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: 10649546
• 负责人: PATRICIA GARRETT-PETERS
• 金额: $ 53.55万
• 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/10649546
• 关键词: Acceleration; 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; Mother-Child Relations; Mothers; National Institute of Child Health and Human Development; Onset of illness; 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; 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; poor health outcome; postnatal; postnatal period; prenatal; preservation; prevent; preventive intervention; prospective; protein structure; psychosocial; public health relevance; risk mitigation; 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.

项目概要 早年的逆境是中晚年健康和疾病负担的有力预测因素 成年期以及早期的全因和特定疾病死亡率更令人不安， 纵向研究表明，早年逆境的经历似乎是生物学上的 嵌入这样的情况，即改善晚年生活环境仅产生适度的改善效果。 因此，研究逆境如何在幼年时就在生物学上根深蒂固至关重要。 我们建议检查年轻人健康和疾病风险的早期生物嵌入 儿童的端粒是细胞衰老的生物标志物，端粒会随着每个细胞的自然缩短而缩短。 生命最初几年复制（细胞老化）和侵蚀最快，反映了敏感的 我们提出了一项新颖的纵向研究来检验产前的影响。 和产后早期生活逆境（即贫困、父母冲突、产妇压力）加速 生物衰老，包括端粒侵蚀和表观遗传衰老时钟，涵盖前三个 我们还提出了对发展背景（即养育子女）的新颖检查。 这些途径中的质量）和儿童行为（即自我调节）中介因素来阐明 可能有助于健康和疾病风险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抽取 （大脑和早期经历研究；R01 HD091148-01A1）将评估早期生活的逆境。 通过产前（妊娠 28 周）和产后家访（6 个月）时的产妇报告。 质量（敏感性和严酷的侵入性）将通过录像和编码的母体进行评估 将通过录像和评估儿童在 6 个月访问中的互动情况。 对 27 个月和 36 个月家访的儿童观察结果以及产妇报告进行编码。 生物样本（即唾液）将从 6、27 和 36 个月大的母亲和儿童身上采集 在所有三个时间点进行访问并测定端粒长度，DNAm 转换将 进行以提供 6 个月和 36 个月时间点的表观遗传衰老时钟。 拟议的研究将是第一个调查早期生活逆境之间潜在联系的研究， 早期这一关键时期的养育质量、儿童自我调节和生物衰老 童年时期是端粒侵蚀最快且最容易受到影响的时期 我们的长期目标是确定早期逆境如何从生物学角度演变。 融入幼儿期，以预防或减轻对以后健康和保健的风险。 研究结果将提供重要信息，以帮助早期开发和/或优化 降低风险的干预和预防工作，以改善儿童的生活质量。