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

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....

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Hauptverfasser: Gao, Xu (VerfasserIn) , Gao, Xin (VerfasserIn) , Schöttker, Ben (VerfasserIn) , Brenner, Hermann (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 February 2019
In: European journal of epidemiology
Year: 2019, Jahrgang: 34, Heft: 5, Pages: 451-462
ISSN:1573-7284
DOI:10.1007/s10654-019-00493-7
Online-Zugang:Verlag, Pay-per-use, Volltext: https://doi.org/10.1007/s10654-019-00493-7
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Verfasserangaben:Xu Gao, Xīn Gào, Yan Zhang, Bernd Holleczek, Ben Schöttker, Hermann Brenner

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520 |a 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. 
650 4 |a Aging 
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