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01-05-2019 | Epigenetics | MORTALITY

Oxidative stress and epigenetic mortality risk score: associations with all-cause mortality among elderly people

Authors: Xu Gao, Xīn Gào, Yan Zhang, Bernd Holleczek, Ben Schöttker, Hermann Brenner

Published in: European Journal of Epidemiology | Issue 5/2019

Abstract

Oxidative stress (OS) has been found to be related to accelerated aging and many aging-related health outcomes. Recently, an epigenetic “mortality risk score” (MS) based on whole blood DNA methylation at 10 mortality-related CpG sites has been demonstrated to be associated with all-cause mortality. This study aimed to address the association between OS and MS, and to assess and compare their performance in the prediction of all-cause mortality. For 1448 participants aged 50–75 of the German ESTHER cohort study, the MS was derived from the DNA methylation profiles measured by Illumina HumanMethylation450K Beadchip and the levels of two urinary OS markers, 8-isoprostane (8-iso) and oxidized guanine/guanosine [including 8-hydroxy-2′-deoxyguanosine (8-oxo)], were measured by ELISA kits. Associations between OS markers and the MS were evaluated by linear and ordinal logistic regression models, and their associations with all-cause mortality were examined by Cox regression models. Both OS markers were associated with the MS at baseline. The 8-iso levels and MS, but not 8-oxo levels, were associated with all-cause mortality during a median follow-up of 15.1 years. Fully-adjusted hazard ratios (95% CI) were 1.56 (1.13–2.16) for the 4th quartile of 8-iso levels compared with the 1st, 1.71 (1.27–2.29) and 2.92 (2.03–4.18) for the moderate and high MS defined by 2–5 and > 5 CpG sites with aberrant methylation compared with a MS of 0–1, respectively. After controlling for 8-iso levels, the hazard ratios of MS remained essentially unchanged while the association of 8-iso levels with mortality was attenuated. This study demonstrates that OS is highly associated with the epigenetic MS, and the latter at the same time has a higher predictive value for all-cause mortality.

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Title: Oxidative stress and epigenetic mortality risk score: associations with all-cause mortality among elderly people
Authors: Xu Gao
Xīn Gào
Yan Zhang
Bernd Holleczek
Ben Schöttker
Hermann Brenner
Publication date: 01-05-2019
Publisher: Springer Netherlands
Keyword: Epigenetics
Published in: European Journal of Epidemiology / Issue 5/2019
Print ISSN: 0393-2990
Electronic ISSN: 1573-7284
DOI: https://doi.org/10.1007/s10654-019-00493-7

At a glance: The STEP trials

Springer Medicine

Oxidative stress and epigenetic mortality risk score: associations with all-cause mortality among elderly people

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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