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

联系PD/PI：Epel，Elissa 中年妇女和后代的早期生活逆境，累积压力，种族和细胞衰老 背景：人们越来越认识到压力在提高疾病风险中的作用，特别是在 妇女、少数群体和社会经济弱势群体。很少有前瞻性研究跟踪个体 从童年到成年，留下关键的未回答的问题，如哪种类型的逆境， 时期（儿童期、青春期、成年期或累积期）对生物衰老的影响最大， 可以帮助解释健康方面的种族差异。我们有一个非凡的机会来研究生命的类型 从10岁开始跟踪黑人和白色妇女纵向队列的压力。我们有 收集了多种压力来源，包括个人压力源（严重生活事件，慢性压力源，全球 感知压力）和环境压力源（邻里剥夺和暴力）。我们的主要目标是 对逆境进行新的检查并与当前的表观基因组标记（端粒长度， 表观遗传老化）的妇女和他们的孩子，和全身炎症的妇女。在这场重新- 提交，我们已经确定了妇女儿童基线访视的存档血清样本， 从而也能够检查炎症的变化。这些生物老化的指标都是可靠的 早期疾病的预测。 方法：我们正在对前瞻性NHLBI生长与健康研究（NGHS）进行30年随访， 一个研究肥胖代际传递的双胞胎儿童队列（R 01 HD 073568）。黑色和 最初对10至20岁的白色女孩进行了前瞻性跟踪，现在大约在 39岁。在这里，我们建议评估590名NGHS妇女的细胞衰老指数， （索引）孩子。样本保留以及对血液和唾液采样的粘附性非常好， 帮助我们确保了目标样本量。我们将评估寿命压力是否与指数相关 39岁时加速细胞衰老，炎症从童年开始变化（目标1）， 无论是压力类型（严重事件，慢性压力源，全球感知，邻里剥夺）或 不同时期（童年、青春期、成年期）的影响不同，或有累积效应。我们将评估 妊娠压力或寿命压力是否与后代表观基因组标记相关（Aim 2），以及 种族是否会改变这些影响（目标3）。最后，我们将探讨是否高弹性（支持和自我， 自尊）缓冲逆境的影响。 意义和创新：这将是第一个前瞻性研究，以测试寿命压力的预测因素， 三个不同的生物老化指标，每个指标代表不同的老化途径，在一个双胞胎队列中， 评估压力对后代表观基因组的影响。这应该会促进我们对寿命压力的理解， 衰老生物学对影响衰老过程的压力的类型和时间的更细粒度的理解是 设计政策和方案，减少健康和老龄化方面的社会经济差距。

Contact PD/PI: Epel, Elissa 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.