Objectives—To examine the effect of the relationship between alcohol and cigarette consumption on biological aging using deoxyribonucleic acid (DNA) methylation-based indices.

Design—We examined the association between DNA methylation indices of smoking and alcohol to those for biological aging in two independent cohorts using the epigenetic “clock” provided by Hannum and colleagues.

Setting—Longitudinal studies of aging and the effect of psychosocial stress.

Participants—Publicly available genome-wide methylation data from participants in two ethnically informative cohorts (n=656 white, n=180 black).

Measurements—Deviation of biological age from chronological age as a result of smoking and alcohol consumption.

Results—Greater cigarette consumption was associated with accelerated biological aging, with strong effects evident at even low levels of exposure. In contrast, alcohol consumption was associated with a mixed effect on biological aging and pronounced nonlinear effects. At low and heavy levels of alcohol consumption, there was accelerated biological aging, whereas at intermediate levels of consumption there was a relative decelerating effect. The decelerating effects of alcohol were particularly notable at loci for which methylation increased with age.

Conclusion—These data support prior epidemiological studies indicating that moderate alcohol use is associated with healthy aging, but we urge caution in interpreting these results. Conversely, smoking has strong negative effects at all levels of consumption. These results also support the use of methylomic indices as a tool for assessing the impact of lifestyle on aging.