Epigenetic Age in Male Combat-Exposed War Veterans: Associations with Posttraumatic Stress Disorder Status.

Abstract

DNA methylation patterns change with age and can be used to derive an estimate of "epigenetic age," an indicator of biological age. Several studies have shown associations of posttraumatic stress disorder (PTSD) with worse somatic health and early mortality, raising the possibility of accelerated biological aging. This study examined associations between estimated epigenetic age and various variables in 160 male combat-exposed war veterans with (n = 79) and without PTSD (n = 81). DNA methylation was assessed in leukocyte genomic DNA using the Illumina 450K DNA methylation arrays. Epigenetic age was estimated using Horvath's epigenetic clock algorithm and Δage (epigenetic age-chronological age) was calculated. In veterans with PTSD (Δage = 3.2), Δage was on average lower compared to those without PTSD (Δage = 5.0; p = 0.02; Cohen's d = 0.42). This between-group difference was not explained by race/ethnicity, lifestyle factors or childhood trauma. Antidepressant use, however, explained part of the association. In the PTSD positive group, telomerase activity was negatively related to Δage (β = -0.35; p = 0.007). In conclusion, veterans with PTSD had significantly lower epigenetic age profiles than those without PTSD. Further, current antidepressant use and higher telomerase activity were related to relatively less epigenetic aging in veterans with PTSD, speculative of a mechanistic pathway that might attenuate biological aging-related processes in the context of PTSD.