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

中年女性和后代的早年逆境、累积生活压力、种族和细胞衰老

• 批准号: 10390237
• 负责人: Elissa S. Epel
• 金额: $ 10.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10390237
• 关键词: 10 year old; 20 year old; Adherence; Adolescence; Adult; African American; Age; Aging; Archives; Award; Basic Science; Biological; Biological Aging; Biological Markers; Biology of Aging; Blood specimen; Buffers; C-reactive protein; Cause of Death; Cell Aging; Child; Childhood; Chronic; Clinical Sciences; DNA Methylation; Data; Discrimination; Disease; Elderly; Enrollment; Ensure; Epigenetic Process; Event; Female; Funding; Generations; Genes; Goals; Growth; Health; Individual; Inflammation; Intervention; Knowledge; Length; Leukocytes; Life; Life Stress; Link; Longevity; Longitudinal cohort; Measures; Mental Health; Methylation; Minority; National Heart, Lung, and Blood Institute; Neighborhoods; Obesity; Outcome; Participant; Pathway interactions; Perception; Phenotype; Policies; Population Research; Pregnancy; Premature aging syndrome; Process; Prospective Studies; Puberty; Public Health; Race; Research; Risk; Risk Factors; Role; Same-sex; Sample Size; Sampling; Series; Serum; Social support; Source; Statistical Data Interpretation; Stress; Testing; Time; Training; Violence; Visit; Woman; abuse neglect; base; biobehavior; biracial; career; caucasian American; cohort; deprivation; design; disorder risk; early life adversity; environmental stressor; epigenome; epigenomics; experience; follow-up; girls; health difference; health disparity; healthspan; indexing; intergenerational; middle age; novel; offspring; peer; perceived stress; programs; prospective; protective effect; psychologic; pubertal timing; racial difference; racial disparity; resilience; saliva sample; self esteem; socioeconomic disadvantage; socioeconomic disparity; stressor; systemic inflammatory response; telomere; tool; transmission process; traumatic event

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.

联系 PD/PI：Epel、Elissa 中年女性及后代的早年逆境、累积压力、种族和细胞衰老 背景：人们越来越认识到压力在增加疾病风险方面的作用，特别是在 很少有前瞻性研究针对女性、少数族裔和社会弱势群体。 从童年到成年，留下了一些关键的悬而未决的问题，例如哪些类型的逆境和生活 各个时期（童年、青春期、成年或累积）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。 我们对从 10 岁起就开始追踪的黑人和白人女性的纵向队列进行了研究。 收集了多种压力来源，包括个人压力源（严重的生活事件、慢性压力源、全球压力源） 我们的总体目标是：感知压力）和环境压力源（邻里剥夺和暴力）。 对逆境和当前表观基因组标记（端粒长度、 表观遗传衰老）对妇女及其子女的影响，以及对妇女全身炎症的影响。 提交的材料中，我们已经确定了女性童年基线访问中存档的血清样本，并且是 因此也能够检查炎症的变化，这些生物衰老指标都可以作为可靠的指标。 早期疾病的预测因子。 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， 一个混血儿童队列，用于检查肥胖的代际传播（R01 HD073568）。 最初对 10 至 20 岁的白人女孩进行前瞻性随访，现在大约在 在此，我们建议评估 590 名 NGHS 女性及其最近的细胞衰老指数。 （指数）儿童的样本保留以及血液和唾液采样的遵守情况非常好，并且为 R56。 帮助我们确保目标样本量，我们将评估寿命压力是否与指数相关。 39 岁时细胞加速老化，炎症从童年开始发生变化（目标 1），其次是炎症 压力类型（严重事件、慢性压力源、全球观念、邻里剥夺）或 我们将评估不同时间段（童年、青春期、成年）的差异或累积影响。 妊娠压力或寿命压力是否与后代表观基因组标记相关（目标 2），以及 最后，我们将探讨高复原力（支持和自我）。 尊重）缓冲逆境的影响。 意义与创新：这将是第一项测试寿命压力预测因素的前瞻性研究 在一个混血儿群体中，三个不同的生物衰老指数，每个指数代表不同的衰老途径， 评估压力对后代表观基因组的影响，这应该可以增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类型和时间有更细致的了解。 对于设计减少健康和老龄化方面的社会差距的政策和计划是必要的。

项目成果

Drive for thinness in adolescents predicts greater adult BMI in the Growth and Health Study cohort over 20 years.

在生长与健康研究队列中，青少年追求瘦身的动力预测 20 年来成年人的 BMI 会更高。

• 发表时间: 2021-12
• 作者: Laraia, Barbara A;Leung, Cindy W;Tomiyama, A Janet;Ritchie, Lorrene D;Crawford, Patricia B;Epel, Elissa S
• 通讯作者: Epel, Elissa S