Smoking-related DNA methylation is associated with DNA methylation phenotypic age acceleration: The veterans affairs normative aging study

Yang Yang, Xu Gao, Allan C. Just, Elena Colicino, Cuicui Wang, Brent A. Coull, Lifang Hou, Yinan Zheng, Pantel Vokonas, Joel Schwartz, Andrea A. Baccarelli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article number2356
JournalInternational journal of environmental research and public health
Issue number13
StatePublished - Jul 1 2019


  • Aging acceleration
  • Aging biomarker
  • DNA methylation phenotypic age
  • Smoking-related DNA methylation

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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