Temporal Genomics Mechanisms Underlying Disease and Aging [RNA-Seq]

Given the salient role of early-life adversity (ELA) and the resulting biological embedding in disease risk, there is a critical need to understand the mechanisms operating at multiple levels of analysis in order to promote effective clinical treatments and intervention efforts for survivors. An example for such an effort could be to utilize models of dynamic cellular markers as individual-level factors to account for variation in intervention response and clinical outcomes. Results of this study will lead to new knowledge about specific gene expression pathways in response to stress, and whether the response is moderated by previous exposure to early adversity, shorter telomere length (a marker of cellular aging) and self-report mental-health measures. Thus, the long-term effects of this study will advance our understanding on stress-related transcriptomic changes that play a downstream role in disease susceptibility and accelerated aging, with the goal of targeting specific pathways and genes for potential intervention studies and pharmacological treatments to reverse the effects of exposure to early adversity. For example, considering high failure rates for depression treatments, and in order to tailor individual interventions, identifying objective changes in stress-induced gene expression may help to predict intervention efficacy in clinical and non-clinical settings, as seen, for example, in breast and leukemia cancers. Thus, findings will have a range of impacts for basic science, intervention studies and clinical practice that will influence treatments to match the specific cellular processes operating within an individual. Testing was carried out in Penn State's Clinical Research Center (CRC). The CRC has rooms for conducting the Trier Social Stress Test (TSST) stress-task and for no-stress control condition. Participants made two visits to the CRC, one week apart, on the same day of the weekday. Sessions were scheduled from 11:00 am to 4:15 pm and four blood samples were collected at 11:30am, 12:45pm, 1:45pm and 4:15pm. We used a randomized counter-balanced order for the two sessions (i.e., TSST and control conditions where TSST started at 12:00pm) with group membership blind to the subjects and lab personnel. In the no-stress control condition, participants were instructed to sit in a room, read magazines, and to refrain from any stressful activities (e.g., cell-phone use was restricted). In total, eight samples were collected from each participant across both sessions. For full details of study protocol, please see Shalev et al., 2020, PLoS One; doi: 10.1371/journal.pone.0221310. PMCID: PMC7122782