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

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

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.