Fetal Origins of Neural and Cellular Aging

Capitalizing on a 50-year neuroimaging follow-up study of a prenatal cohort led by Jill Goldstein (Harvard Medical School), we are collaborating with the Goldstein lab to investigate whether in utero exposures accelerate chromosomal and neural indices of aging. Participants are part of a community-based sample called the New England Family Study, which originally enrolled 17,000 pregnant women from the greater Boston area. The offspring, now midlife, have been followed since 2nd trimester in utero. This large-scale population-based neuroimaging study combines structural and functional brain imaging in the adult offspring with prenatal serologic indicators of maternal-fetal stress (e.g. inflammatory cytokines and adrenal stress hormones). Current analyses are examining whether prenatal stress accelerates age-related neurodegeneration and memory circuitry dysfunction, and whether these relationships vary by sex. We are also exploring whether prenatal stress has an enduring effect on cellular aging. Animal studies provide substantial evidence that exposure to early life stress can program the developing hypothalamic-pituitary-adrenal axis and disrupt the structure and function of brain regions densely populated with stress hormone receptors. Now, for the first time, we have the unique ability to examine these relationships prospectively in humans.