Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Abstract

Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on aging at the cellular level. A newly derived tool provides an additional means to investigate cellular aging by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular aging will show increased aging. We expect that particularly in individuals that developed symptoms of post--traumatic stress disorder (PTSD) increases in these aging parameters would stand out.From an existing longitudinal cohort study, ninety--six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self--Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19--item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic aging was estimated using the DNAm age estimator procedure.The association of trauma with telomere length was in the expected direction but not significant (B=--10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p= 0.018). In concordance, trauma significantly accelerated epigenetic aging (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic aging (B=--0.10, p= 0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results.Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic aging. These findings warrant further study of a perhaps dysfunctional compensatory cellular aging reversal in PTSD.3

DNA methylation and healthy human aging

“…As the study of DNA methylation and aging develops, improvements in technology will begin to give us a better understanding of the genomic locations where these changes occur. For studies of epigenetic drift or the epigenetic clock, the integration of environmental exposures and health outcomes will be a particular challenge, though highly pertinent as exposures such as sun exposure and stress have already been shown to affect DNA methylation levels at age‐associated sites (Grönniger et al ., 2010; Tapp et al ., 2013; Boks et al ., 2014 Noreen et al ., 2014). …”

“…While environmental exposures are generally thought to be highly variable across individuals, leading to diverging epigenetic patterns or epigenetic drift, shared experiences or exposures may lead to common epigenetic changes and thus influence the epigenetic clock. For example, a longitudinal study of soldiers before and after deployment to Afghanistan showed an increase in epigenetic age associated with trauma experienced in combat (Boks et al ., 2014). However, the consistency of epigenetic clock sites across a wide variety of people implies a third effect that is suggestive of a functional or structural reason why specific sites are more likely to undergo change with age.…”

Molecular consequences of psychological stress in human aging

“…It was demonstrated, for example, that women with the highest levels of perceived stress have telomeres shorter by the equivalent of at least ten years of additional aging compared to low-stress women (Epel et al, 2004). Recently several studies have added further weight to the association between traumatic stress and telomere length (Zhang et al, 2014, Jergovic et al, 2014, Shalev et al, 2014, Boks et al, 2014 suggesting that traumatic stress has an impact on aging at the cellular level.…”

Exploring the link between depression and accelerated cellular aging: telomeres hold the key

“…However, one study evaluated male soldiers with post-traumatic stress disorder and found that the development of post-traumatic stress disorder symptoms was associated with telomere lengthening. 147 Therefore, the association between posttraumatic stress disorder and telomere length lacks consistent support from the literature.…”