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

项目摘要 早期生活逆境是中晚期健康和疾病负担的有力预测因素 成年期以及更早的、全因和特定疾病的死亡率。更令人不安的是， 纵向研究表明，早期生活逆境的经历似乎是从生物学上来的。 在这种情况下，改善以后的生活环境只会产生适度的改善效果。 因此，研究逆境是如何在很小的时候就在生物学上根深蒂固的，是至关重要的。 我们建议研究年轻人的健康和疾病风险的早期生物学嵌入。 儿童端粒，细胞老化的生物标记物。每个细胞的端粒都会自然缩短 复制(细胞老化)和腐蚀在生命的头几年最快，反映出一种敏感的 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 和产后早期生活逆境(即贫困、父母冲突、母亲压力)加速 生物老化，包括端粒侵蚀和表观遗传衰老时钟，跨越前三个 生命中的岁月。我们还提出了一种对发展背景(即父母教养方式)的新考察 质量)和儿童行为(即自我调节)在这些途径中的中介，以阐明 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 (大脑和早期经验研究；R01 HD091148-01A1)。早年生活中的逆境将被评估 通过产前(怀孕28周)和产后家访(6个月)的母亲报告。养育子女 质量(敏感性和苛刻的侵扰性)将通过录像和编码的母亲- 在为期6个月的访问中，孩子们的互动。儿童自律能力将通过录像带和 在27个月和36个月的家访中对儿童进行编码观察，以及产妇报告。 将在6个月、27个月和36个月时从母亲和儿童身上收集生物寄生虫(即唾液)。 所有三个时间点的访问和端粒长度分析以及dNaM转换 在6个月和36个月的时间点执行以提供表观遗传老化时钟。 这项拟议的研究将首次调查早期生活逆境与 早期关键时期的父母教养质量、儿童自我调节与生物衰老 儿童时期端粒侵蚀最快，可能最容易患上 环境投入。我们的长期目标是确定逆境在生物学上是如何形成的 嵌入在儿童早期，以防止或减轻对以后健康和健康的风险。 调查结果将提供重要信息，以帮助开发和/或优化早期 减少风险的干预和预防努力，以提高儿童的生活质量。

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.