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 早期生活逆境是中期和晚期健康和疾病负担的有力预测因素 成年期，以及早期，全因和特定疾病死亡率。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生物学上的， 这样，改善以后的生活环境只有适度的改善效果。 因此，研究逆境如何在幼年时期就在生物学上根深蒂固是至关重要的。 我们建议研究年轻人健康和疾病风险的早期生物嵌入 儿童的端粒，细胞衰老的生物标志物。端粒随着每个细胞自然缩短 复制（细胞老化）和侵蚀最迅速的第一年的生活，反映了一个敏感的 发展时期。我们提出了一个新的纵向研究，以检查产前的影响， 和出生后早期生活逆境（即，贫困、父母冲突、产妇压力）对加速 生物老化，包括端粒侵蚀和表观遗传老化时钟，在前三个 多年的生活。我们还提出了一种新的发展背景检查（即，育儿 质量）和儿童行为（即，自我调节）介质在这些途径，以阐明 可能导致健康和疾病风险早期起源的潜在机制。 受试者（n = 200）将从NICHD资助的前瞻性纵向队列研究中抽取 （脑和早期经验研究; R01 HD091148 - 01A1）。早期生活的逆境将被评估 通过产前（妊娠28周）和产后家访（6个月）的母亲报告。育儿 质量（敏感性和苛刻的侵入性）将通过录像和编码的母亲进行评估- 6个月访视时的儿童互动。儿童自我调节将通过录像进行评估， 在27个月和36个月的家访中对儿童进行编码观察，以及母亲报告。 生物样本（即，唾液）将在6个月、27个月和36个月时从母亲和儿童中收集 将在所有三个时间点进行访视并测定端粒长度和DNAm转化， 在6个月和36个月的时间点进行表观遗传老化时钟。 这项拟议中的研究将是第一个调查早期生活逆境， 父母的质量，儿童的自我调节，和生物老化在这一关键时期，在早期 在童年时期，端粒被侵蚀得最快， 环境投入我们的长期目标是确定早期逆境如何在生物学上变成 在幼儿期就应进行预防或减轻对以后健康和福祉的风险。 调查结果将提供重要信息，以帮助开发和/或优化早期 减轻风险的干预和预防工作，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.