Substance use and epigenetic age acceleration: Associations with alcohol, tobacco, illicit drugs, and SUD severity.
Level 4 - case-series / case-control
Cross-sectional population-based observational study
PubMed 42585945 · doi:10.1016/j.drugalcdep.2026.113269
What was done
Researchers analyzed data from 2,276 adults participating in the state-representative Person-to-Person Health Interview Study in Indiana. Participants completed validated assessments covering substance use disorder (SUD) severity, clinically significant alcohol use, non-prescription and illicit opioid use, and nicotine consumption (cigarettes, vaping, hookah). Saliva samples were collected for DNA methylation profiling to calculate biological aging metrics, specifically AgeAccelGrim2 and DunedinPACE. Multivariable regression models were used to estimate associations between substance use indicators and epigenetic aging, adjusting for covariates.
What was found
Illicit opioid use was positively associated with AgeAccelGrim2 (beta = 0.417, p = 5.913e-11) and DunedinPACE (beta = 0.180, p = 0.010). Non-prescription opioid use was also positively associated with AgeAccelGrim2 (beta = 0.264, p = 1.744e-09) and DunedinPACE (beta = 0.127, p = 0.008). Continuous SUD severity showed positive associations with AgeAccelGrim2 (beta = 0.061, p = 6.608e-06) and DunedinPACE (beta = 0.039, p = 0.008). Clinically significant alcohol use was positively associated with AgeAccelGrim2 (beta = 0.177, p = 2.111e-08) but not DunedinPACE. Cigarette smoking was positively associated with both aging measures across all consumption levels. Hookah use was negatively associated with AgeAccelGrim2 at all levels but not associated with DunedinPACE. Vaping was not associated with accelerated aging when co-modeled with cigarette smoking.
Why it matters
This study demonstrates that non-prescription and illicit opioid use, alongside overall substance use disorder severity, correlate with accelerated biological aging in a representative population sample. It suggests that substance-induced biological aging extends beyond combustible tobacco to other severe substance use patterns.
Limits
The cross-sectional design cannot establish causality or determine the temporal direction between substance use and epigenetic age acceleration. DNA methylation was measured in saliva rather than blood or target organs. Data on substance use relied on self-reported interview assessments subject to reporting bias.
Cited by
- partial Smoking, getting an X-ray, consuming ultra-processed foods, excessive drinking, and frequent flying accelerate the aging process.