Implications of metabolism on healthy aging in African and Caucasian Americans: the Health ABC study

新陈代谢对非洲裔和白种裔美国人健康老龄化的影响：Health ABC 研究

基本信息

批准号：
10617900
负责人：
Venkatesh Locharla Murthy
金额：
$ 59.16万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10617900
关键词：
Address Adult African American African American population Age Aging American Biochemical Bioinformatics Biological Aging Biological Markers Biology of Aging Blood Vessels Body Composition Cardiovascular Diseases Cardiovascular system Caucasians Censuses Characteristics Clinical Communities Data Science Dementia Elderly Epidemiology Exhibits Freedom Functional disorder Funding Goals Health Individual Inflammation Inflammatory Insulin Resistance Interleukin-6 Investigation Life Life Cycle Stages Longevity Longitudinal Studies Machine Learning Malignant Neoplasms Measures Metabolic Metabolic Diseases Metabolic Pathway Metabolic dysfunction Metabolism Mission Molecular Morbidity - disease rate Neurocognitive Nitric Oxide Obesity Organ Outcome Oxidative Stress Pathway interactions Pattern Performance Phase Phenotype Physical Function Physical activity Physiology Pilot Projects Plant Roots Population Premature aging syndrome Preparation Psychosocial Stress Quality of life Race Research Resources Risk ST14 gene Signal Transduction Specific qualifier value Specificity Stress Structure Techniques Youth age related base biracial caucasian American circulating biomarkers cohort dietary disability emerging adult experience fitness healthy aging high risk human old age (65+)improved indexing inflammatory marker male mental state microbial middle age molecular phenotype mortality muscle strength novel prospective sarcopenia walking speed young adult

项目摘要

Project Summary Over 100 million Americans will be over age 65 years by 2060 (representing 25% of the U.S. population), with an increasing proportion of African-Americans. Understanding which Americans exhibit “exceptionally healthy aging”—an older life free of illness, disability, or functional limitation—is central to efforts to improve quality of life and resource utilization. Current investigations on “healthy aging” focus on systemic inflammatory markers (e.g., interleukin-6) or composite indices of organ/metabolic function (the “healthy aging index,” HAI), both lim- ited by a (1) lack of sensitivity for early changes in metabolism; (2) lack of specificity for molecular pathways involved in these changes; (3) absence of investigation early in adulthood (when “aging” may be reversible); (4) few studies of African-Americans, at high-risk for age-related morbidity. In preparation for this application, we applied metabolite profiling in a pilot study of nearly 300 African-American males in Health ABC, a biracial NIA study of elderly Caucasians and African-Americans, identifying metabolites associated with HAI (oxidative stress, nitric oxide signaling, gut microbial metabolism), some of which may be unique to African-Americans. Here, we hypothesize that circulating metabolites associated with multi-dimensional aging phenotypes and outcomes in older adults will define pathways of “exceptional healthy aging” that may be race-specific and dysregulated in youth at risk for “premature” aging. To address this hypothesis, we will harness two well- characterized, biracial American cohorts that span life (elderly: age 73±3 N=1312; young: CARDIA, age 32±4 N=2376; R01-HL136541). In Aim 1, we define metabolic pathways implicated in race-specific healthy aging, based on association between metabolites and validated age-related phenotypes heterogeneous by race (physical, neurocognitive function, vascular structure, body composition). We will assess determinants of iden- tified pathways, including dietary quality, physical activity, and psychosocial stress (poorer in African- Americans). In Aim 2, we identify metabolites related to “exceptionally healthy aging” in the elderly (freedom from disability, dementia, cancer, cardiovascular disease), their pathways, race-specificity, and overlap with pathways identified in Aim 1. In Aim 3, we apply machine-learning techniques to metabolites to derive a classi- fier for exceptionally healthy aging in Health ABC and apply this prediction rule to young adults in CARDIA to identify young adults at risk for unhealthy aging. We then investigate whether individuals marked for premature aging develop adverse aging phenotypes decades later (neurocognitive, physical, vascular, clinical outcome). This proposal addresses a core mission of the NIA (directly responsive to PA-17-088) by defining a metabolic basis for “exceptional healthy aging” across race and at the extremes of life. We leverage rich phenotypes within Health ABC, funded efforts within CARDIA, and a team experienced in aging epidemiology, metabolic research, and data science approaches. Successful completion of this project will furnish a rich molecular phe- notypic resource to the aging community for investigation of mechanisms and biomarkers of biological aging.

项目概要到 2060 年，将有超过 1 亿美国人年龄超过 65 岁（占美国人口的 25%），其中越来越多的非裔美国人了解哪些美国人表现出“异常健康”。 “老龄化”——没有疾病、残疾或功能限制的老年生活——是提高生活质量的核心当前对“健康老龄化”的研究重点是全身炎症标志物。（例如，白细胞介素-6）或器官/代谢功能的综合指数（“健康衰老指数”，HAI），两者均 (1) 对代谢早期变化缺乏敏感性；(2) 对分子途径缺乏特异性；参与这些变化；（3）在成年早期（“衰老”可能是可逆的）没有进行调查； (4) 对与年龄相关的发病率高风险的非裔美国人进行的研究很少。我们在一项针对混血儿健康 ABC 的近 300 名非裔美国男性的试点研究中应用了代谢物分析 NIA 对老年白种人和非裔美国人的研究，确定了与 HAI 相关的代谢物（氧化压力、一氧化氮信号传导、肠道微生物代谢），其中一些可能是非裔美国人所独有的。在这里，我们面临与多维衰老表型相关的循环代谢物和老年人的结果将定义“异常健康老龄化”的途径，该途径可能因种族而异，为了解决这一假设，我们将利用两个良好的方法：具有特征的跨越一生的美国混血儿群体（老年人：年龄 73±3 N=1312；年轻人：CARDIA，年龄 32±4 N=2376；R01-HL136541) 在目标 1 中，我们定义了与种族特定的健康衰老有关的代谢途径，基于代谢物与经验证的年龄相关表型之间的关联，该表型因种族不同而异质（身体、神经认知功能、血管结构、身体成分）我们将评估特征的决定因素。化途径，包括饮食质量、体力活动和社会心理压力（非洲人较差）在目标 2 中，我们确定了与老年人“异常健康的衰老”（自由）相关的代谢物。残疾、痴呆、癌症、心血管疾病）、其途径、种族特异性以及与确定了目标 1 中的途径。在目标 3 中，我们将机器学习技术应用于代谢物，以得出一个分类 Health ABC 中的预测规则适用于异常健康的老龄化，并将此预测规则应用于 CARDIA 中的年轻人识别有不健康衰老风险的年轻人，然后我们调查个体是否被标记为过早衰老。几十年后，衰老会产生不利的衰老表型（神经认知、身体、血管、临床结果）。该提案通过定义新陈代谢来解决 NIA 的核心使命（直接响应 PA-17-088）我们利用丰富的表型来实现跨种族和极端生活的“异常健康老龄化”。 Health ABC 内部、CARDIA 内部资助的工作以及在衰老流行病学、代谢学方面经验丰富的团队研究和数据科学方法的成功完成该项目将提供丰富的分子现象。老龄化界研究生物衰老机制和生物标志物的非典型资源。