Psychosocial Factors Associated With Accelerated GrimAge in Male US Military Veterans

Objective: Veterans are at high risk for health morbidities linked to premature mortality. Recently developed "epigenetic clock" algorithms, which compute intra-individual differences between biological and chronological aging, can help inform prediction of accelerated biological aging and mortality risk. To date, however, scarce research has examined potentially modifiable correlates of GrimAge, a novel epigenetic clock comprised of DNA methylation surrogates of plasma proteins and smoking pack-years associated with various morbidities and time-to-death. The objective of the study was to examine psychosocial correlates of this novel epigenetic clock. Design: Cross-sectional study. Setting: U.S. veteran population. Participants: Participants were male, European American (EA), and derived from a nationally representative sample of U.S. veterans (N =1,135, mean age = 63.3, standard deviation [SD] = 13.0). Measurements: We examined the prevalence of accelerated GrimAge and its association with a broad range of health, lifestyle, and psychosocial variables. Results: A total 18.3% of veterans had accelerated GrimAge (>= 5 years greater GrimAge than chronological age; mean = 8.4 years acceleration, SD = 2.2). Fewer days of weekly physical exercise (relative variance explained [RVE] = 27%), history of lifetime substance use disorder (RVE = 21%), greater number of lifetime traumas (RVE = 19%), lower gratitude (RVE = 13%), reduced sleep quality (RVE = 7%), lower openness to experience (RVE = 7%), and unmarried/partnered status (RVE = 6%) were independently associated with increased odds of accelerated GrimAge. Increasing numbers of these risk factors were associated with greater odds of accelerated GrimAge, with greatest likelihood of acceleration for veterans with >= 3 risk factors (weighted 21.5%). Conclusions: These results suggest that nearly 1-of-5 EA male U.S. veterans have accelerated GrimAge, and highlight a broad range of health, lifestyle, and psychosocial variables associated with accelerated GrimAge. Given that many of these factors are modifiable, these findings provide promising leads for risk stratification models of accelerated biological aging and precision medicine -based targets for interventions to mitigate risk for premature mortality in this population. (Am J Geriatr Psychiatry 2023; 31:97-109)