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

联系PD/PI：Epel，Elissa 中年妇女及其后代的早期生活逆境、累积压力、种族和细胞老化 背景：人们越来越认识到压力在增加疾病风险方面的作用，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人 从童年到成年，留下了一些关键的悬而未决的问题，比如哪些类型的逆境，以及生活 时期(童年、青春期、成年期或累积)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。我们有一个极好的机会来研究不同类型的寿命 从10岁开始跟踪调查的黑人和白人女性纵向队列中的压力。我们有 收集多个压力源，包括个人压力源(严重生活事件、慢性压力源、全球 感受到的压力)和环境压力(邻里剥夺和暴力)。我们的广泛目标是 对逆境和与当前表观基因组标记(端粒长度， 妇女及其子女的表观遗传衰老)，以及妇女的全身性炎症。在这件事上- 提交，我们已经确定了妇女童年基线访问的存档血清样本，并 因此也能够检查炎症的变化。这些生物老化的指标都是可靠的 是早期疾病的预测指标。 方法：我们正在进行一项为期30年的前瞻性NHLBI增长与健康研究(NGHS)的跟踪调查， 研究肥胖代际传播的双族儿童队列(R01 HD073568)。黑色和 白人女孩最初被跟踪的预期年龄在10岁到20岁之间，现在大约在 现年39岁。在这里，我们建议评估590名NGHS妇女及其最近的细胞老化指数 (索引)子项。样品的保留率和对血液和唾液样本的粘附性都很好，R56 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标相关 在39岁时细胞加速老化，对于炎症，从童年(目标1)到次要的变化 无论是压力类型(严重事件、慢性压力源、全球认知、邻里剥夺)还是 时间段(童年、青春期、成年期)有不同的或累积的影响。我们将评估 怀孕压力或寿命压力是否与后代表观基因组标记有关(目标2)，以及 种族是否会改变这些影响(目标3)。最后，我们将探讨高弹性(支持和自我 自尊)可以缓冲逆境的影响。 意义和创新：这将是第一项测试寿命压力预测因素的前瞻性研究 三个不同的生物老化指数，每个指数代表不同的衰老途径，在一个双种族队列中 评估应激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 这对于设计减少健康和老龄化方面的社会经济差距的政策和方案是必要的。

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.