Adversity, Aging and ADRD Risk among the Global Poor: A Biosocial Lifecourse Approach

全球穷人的逆境、老龄化和 ADRD 风险：生物社会生命历程方法

• 批准号: 10676400
• 负责人: Hans-Peter Kohler
• 金额: $ 248.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2029-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676400
• 关键词: Acceleration; Adult; Affect; Africa South of the Sahara; African; Age; Aging; Alcohol consumption; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Area; Behavior; Biological; Biological Aging; Biological Markers; Biology; Biosocial; Buffers; Chronology; Cognition; Cognitive; Cognitive aging; Cohort Studies; Comprehension; Country; Data; Dementia; Disparity; Disparity population; Droughts; Elderly; Energy Intake; Environmental Exposure; Epidemiology; Epigenetic Process; Evolution; Exhibits; Exposure to; Face; Family Study; Future; Gender; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genomics; Geroscience; Goals; Health; Health behavior; Health system; Heritability; Impaired cognition; Income; Individual; Indoor Air Pollution; Inequality; Intervention; Joints; Life; Life Cycle Stages; Life Expectancy; Longitudinal Studies; Malawi; Marriage Pattern; Measurement; Measures; Mediating; Mediator; Mental Health; Modeling; Modification; Morbidity - disease rate; Participant; Pathway interactions; Patient Self-Report; Phenotype; Policies; Population; Population Heterogeneity; Prevalence; Process; Protocols documentation; Public Health; Quality of life; Quasi-experiment; Recurrence; Reduce health disparities; Reproductive History; Research; Resources; Risk Factors; Role; Shapes; Siblings; Smoking; Social Environment; Social isolation; Socioeconomic Status; Testing; Training; United States National Institutes of Health; Variant; Woman; aged; burden of illness; cognitive function; cognitive testing; cohort; dementia risk; early onset; epigenetic marker; epigenomics; experience; gender difference; health data; healthy aging; human old age (65+); innovation; insight; low and middle-income countries; low income country; men; mortality; novel; novel marker; physical conditioning; predictive marker; public health relevance; resilience; resilience factor; response; social; study population; symposium

Project Summary/Abstract: Accelerated aging, or the earlier onset and faster pace of cognitive decline along with broader declines in physical and mental health, is a distinctive yet poorly understood hallmark of aging in low-income countries (LICs) where individuals are often exposed to multiple recurrent adversities. Research that integrates biological and social data promises key insights into the biosocial lifecourse dynamics that shape the aging process and contribute to accelerated aging and Alzheimer’s Disease and Related Dementia (ADRD). However, the vast majority of biosocial research on aging and ADRD has been conducted in high-income countries (HICs), with only 16% of the world’s population, compared to low-and middle-income countries, which have 84% of the global population and exhibit higher current and future projected cases of dementia. This project will help fill this gap by collecting genomic and epigenomic data on adults aged 45 plus in the Malawi Longitudinal Study of Families and Health (MLSFH) (N=3,500). Over 25 years of existing lifecourse social, contextual, and health data in MLSFH will be supplemented with epigenetic aging biomarkers and additional longitudinal measures of cognition to study the risk and resilience factors that shape the evolution of accelerated aging and cognitive decline in an LIC context. The resulting longitudinal biosocial MLSFH aging data will be unique within LICs and will allow us to pursue two aims that are at the forefront of current aging research: Aim 1–Lifecourse adversities and epigenetic aging biomarkers: Investigate critical factors contributing to accelerated aging in an LIC population with extensive lifecourse adversities by (a) evaluating existing and novel epigenetic biomarkers of aging, and (b) testing their relationship to lifecourse adversities, health behaviors, and underlying genetic predisposition. Aim 2–Epigenetic aging biomarkers and ADRD risk among older adults in an LIC: Investigate the relationship between epigenetic biomarkers and cognitive function/decline and ADRD to evaluate the biosocial determinants of ADRD in a LIC population experiencing high levels of adversities. The overall hypothesis guiding this project is that new epigenetic aging biomarkers derived from the MLSFH data will illuminate distinct biosocial pathways of aging that are unique to LIC contexts, and that the cumulative and synergistic effects of lifecourse adversities and genetic predispositions will influence the initiation and progression of accelerated epigenetic aging and cognitive decline. The overarching innovation of this project is the implementation of a biosocial research agenda in a rarely investigated population in aging research: a large-scale LIC cohort in sub-Saharan Africa. Results will enhance our understanding of the biosocial determinants of aging and cognitive decline and illuminate potential areas for healthy-aging interventions in LIC settings where the lack of effective health-system responses has been a barrier to enhancing the health and quality of life in older adults. By making data publicly available, an important project goal is also to generate a novel public resource that significantly enhances the diversity of study populations for global biosocial aging and ADRD research.

项目摘要/摘要： 加速衰老，或早期和更快的认知下降速度，以及身体的较大下降 和心理健康是在低收入国家（LIC）（LICS）的独特但鲜为人知的标志 个人通常会暴露于多次反复逆境。整合生物学和社会的研究 数据有望对塑造衰老过程并贡献的生物社会生命性动态动态的关键见解 加速衰老和阿尔茨海默氏病和相关痴呆症（ADRD）。但是，绝大多数 在高收入国家（HIC）进行了关于衰老和ADRD的生物社会研究，只有16％ 与低收入国家相比，世界的人口占全球人口的84％ 并暴露了更高的当前和未来痴呆症病例。该项目将通过收集来帮助填补这一空白 在马拉维家庭和健康的马拉维纵向研究中，有关45岁成年人的基因组和表观基因组数据 （MLSFH）（n = 3,500）。在MLSFH中，将超过25年的现有生活，情境和健康数据将是 补充表观遗传衰老的生物标志物和其他认知的纵向测量 在LIC背景下，塑造加速衰老和认知下降的进化的风险和弹性因素。 由此产生的纵向生物社会MLSFH老化数据将在LIC中是独一无二的，并且可以让我们购买 目前衰老研究的最前沿的两个目标：目标1-裂口逆境和表观遗传衰老 生物标志物：调查关键因素，导致有助于加速的LIC人群的衰老 通过（a）评估现有和新颖的表观遗传生物标志物以及（b）测试其生命的逆境 与生命的逆境，健康行为和潜在的遗传易感性的关系。目标2-景观 LIC中老年人的老化生物标志物和ADRD风险：研究表观遗传学之间的关系 生物标志物和认知功能/下降和ADRD评估ADRD的生物社会决定者 LIC人口经历高水平的逆境。总体假设指导这个项目是新的 从MLSFH数据得出的表观遗传衰老生物标志物将阐明衰老的不同生物社会途径 这是LIC上下文所独有的，以及生命性逆境的累积和协同作用 遗传倾向将影响加速表观遗传衰老和认知的倡议和进展 衰退。该项目的总体创新是在很少有生物社会研究议程的实施 调查了衰老研究的人群：撒哈拉以南非洲的大规模LIC队列。结果将增强 我们对衰老和认知下降和认知下降的生物社会决定者的理解，并照亮了潜在领域 在缺乏有效的健康系统反应的LIC环境中，健康衰老的干预措施已成为障碍 增强老年人的健康和生活质量。通过公开数据，一个重要的项目 目标还是生成一种新颖的公共资源，可显着增强研究人群的多样性 全球生物社会衰老和ADRD研究。