Traumatic Stress and Accelerated Aging in DNA Methylation

Boston University Medical Campus, Boston MA

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Abstract

? DESCRIPTION (provided by applicant): Recent research focused on the genetics of aging suggests that biological aging is partially under epigenetic control and that deoxyribonucleic acid (DNA) methylation profiles may be an index of the epigenetic clock that is important for regulating cellular aging (e.g., Horvath, 2013). Methylation influences developmental processes and is critical for cell differentiation and adaptation to the environment; it regulates the expression of the gene by suppressing or activating gene transcription (Szyf, 2013). Several investigators have developed algorithms to use methylation profiling to index cellular age (Hannum et al., 2013; Horvath, 2013; Weidner et al., 2014). This discovery paves the way for research into the factors that may alter the rate of biological aging. This project will use multivariate data analyses to evaluate if trauma exposure and traumatic stress, as defined by posttraumatic stress disorder (PTSD) symptom severity, are associated with accelerated cellular aging using DNA methylation age as the index of cellular age. Analyses will also test if DNA methylation age mediates the association between traumatic stress and metabolic syndrome, an age-related physical health problem that has been shown to co-occur with PTSD (Bartoli et al., 2013). Additional analyses would further explore the hypothesized association between traumatic stress and DNA methylation age to evaluate if this is driven by specific biological pathways and genetic variants implicated in cellular aging. This will be accomplished using existing data drawn from two U.S. Department of Veterans Affairs samples that can be combined as a result of their shared methodologies, yielding a total sample size of 685 white, non-Hispanic participants. The first sample comprises U.S. military veterans who served in Operation Enduring or Iraqi Freedom and the second sample consists of trauma- exposed U.S. military veterans and a subset of their trauma-exposed spouses. Both samples completed structured psychiatric diagnostic interviews and provided blood samples for DNA extraction. Information on genome-wide and epigenome-wide variation was assessed on the Illumina OMNI 2.5 million and Infinium HumanMethylation450 BeadChip arrays, respectively. This project may help to characterize the adverse environmental factors that are associated with the rate of cellular aging in the methylome and to discover new molecular pathways of traumatic-stress related disease. This will help to identify those individuals at greatest risk for accelerated agin and its negative health consequences. This is a necessary first step before risk factors can be modified with the ultimate aim of improving health.