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: 10017117
• 负责人: Elissa S. Epel
• 金额: $ 57.53万
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017117
• 关键词: 10 year old; 20 year old; Address; Adherence; Adolescence; Adult; African American; Age; Aging; Animals; Archives; Biological Aging; Biological Markers; Biology of Aging; Blood; Buffers; C-reactive protein; Cardiovascular Diseases; Categories; Cell Aging; Cells; Child; Childhood; Chronic; Chronic Disease; Complement; Complex; Data; Development; Diet; Discrimination; Disease; Enrollment; Ensure; Epigenetic Process; Event; Exposure to; Generations; Genetic; Genetic Load; Genome; Growth; Health; Human; Individual; Inflammation; Length; Leukocytes; Life; Life Cycle Stages; Life Stress; Link; Longevity; Longitudinal cohort; Measures; Methylation; Minority; Modeling; National Heart, Lung, and Blood Institute; Neighborhoods; Obesity; Onset of illness; Participant; Pathway interactions; Perception; Policies; Pregnancy; Premature aging syndrome; Process; Prospective Studies; Psychological Stress; Psychosocial Stress; Race; Regulation; Risk; Role; Saliva; Sample Size; Sampling; Serum; Social support; Source; Stress; Testing; Time; Violence; Visit; Woman; age related; biracial; black/white disparity; cohort; critical period; deprivation; design; disorder risk; early life adversity; early life stress; early onset; environmental stressor; epigenome; epigenomics; follow-up; girls; health difference; health disparity; indexing; intergenerational; middle age; novel; offspring; perceived stress; premature; programs; prospective; protective effect; psychologic; psychosocial; racial difference; racial disparity; recruit; resilience; response; secondary analysis; self esteem; social; socioeconomic disadvantage; socioeconomic disparity; socioeconomics; stressor; telomere; transmission process; traumatic event

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.

中年妇女和后代的早期逆境，累积压力，种族和细胞衰老 背景：压力在提升疾病风险中的作用越来越公认，尤其是在 妇女，少数民族和社会经济处于弱势群体。很少有前瞻性研究跟随个人 从童年到成年，留下关键的未解决问题，例如哪种类型的广告和生活 时期（童年，青少年，成年或累积）对生物衰老和 可以帮助解释健康的种族差异。我们有一个非凡的机会检查寿命类型 从10岁开始遵循的黑人和白人妇女的纵向队列中的压力。我们有 收集了多种压力来源，包括个人压力（严重的生活事件，慢性应激，全球 感知压力）和环境压力源（邻里剥夺和暴力）。我们的广泛目标是 对广告和指向当前表观基因组标记的链接进行新颖的研究（端粒长度， 妇女及其子女的表观遗传衰老，以及妇女的系统性炎症。在这个重新 提交，我们已经确定了妇女童年基线访问中的存档血清样本，并且 这也可以检查炎症的变化。这些生物衰老的指标都可以作为可靠的 早期疾病的预测指标。 方法：我们正在对前瞻性NHLBI增长与健康研究（NGHS）进行30年的随访， 一个混血儿群，检查肥胖的代际传播（R01 HD073568）。黑色和 白人女孩最初是从10到20岁的前瞻性追随的，现在大致被注册 39岁。在这里，我们建议评估590名NGHS妇女及其最近的细胞衰老指标 （索引）孩子。保留样品并遵守血液和唾液采样非常好，R56 帮助我们确保目标样本量。我们将评估寿命应力是否与指数相关 39岁时加速的细胞衰老，以及创新，从童年（AIM 1）和次级变化 压力类型（严重的事件，慢性压力，全球看法，邻里剥夺）还是 时间周期（童年，青少年，成年）具有差异或累积效应。我们将评估 怀孕压力或寿命应力是否与后代表观基因组标记有关（AIM 2）和 种族是否改变了这些效果（目标3）。最后，我们将探讨是否高弹性（支持和自我 尊重）缓冲冒险的影响。 意义与创新：这将是测试寿命应力预测指标的第一项前瞻性研究 生物衰老的三个不同指标，每个指标都代表混血儿组中的不同衰老途径 评估应力对后代表观基因组的影响。这应该提高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压力的类型和时机更加细致的理解是 设计减少健康和衰老社会经济差异的政策和计划所需的必要条件。