Early Life Adversity, Cumulative Life Stress, and Cellular Aging in Midlife Women and Offspring

BACKGROUND: There is an increasingly recognized role of stress in elevating disease risk. Differences in health may be in part due to greater exposure social stressors like early childhood stressors, and unsafe neighborhoods, through accelerating biological aging at the cellular level, although this has rarely been examining longitudinally. Our aim is to conduct a novel examination of stress and its links to rate of change in markers of cellular aging among women and their offspring during important transition periods (e.g., menopause, puberty) to understand potential pathways to early chronic disease development. Females and Blacks tend to have greater exposure to stressors. We have a remarkable opportunity to re-recruit a longitudinal cohort of Black and White girls who are now midlife women in the perimenopausal period. METHOD: This renewal proposal (R01AG059677) is to conduct a 40 year follow up of the prospective NHLBI Growth and Health Study (NGHS), a cohort of children to examine the life course and intergenerational transmission of cellular aging. Black and White girls were followed prospectively from roughly 10 to 20 years old, and we re-engaged them at 40 years old, with assessments of stress, cell aging and metabolic syndrome. We propose an assessment 10 years later, to predict change in biological aging from 40 to 50 years old. We will repeat assessments of cell aging (telomere length, epigenetic clocks, inflammation) and secondarily, metabolic syndrome in 624 NGHS women and cellular aging and BMI in their children. For Aim 1, we will assess which aspects of lifecourse stress—e.g., stressful life events, perceptions of stress, and neighborhood stress, are associated with rate of accelerated cellular aging of the women at age 50, testing differential associations of childhood, midlife, and cumulative stress. Secondary analyses will use causal mediation modeling to test potential mediating roles of early menopause, and health behaviors (nutrition, sleep, exercise). For Aim 2, we will assess the extent to which maternal stress and offspring stress are associated with change in offspring cell aging and BMI, and mediating roles of early puberty and health behaviors. SIGNIFICANCE & INNOVATION: This will one of the first prospective multigenerational studies to test lifespan stress predictors of distinct indices of biological aging and to assess stress effects on offspring epigenome. Given the prospective nature and range of stress measures, it has the potential to dramatically advance our understanding of lifespan stress on aging biology, and the roles of early puberty and menopause. A more granular understanding of the types and timing of social stress that impact biological aging processes is necessary for furthering our understanding of the malleable drivers of aging, and ultimately informing programs that promote health for all groups.