Developing Epigenetic Measurements To Forecast Long-Term Benefits of Early-Life Interventions (CIFAR CF-0249-CP22-034).

Early-life adversity a major driver of health and social problems across the life-course. Several interventions, including home-visitor programs, show potential to protect young children from lifelong damage arising from early-adversity. These interventions increase parental nurturing and prevent some early-life stress exposures. In the short- to medium-term, they benefit families and children. But longer-term outcomes vary substantially across children. A key barrier to scaling-up these programs to serve entire populations is high cost combined with uncertainty about which children get long-term benefits and which children need additional support. If early interventions prevent/reduce damaging effects of early-life adversity, these interventions should also prevent/postpone onset of chronic disease and disability. Evidence about such long-term benefits would directly address cost concerns. But testing long-term benefits is time- and cost-prohibitive; it would take decades of follow-up from randomized trials that already strain budgets. Methods are needed to test long-term benefits over shorter time scales. We recently developed two DNA methylation-based measures that together meet this need. One measure records enduring genomic changes caused by stress-hormones. The second measure quantifies the rate of biological aging, the progressive loss of system integrity that mediates age-related health decline. Together, these two measures will allow molecular-level testing of how early interventions shape human development and protect against age-related disease. Proposed research will validate measures in two multi-ethnic longitudinal studies and use measures to conduct a test of long-term effects of the established early-life intervention Nurse Family Partnership.

Featured Publication: : Graf G, Aiello AE, Caspi A, Kothari M, Liu H, Moffitt TE, Muennig P, Ryan CP, Sugden K, and Belsky DW. Educational mobility, pace of aging, and lifespan among participants in theFramingham Heart Study. JAMA Network Open.  Published online March 1, 2024