Substance use and epigenetic age acceleration: Associations with alcohol, tobacco, illicit drugs, and SUD severity.

BACKGROUND: Prior research has not assessed whether validated measures of clinically significant alcohol use, alternative forms of nicotine consumption, opioid use, or overall substance use disorder (SUD) severity are linked to accelerated biological aging in population-based data. METHODS: We analyzed data from 2276 adults participating in the state-representative Person-to-Person Health Interview Study in Indiana. Participants completed validated assessments of SUD severity, clinically significant alcohol use, non-prescription and illicit opioid use, and nicotine use, and provided saliva samples for DNA methylation profiling. Measures of biological aging included AgeAccelGrim2 and DunedinPACE. Regression models were used to estimate associations between substance use indicators and biological aging, adjusting for covariates. RESULTS: Binary measures of illicit opioid use (β=0.417, p = 5.913e-11; β=0.180, p = 0.010) and non-prescription opioid use (β=0.264, p = 1.744e-09; 0.001; β=0.127, p = 0.008), as well as a continuous measure of SUD severity (β=0.061, p = 6.608e-06; β=0.039, p = 0.008) were positively associated with AgeAccelGrim2 and DunedinPACE, respectively. Clinically significant alcohol use (β=0.177, p = 2.111e-08) was positively associated with AgeAccelGrim2 but not DunedinPACE. The categorical measure of cigarette smoking was positively associated with both AgeAccelGrim2 and DunedinPACE at all levels of smoking, and the categorical measure of hookah use was negatively associated with AgeAccelGrim2 at all levels but not with DunedinPACE. Vaping was not associated with accelerated biological aging when included in the same model as cigarette smoking. CONCLUSIONS: Substance use, especially cigarette smoking and opioid use, is strongly linked to accelerated biological aging. Findings underscore the need for future research on mechanisms linking opioid use and vaping to accelerated biological aging.