Early life influences on Epigenetic Aging in Mexican-American children

早期生活对墨西哥裔美国儿童表观遗传衰老的影响

• 批准号: 10152487
• 负责人: Nina T Holland
• 金额: $ 7.99万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152487
• 关键词: Acceleration; Adolescence; Adolescent; Adult; Affect; Age; Aging; Biological; Biological Aging; Biological Markers; Biological Process; Birth; Blood; Body mass index; Child; Childbirth; Childhood; Chronology; Clinical; Cohort Studies; DNA Methylation; Data; Demographic Factors; Development; Developmental Process; Disease; Education; Elderly; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Family; Gestational Age; Glucose; Growth and Development function; Health; Impaired cognition; Length; Life; Link; Lipids; Longevity; Malignant Neoplasms; Marital Status; Maternal Age; Measures; Metabolic; Methodology; Methods; Methylation; Mexican Americans; Minority; Molecular; Morbidity - disease rate; Mothers; Obesity; Outcome; Phenotype; Poverty; Pregnancy; Prevention; Proteomics; Psychosocial Factor; Questionnaires; Research; Risk; Role; Site; Skin; Smoking; Suggestion; Testing; Time; Tissues; age related; base; boys; cohort; cost efficient; farm worker; frailty; genome-wide; gestational weight gain; girls; health assessment; improved; mathematical algorithm; molecular marker; mortality; parity; predictive marker; prenatal; prenatal influence; prepregnancy; public health intervention; sex; smoking during pregnancy; social; social factors; sociodemographic factors; telomere; transcriptomics; traumatic stress

Project Summary Epigenetic clocks are highly accurate DNA methylation-based biomarkers of biological aging. DNA methylation clocks predict chronological age and have recently emerged as the most accurate molecular marker of biological age in comparison to telomere length, transcriptomic, and proteomic based estimators. Differences between epigenetic age estimates and chronological age, called epigenetic age acceleration, are biologically relevant and have been associated with all-cause mortality, morbidity and longevity. There are several epigenetic clocks which use different sets of CpG sites known to differ by age in a specific tissue (most often blood, but some apply to multiple tissue types) in combination with mathematical algorithms to compute an aggregate measure of epigenetic or DNA methylation age. These findings suggest that epigenetic age is a useful predictive marker of aging and age-associated conditions like cancer and obesity. Given that epigenetic clocks and their role in aging is a relatively young field of research, many data gaps remain. Some studies suggest that environmental and social factors may affect epigenetic clock ticking rates, potentially affecting aging and developmental processes yet data remain somewhat limited. Furthermore, few studies have been conducted in children, and while there is suggestive evidence that maternal metabolic and sociodemographic factors may influence DNA methylation age, findings have not been consistent between studies. Also, newer epigenetic clocks incorporating additional clinical parameters and improving on sensitivity and accuracy have recently been developed but not tested in children. Previously, we assessed DNA methylation profiles in children followed by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal birth cohort of farmworker families. We found significant associations of regional and site-specific DNA methylation in blood with sex, age and environmental exposures. In this proposal, we will leverage our existing DNA methylation data to examine associations of early life factors with epigenetic age acceleration in CHAMACOS children. We will calculate four different epigenetic clock estimates in blood collected from CHAMACOS children at three stages of childhood (birth, mid-childhood - 9y, and adolescence -14y). We will assess their correlation with chronological age and determine rates of epigenetic age acceleration. We will examine associations of epigenetic age acceleration with maternal factors during pregnancy like metabolic parameters, parity, age, and SES factors and child birth outcomes (gestational age and birthweight) and sex to identify early life factors that influence epigenetic age acceleration. Findings from this study will be used as the basis for an R01 proposal expanding our research on molecular mechanisms of epigenetic aging in CHAMACOS children. Understanding factors that might accelerate or slow ticking rates may strengthen our understanding of the molecular mechanisms involved in age-related conditions and help to identify early targets for prevention.

项目摘要 表观遗传时钟是高度精确的基于DNA甲基化的生物衰老生物标志物。DNA 甲基化时钟预测实足年龄，最近已成为最准确的分子生物学， 与端粒长度、转录组学和基于蛋白质组学的估计值相比，生物年龄的标记物。 表观遗传年龄估计值和实足年龄之间的差异，称为表观遗传年龄加速， 具有生物学相关性，并与全因死亡率、发病率和寿命相关。有 几个表观遗传时钟使用已知在特定组织中随年龄而不同的不同CpG位点组（大多数 通常是血液，但有些适用于多种组织类型）结合数学算法来计算 表观遗传学或DNA甲基化年龄的综合测量。这些发现表明，表观遗传年龄是一个 它是衰老和与年龄相关的疾病如癌症和肥胖症的有用预测标志物。 鉴于表观遗传时钟及其在衰老中的作用是一个相对年轻的研究领域， 保持。一些研究表明，环境和社会因素可能会影响表观遗传时钟的滴答声， 可能影响衰老和发育过程，但数据仍然有限。此外，少数 在儿童中进行了研究，虽然有暗示性证据表明，母体代谢和 社会人口因素可能影响DNA甲基化年龄，研究结果并不一致， 问题研究此外，更新的表观遗传时钟纳入了额外的临床参数，并提高了灵敏度 和准确性最近已经开发出来，但尚未在儿童中进行测试。 以前，我们评估了儿童的DNA甲基化谱，随后由健康中心 萨利纳斯母亲和儿童评估研究，农场工人纵向出生队列 家庭我们发现血液中区域和位点特异性DNA甲基化与性别、年龄 和环境暴露。在这项提案中，我们将利用现有的DNA甲基化数据来检查 CHAMACOS儿童早期生活因素与表观遗传年龄加速的关系我们将计算 在CHAMACOS儿童的三个阶段收集的血液中有四种不同的表观遗传时钟估计值， 儿童期（出生、9岁中期和14岁青春期）。我们将评估它们与时间顺序的相关性 年龄和决定表观遗传年龄加速率。我们将研究表观遗传年龄 妊娠期间母体因素（如代谢参数、产次、年龄和SES因素）加速 和婴儿出生结果（胎龄和出生体重）和性别，以确定影响婴儿出生的早期因素。 表观遗传年龄加速这项研究的结果将被用作R01提案的基础， CHAMACOS儿童表观遗传衰老的分子机制。理解因素 可能加速或减缓滴答声的频率， 参与与年龄有关的疾病，并帮助确定早期预防目标。