No association of posttraumatic stress disorder with epigenetic aging in women at mid-life: A longitudinal cohort study

Abstract

Posttraumatic stress disorder (PTSD) is associated with mortality and increased risk of diseases of aging, but underlying mechanisms remain unclear. We examine associations of PTSD with one potential pathway, accelerated epigenetic aging. In a longitudinal cohort of trauma-exposed middle-aged women (n = 831, n observations = 1,516), we examined cross-sectional and longitudinal associations between PTSD, with and without comorbid depression, and epigenetic aging measured by six clocks at two time points approximately 13.5 years apart: Hannum, Horvath, PhenoAge, GrimAge, DunedinPoAM, and DunedinPACE. We further examined associations of 3 well-established predictors of aging and mortality also linked with PTSD, namely, body mass index (BMI), diet quality, and physical activity, with epigenetic aging. Cross-sectionally, across all six clocks, epigenetic aging in women with PTSD alone, depression alone, and co-occurring depression and PTSD did not differ from the reference group of women without PTSD or depression in analyses adjusted for age, self-reported race, cell proportions, and ancestry principal components. In longitudinal analyses, we similarly did not find any difference in change in epigenetic age over time by PTSD and depression status at baseline. Among the health factors, in cross-sectional analyses, higher BMI was significantly and consistently associated with greater epigenetic aging measured by the PhenoAge, GrimAge, DunedinPoAM, and DunedinPACE clocks, but not measured by the Hannum or Horvath clocks. Physical activity was not consistently associated with epigenetic aging measured by Hannum, Horvath, PhenoAge, or GrimAge. In analyses with the DunedinPoAm and DunedinPACE clocks, women who reported exercise equivalent to 1 or more hours/week walking had slower epigenetic aging than women with less exercise. Diet quality was not consistently associated with epigenetic aging measured by any of the clocks. Our data do not provide evidence that biological aging, as measured by any of the six epigenetic clocks, is a pathway linking PTSD with mortality and diseases of aging.