,Zhang Yan,Dugué Pierre-Antoine,Ratliff Scott,Zhao Wei,McKay Gareth J,Costa Giuseppe,Solinas Maria Giuliana,Harris Kathleen Mullan,Tumino Rosario,Grioni Sara,Ricceri Fulvio,Panico Salvatore,Brenner Hermann,Schwettmann Lars,Waldenberger Melanie,Matias-Garcia Pamela R,Peters AnnetteORCID,Hodge Allison,Giles Graham G,Schmitz Lauren L.,Levine Morgan,Smith JenniferORCID,Liu Yongmei,Kee Frank,Young Ian,McGuinness Bernadette,McKnight Amy Jayne,van Meurs Joyce,Voortman Trudy,Kenny Rose A,Vineis Paolo,Carmeli CristianORCID,

Abstract

AbstractEducational inequalities in mortality have been observed for decades, however the underlying biological mechanisms are not well known. We assessed the mediating role of altered aging of immune cells functioning captured by DNA methylation changes in blood (known as epigenetic clocks) in educational associated all-cause mortality. Data were from eight prospective population-based cohort studies, representing 13,021 participants. We found educational inequalities in mortality were larger for men than for women, estimated by hazard differences and ratios. Epigenetic clocks explained approximately 50% of educational inequalities in mortality for men, while the proportion was small 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.

Publisher

Cold Spring Harbor Laboratory

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