Abstract
DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999–2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking.
Highlights
IntroductionDNA methylation is an aging biomarker that has attracted growing attention in recent years
DNA methylation is an aging biomarker that has attracted growing attention in recent years.Tobacco smoking is a leading risk factor for many age-related diseases, including cardiopulmonary diseases and various types of cancers [1]
We systematically explored the association between self-reported and epigenetic smoking indicators and DNAmPhenoAge in whole blood samples based on an elderly cohort in eastern
Summary
DNA methylation is an aging biomarker that has attracted growing attention in recent years. Tobacco smoking is a leading risk factor for many age-related diseases, including cardiopulmonary diseases and various types of cancers [1]. By means of regulating gene expression and genome stability, that DNA methylation is associated with smoking and smoking-related diseases [2]. Smoking-related CpG sites, located in genes such as AHRR, GPR15, and F2RL3, have. Res. Public Health 2019, 16, 2356; doi:10.3390/ijerph16132356 www.mdpi.com/journal/ijerph
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