Early Life Adversity and the Developmental Programming of Early Childhood Telomere Biology: A Longitudinal Study of Developmental Context and Behavioral Mediators

早期生活逆境与幼儿期端粒生物学的发展规划：发展背景和行为中介的纵向研究

• 批准号: 10297293
• 负责人: PATRICIA GARRETT-PETERS
• 金额: $ 48.46万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-09 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10297293
• 关键词: Address; Adult; African American; Age; Aging; Behavioral; Biological; Biological Aging; Biological Assay; Biological Markers; Biology; Brain; Cell Aging; Cells; Child; Child Health; Child Rearing; Chromosomes; Clinical; Code; Conflict (Psychology); DNA; DNA Methylation; Development; Discrimination; Disease; Disease model; Early Intervention; Elderly; Epigenetic Process; Exposure to; Funding; Goals; Health; Health Resources; Healthcare; Heritability; Home visitation; Informal Social Control; Intervention; Investments; Length; Life; Life Cycle Stages; Link; Longitudinal Studies; Longitudinal cohort study; Low income; Measures; Mediating; Mediator of activation protein; Mother-Child Relations; Mothers; National Institute of Child Health and Human Development; Outcome; Parents; Participant; Paternal Age; Pathway interactions; Population; Poverty; Predisposition; Pregnancy; Premature Mortality; Prevalence; Prevention; Public Health; Quality of life; Race; Reporting; Research; Risk; Role; Saliva; Shapes; Stress; Time; Videotape; Visit; base; burden of illness; cost effective; critical period; disorder risk; early childhood; early experience; early life adversity; early life stress; epidemiology study; experience; genome integrity; health disparity; improved; innovation; maternal stress; mortality; novel; nutrition; obstetrical complication; postnatal; postnatal period; prenatal; preservation; prevent; preventive intervention; prospective; protein structure; psychosocial; public health relevance; sex; success; telomere

Project Summary Early life adversity is a potent predictor of health and disease burden during middle and late adulthood, as well as earlier, all-cause, and specific disease mortality. Even more disturbing, longitudinal studies suggest that experiences of early life adversity appear to be biologically embedded such that improved later life circumstances have only modest ameliorative effects. Thus, it is critical to investigate how adversity becomes biologically embedded at an early age. We propose to examine the early biological embedding of health and disease risk in young children’s telomeres, a biomarker of cellular aging. Telomeres naturally shorten with each cell replication (cellular aging) and erode most rapidly in the first years of life, reflecting a sensitive period of development. We propose a novel longitudinal study to examine the effects of prenatal and postnatal early life adversity (i.e., poverty, parent conflict, maternal stress) on accelerated biological aging, including telomere erosion and epigenetic aging clocks, across the first three years of life. We also propose a novel examination of developmental context (i.e., parenting quality) and child behavioral (i.e., self-regulation) mediators in these pathways to elucidate potential mechanisms that may contribute to the early origins of health and disease risk. Participants (n = 200) will be drawn from a prospective longitudinal cohort study funded by NICHD (Brain and Early Experience Study; R01 HD091148-01A1). Early life adversity will be assessed via maternal report at prenatal (28 week’s gestation) and postnatal home visits (6 mo). Parenting quality (sensitivity and harsh intrusiveness) will be assessed via videotaped and coded mother- child interactions at the 6-month visit. Child self-regulation will be assessed via videotaped and coded child observations at the 27- and 36- month home visits, as well as maternal report. Biospecimens (i.e., saliva) will be collected from mothers and children at the 6-, 27-, and 36-month visits and assayed for telomere length at all three time points and DNAm conversion will be performed to provide epigenetic aging clocks at the 6- and 36- month time points. The proposed study will be the first to investigate potential linkages between early life adversity, parenting quality, child self-regulation, and biological aging during this critical period in early childhood when telomeres are eroding most rapidly and may be most susceptible to environmental input. Our long-term goal is to determine how early adversity becomes biologically embedded in early childhood in order to prevent or mitigate risk to later health and wellness. Findings will provide important information to help in the development and/or optimization of early risk-mitigating intervention and prevention efforts to improve the quality of life for children.

项目摘要 早期逆境是中期和晚期健康和疾病燃烧的潜在预测指标 成年，以及早先的全因和特定疾病死亡率。更令人不安， 纵向研究表明，早期冒险外观的经验在生物学上是 嵌入的使得改善的以后生活环境只会具有适度的改善作用。 这是至关重要的，研究广告在很小的时候就如何在生物学上嵌入。 我们建议检查年轻人健康和疾病风险的早期生物学嵌入 儿童端粒，细胞衰老的生物标志物。端粒自然缩短每个单元格 复制（细胞衰老）并在生命的头几年中最快侵蚀，反映了敏感的 发展时期。我们提出了一项新的纵向研究，以检查产前的影响 和产后早期生活广告（即贫穷，父母冲突，遗产压力） 生物衰老，包括端粒侵蚀和表观遗传衰老时钟，遍布前三个 生活年。我们还提出了对发展环境的新颖检查（即育儿 质量）和儿童行为（即自我调节）介导者在这些途径中 可能有助于健康和疾病风险的早期起源的潜在机制。 参与者（n = 200）将从NICHD资助的前瞻性纵向队列研究中提取 （大脑和早期经验研究； R01 HD091148-01A1）。早期的广告将被评估 通过产前（妊娠28周）和产后家庭就诊（6个月）的材料报告。育儿 质量（敏感性和侵入性）将通过录像和编码母亲进行评估 在6个月的访问中的儿童互动。儿童自我调节将通过录像和 在27个月和36个月的家庭访问以及Mater报告中进行的编码儿童观察。 将在6月，27个月和36个月的母亲和儿童中收集生物染色（即唾液） 访问并分配了所有三个时间点的端粒长度，DNAM转换将是 在6个月和36个月的时间点提供表观遗传老化时钟。 拟议的研究将是第一个调查早期生命冒险之间潜在联系的研究， 在这个关键时期，育儿质量，儿童自我调节和生物衰老 当端粒侵蚀最快的童年时期，可能最容易受到 环境输入。我们的长期目标是确定早期广告在生物学上的变化 为了防止或减轻后来的健康和保健风险，嵌入了幼儿期。 调查结果将提供重要的信息，以帮助早期开发和/或优化 风险减轻干预和预防努力，以改善儿童的生活质量。