Early Life Adversity, Cumulative Stress, Race, & Cell Aging in Midlife Women & Offspring BACKGROUND: There is an increasingly recognized role of stress in elevating disease risk, especially among women, minorities and socioeconomically disadvantaged groups. Few prospective studies follow individuals from childhood to adulthood, leaving critical unanswered questions such as which types of adversity, and life periods (childhood, adolescence, adulthood, or cumulative) have the greatest impact on biological aging and can help explain racial differences in health. We have a remarkable opportunity to examine types of lifespan stress in a longitudinal cohort of black and white women who have been followed from 10 years old. We have collected multiple sources of stress, including individual stressors (severe life events, chronic stressors, global perceived stress) and environmental stressors (neighborhood deprivation and violence). Our broad aim is to conduct a novel examination of adversity and links to current epigenomic markers (telomere length, epigenetic aging) in women and their children, and to systemic inflammation in the women. In this re- submission, we have identified archived serum samples from the womens? childhood baseline visit and are thus able to examine change in inflammation as well. These indices of biological aging each serve as a reliable predictor of early disease. METHOD: We are conducting a 30 year follow up of the prospective NHLBI Growth and Health Study (NGHS), a biracial cohort of children to examine intergenerational transmission of obesity (R01 HD073568). Black and white girls were initially followed prospectively from 10 to 20 years old and are now being enrolled at roughly 39 years old. Here we propose to assess indices of cellular aging in 590 NGHS women and their most recent (index) child. Retention of sample and adherence to blood and saliva sampling are excellent and an R56 helped us ensure our target sample size. We will assess whether lifespan stress is associated with indices of accelerated cellular aging at age 39, and for inflammation, change from childhood (Aim 1) and secondarily whether types of stress (severe events, chronic stressors, global perceptions, neighborhood deprivation) or time-periods (childhood, adolescence, adulthood) have differential or cumulative effects. We will assess whether pregnancy stress or lifespan stress is associated with offspring epigenomic markers (Aim 2), and whether race modifies these effects (Aim 3). Lastly, we will explore whether high resilience (support and self- esteem) buffers the effects of adversity. SIGNIFICANCE & INNOVATION: This will be the first prospective study to test lifespan stress predictors of three distinct indices of biological aging, each representing different pathways of aging, in a biracial cohort and to assess stress effects on offspring epigenome. This should advance our understanding of lifespan stress on aging biology. A more granular understanding of the types and timing of stress that impact aging processes is necessary for designing policies and programs that reduce socioeconomic disparities in health and aging.
Growing black/white disparities in health across generations has reached a critical juncture, and these differences may be due in part to greater stress exposures, which in turn may accelerate cellular aging processes. This study examines how different types of stress through the lifespan?such as traumatic events and chronic situations, perceptions of stress, and neighborhood deprivation-- might accelerate aging processes (as indexed by telomere length, epigenetic age, and inflammation) in a longitudinal cohort of biracial girls followed from age 10 and now 39, and whether their stress exposures also predict their offpsrings? biological aging. A better understanding of the types of stress that impact health and intergenerational transmission of risk, as well as the potentially protective effects of psychological resiliency factors such as social support, will help inform the design of policies and programs that reduce racial and socioeconomic disparities in premature aging and disease.