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

项目概要/摘要： 加速老化，或认知能力下降的早期发作和更快的速度沿着更广泛的身体衰退， 在低收入国家（LIC），老年人的健康和心理健康是一个独特但知之甚少的老龄化标志， 个人往往会面对多次反复出现的逆境。生物学和社会学相结合的研究 数据承诺对生物社会生命过程动态的关键见解，这些动态塑造了衰老过程， 加速老化和阿尔茨海默病及相关痴呆症（ADRD）。但绝大多数 关于老龄化和ADRD的生物社会研究已经在高收入国家（HIC）进行，只有16%的 与占全球人口84%的低收入和中等收入国家相比， 并表现出更高的当前和未来预测的痴呆症病例。该项目将通过收集 马拉维家庭与健康纵向研究中45岁以上成年人的基因组和表观基因组数据 （MLSFH）（N= 3，500）。MLSFH中超过25年的现有生命过程社会，背景和健康数据将被 补充了表观遗传衰老生物标志物和额外的认知纵向测量，以研究 在低收入国家背景下，影响加速老化和认知能力下降的风险和弹性因素。 由此产生的纵向生物社会MLSFH老化数据在LIC中将是唯一的，并将使我们能够追求 当前老龄化研究的两个前沿目标：目标1-生命过程逆境和表观遗传衰老 生物标志物：研究导致LIC人群加速老化的关键因素， 通过（a）评估现有的和新的衰老的表观遗传生物标志物，和（B）测试它们的 与生命过程逆境、健康行为和潜在遗传易感性的关系。目标2-表观遗传学 LIC中老年人的衰老生物标志物和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，以评估ADRD的生物社会决定因素， 低收入国家的人口正经历严重的逆境。指导这个项目的总体假设是， 来自MLSFH数据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 这些都是LIC环境所独有的，生命过程逆境的累积和协同效应， 遗传倾向将影响加速表观遗传衰老和认知功能的启动和进展。 下降该项目的总体创新是在一个罕见的生物社会研究议程的实施， 老龄化研究中的调查人群：撒哈拉以南非洲的大规模LIC队列。结果将提高 我们对衰老和认知能力下降的生物社会决定因素的理解，并阐明了 在缺乏有效卫生系统应对措施的低收入国家环境中实施健康老龄化干预措施 提高老年人的健康和生活质量。通过公开数据，一个重要的项目 我们的目标也是创造一种新的公共资源，显著提高研究人群的多样性， 全球生物社会老龄化和ADRD研究。

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.