The association between telomere length and expression of DNA repair genes as a biological trace of cumulative lifetime stress

Compromised DNA integrity, including telomere attrition, has been linked to traumatic stress and early adversity. We investigated whether cumulative lifetime stress exposure is associated with telomere length and expression of key DNA repair genes, poly (ADP-ribose) polymerase 1 (PARP1) and X-ray repair cross complementing 1 (XRCC1), across two independent cohorts. In 65 postpartum women (cohort 1), childhood maltreatment (CM) and lifetime trauma exposure (LTE) were assessed using the Childhood Trauma Questionnaire and the Posttraumatic Diagnostic Scale event checklist. In 49 refugees and immigrants (cohort 2), trauma exposure was assessed using the Clinician-Administered PTSD Scale and the Vivo Checklist of War, Detention and Torture Events. Telomere length and gene expression were quantified in peripheral blood mononuclear cells using cohort-specific standard methods. In cohort 1, shorter telomeres were associated with higher PARP1 expression specifically in women with both CM and LTE, but not in those with lower cumulative stress exposure. Given the limited variance in stress exposure in this sample, we examined whether this pattern generalizes to a cohort with substantially higher and more heterogeneous trauma exposure. In cohort 2, shorter telomeres were consistently associated with higher expression of both PARP1 and XRCC1. These converging findings across independent cohorts suggest that cumulative lifetime stress exposure may be linked to altered DNA repair activity in the context of telomere maintenance, consistent with a model of stress-related allostatic load. While interpretation is limited by small sample sizes and methodological differences between cohorts, future studies in larger, longitudinal, and methodologically harmonized samples are needed to clarify underlying mechanisms and directionality.