Biological Aging Across the Life Course: Harmonizing Cohort Biospecimen Archives

整个生命过程中的生物衰老：协调队列生物样本档案

• 批准号: 10361432
• 负责人: Jessica Faul
• 金额: $ 59.92万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10361432
• 关键词: Address; Adolescent; Adult; Age; Aging; Area; Biochemistry; Biological Aging; Biological Assay; Biological Markers; Birth; Blood Chemical Analysis; Blood Pressure; Body mass index; Cells; Child Welfare; Childhood; Cities; Cognition; Communities; DNA Methylation; Data; Data Set; Data Store; Detection; Disease; Disease Progression; Early Diagnosis; Elderly; Environment; Ethnic Origin; Exposure to; Family; GDF15 gene; Gene Expression; Generations; Glycosylated hemoglobin A; Health; Health and Retirement Study; Healthcare; Immune; Individual; Insulin-Like Growth Factor I; Interleukin-6; Intervention; Life; Life Cycle Stages; Link; Longevity; Longitudinal Studies; Measures; Mediating; Mental Health; Methods; Methylation; National Longitudinal Survey of Adolescent to Adult Health; Outcome; Patient Self-Report; Phenotype; Physiological; Population; Poverty; Prevalence; Prevention; Process; Production; Quality Control; RNA; Race; Research; Research Personnel; Sampling; Signal Transduction; Social Environment; Societies; Socioeconomic Status; Subgroup; Surveys; Symptoms; Testing; Trauma; age related; biobank; biological specimen archives; biomarker validation; blood-based biomarker; clinical practice; cohort; contextual factors; cost; data harmonization; demographics; family structure; insight; middle age; post gamma-globulins; pro-brain natriuretic peptide (1-76); secondary analysis; sex; social; social adversity; sociodemographics; transcriptome sequencing; traumatic event

As the US rapidly transitions into an aging society, aging-associated diseases are increasing in both prevalence and cost. Compounding this concern is evidence that cohorts entering adulthood and midlife today are less healthy than preceding generations were at those ages. The faster rate of aging among recent cohorts is cause for concern, and necessitates earlier detection of aging-associated diseases, often well before midlife. Determining the individual physiological changes linked to aging and health outcomes provides important information about influences on the aging process, as well as identifying potential areas for intervention to increase healthy lifespan and longevity. A variety of approaches to measuring physiological aging using sets of biomarkers have been suggested in recent years—but currently little is known about how they correlate with each other, how those relationships change over the life course, and to what degree the biomarkers of aging are generalizable to population subgroups (by sex, race/ethnicity, and socioeconomic status (SES)). Early life social adversities show strong and lasting associations with aging and aging-related diseases. However, a key unanswered question is the degree to which biomarkers of aging across the life course link early life context to later life health. To understand how biomarkers of aging correlate across the life course and link to SES and social context we draw upon survey and biorepository data and samples from three large nationally representative panel studies: the Health and Retirement Study (HRS; representative of US population over age 50; biomarker data for ages 51-110), the National Longitudinal Study of Adolescent to Adult Health (Add Health; representative of adolescents in grades 7-12 in 1994; biomarker data ages 24-42) and the Fragile Families and Child Wellbeing Study (FFCW; representative of birth in large US Cities 1998-2000; biomarker data ages 9-24). The harmonization of biomarkers and survey data across these three panel studies provides an unprecedented opportunity to discover how biomarkers of aging correlate over the life course and how they correlate with SES and other social contextual factors associated with aging. Aim 1 will produce harmonized data and measures for the research community from three national panel studies with special focus on biomarkers: aging blood-based biomarkers (IL-6, TNFa, CRP, GDF15, IGF-1, Cystatin C, NT-proBNP, and hbA1c), DNA methylation (Illumina EPIC chip), and gene expression (RNA Seq). Aim 2 will examine how the biomarkers of aging are distributed and correlate with each other over the life course and across several key demographics. Also, using already generated immune cell methylation (FF at ages 9 and 15) and RNA (AH age 24-32) we will predict subsequent adult biomarkers of aging. Using the harmonized survey data, Aim 3 will examine the link between biomarkers of aging and a set of contextual measures of early life and adult health phenotypes. Results will provide insight into which measures from blood chemistry, methylation, and RNA can be used to examine contextual influences on aging long before observable symptoms arise.

随着美国迅速过渡到一个衰老的社会，与衰老相关的疾病都在增加 患病率和成本。使这种担忧更加复杂的证据表明，今天进入成年和中年 在那些年龄段的几代人不如前几代人。近期队列中衰老的速度更快 是引起人们关注的原因，并且是对中年生活之前的衰老相关疾病的必要原因。 确定与衰老和健康成果相关的个人身体变化提供了重要 有关影响衰老过程的影响，以及确定干预的潜在领域 增加健康的寿命和寿命。使用一组测量身体衰老的多种方法 近年来已经提出了生物标志物，但目前对它们与之相关的知之甚少 彼此，这些关系如何在生活过程中发生变化，以及衰老的生物标志物在多大程度上变化 可以推广到人口亚组（通过性别，种族/种族和社会经济地位（SES））。早期生活 社会逆境表现出与衰老和与衰老有关的疾病的牢固和持久的联系。但是，一个钥匙 未解决的问题是整个生命过程中衰老的生物标志物的程度将早期生活背景联系起来 以后的生活健康。了解衰老的生物标志物如何在整个生活过程中相关联并链接到SES和 社会环境我们借鉴了调查和生物验证数据以及来自三个大型国家的样本 代表性小组研究：健康和退休研究（HRS；代表美国人口以上的人口 50; 51-110岁的生物标志物数据），《青少年纵向研究》（ADD） 健康; 1994年7 - 12年级的青少年代表；生物标志物数据24-42）和脆弱的 家庭和儿童健康研究（FFCW；美国大城市的出生代表1998-2000;生物标志物 数据年龄9-24）。在这三个小组研究中生物标志物和调查数据的协调提供了 一个前所未有的机会，可以发现衰老的生物标志物如何在人生过程中相关联以及他们如何 与SES和其他与衰老相关的社会背景因素相关。 AIM 1将产生和谐 研究社区的数据和措施来自三个国家小组研究，特别关注 生物标志物：基于血液的生物标志物（IL-6，TNFA，CRP，GDF15，IGF-1，Cystatin C，NT-Probnp和 HBA1C），DNA甲基化（Illumina Epic ChIP）和基因表达（RNA SEQ）。 AIM 2将检查如何 衰老的生物标志物分布并在生活过程中相互关联，并在几个关键的过程中相互关联 人口统计。同样，使用已经产生的免疫球甲基化（9和15岁的FF）和RNA（AH 年龄24-32）我们将预测随后的成人衰老生物标志物。使用协调的调查数据，AIM 3将 检查衰老的生物标志物与早期生活和成人健康的一系列环境度量之间的联系 表型。结果将提供有关血液化学，甲基化和RNA的测量方法的见解 可用于检查上下文对衰老的影响，早在可观察到的症状就会出现。