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.
Recent advances in molecular medicine have yielded new insight into the cellular mechanisms underlying biological aging and have suggested that DNA methylation profiles are a reliable index of cellular age; new algorithms for estimating DNA methylation age open the door for studying the environmental factors that may impact the rate of aging. We propose to test if trauma exposure and posttraumatic stress disorder (PTSD) are associated with accelerated cellular aging in DNA methylation and to examine if accelerated cellular aging underlies the common co-occurrence of PTSD with metabolic syndrome. In so doing, we hope to better understand PTSD-related disease and help identify those who are at greatest risk for accelerated aging and its negative health consequences.
