Prenatal exposure to genocide accelerates epigenetic aging in third- and fourth-generation clocks among young adults in Rwanda.

Background: Prenatal exposure genocide-related to trauma has been previously associated with increased morbidity. Whether the prenatal exposure to genocide and rape also impacts various aspects of biological regulation, including patterns of DNA methylation, remains unknown. The purpose of this study was to evaluate whether prenatal exposure to genocide-related trauma, including conception through rape, is associated with accelerated epigenetic aging, a molecular indicator of biological aging.

Methods: We used a cross-sectional dataset to evaluate whether prenatal exposure to genocide or genocidal rape, among individuals conceived during the 1994 genocide against Tutsi in Rwanda were associated with differences in age acceleration in a range of clocks (first generation: Horvath and Hannum; second generation: PhenoAge; third generation: GrimAge and DunedinPace; and fourth generation: YingDamAge and YingAdaptAge), while taking into account exposure to adverse childhood experiences (ACEs). Participants were 24 years old during the time of data collection, and we enrolled 46 female and 45 male participants. Control participants were those of Rwandan descent who did not live in Rwanda during the genocide.

Results: We show that there are no differences in age acceleration observed with first- or second-generation age clocks. However, age acceleration was associated with prenatal exposure to extreme stress for all other clocks, with the greatest acceleration observed in the genocidal rape conception group. For the YingDamAge clock, acceleration effects were strengthened after the inclusion of ACEs.

Conclusions: Our findings suggest that prenatal trauma exposure is associated with epigenetic age acceleration. Third and fourth-generation clocks may more accurately capture these relationships.