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.

随着美国迅速步入老龄化社会，与衰老相关的疾病在美国和美国都在增加 普及率和成本。令这种担忧更加复杂的是，有证据表明，如今进入成年和中年的人群 在那个年龄段，他们的健康状况不如前几代人。最近的人群衰老速度更快 令人担忧，并且需要尽早发现与衰老相关的疾病，通常是在中年之前。 确定与衰老和健康结果相关的个体生理变化具有重要意义 有关对衰老过程的影响的信息，以及确定潜在的干预领域 增加健康寿命和寿命。使用一组测量生理老化的多种方法 近年来有人提出了生物标志物，但目前人们对它们如何与疾病相关联知之甚少。 彼此之间的关系，这些关系在生命历程中如何变化，以及衰老的生物标志物在多大程度上变化 可推广到人口亚组（按性别、种族/民族和社会经济地位 (SES)）。早期生活 社会逆境与衰老和与衰老相关的疾病有着密切而持久的联系。然而，有一个关键 悬而未决的问题是，整个生命过程中衰老的生物标志物在多大程度上将早期生活背景与 以后生活健康。了解衰老的生物标志物如何在整个生命过程中相互关联并与 SES 和 我们利用来自三个大型国家的调查和生物样本库数据以及样本来分析社会背景 代表性小组研究：健康与退休研究（HRS；代表美国超龄人口） 50； 51-110 岁的生物标志物数据），国家青少年至成人健康纵向研究（添加 健康; 1994年7-12年级青少年代表；生物标志物数据年龄 24-42) 和脆弱 家庭和儿童福祉研究（FFCW；1998-2000 年美国大城市出生代表；生物标志物 数据年龄 9-24)。这三项小组研究的生物标志物和调查数据的统一提供了 这是一个前所未有的机会，可以发现衰老的生物标志物在生命过程中如何相互关联以及它们如何 与 SES 和其他与衰老相关的社会背景因素相关。目标 1 将产生协调一致的 为研究界提供的数据和措施来自三项国家小组研究，特别关注 生物标志物：衰老血液生物标志物（IL-6、TNFa、CRP、GDF15、IGF-1、胱抑素 C、NT-proBNP 和 hbA1c）、DNA 甲基化（Illumina EPIC 芯片）和基因表达（RNA Seq）。目标 2 将研究如何 衰老的生物标志物在整个生命过程中以及几个关键领域中分布并相互关联 人口统计。此外，使用已经生成的免疫细胞甲基化（9 岁和 15 岁的 FF）和 RNA（AH 24-32 岁）我们将预测随后的成人衰老生物标志物。使用统一的调查数据，目标 3 将 检查衰老生物标志物与一系列早期生命和成人健康的背景测量之间的联系 表型。结果将深入了解血液化学、甲基化和 RNA 的哪些测量可以 早在可观察到的症状出现之前就可以用来检查环境对衰老的影响。