Life-course sociogenomic analysis of social inequalities in aging

Overview. In this NIAGADS application, we seek access to DNA methylation (DNAm) data for the US Health and Retirement Study (HRS) to (1) investigate how environmental and behavioral factors in middle and later life, including physical and social environmental conditions, work and retirement, family structure, and life events affect the pace of biological aging ; and (2) to develop, validate, and refine DNAm-based indices of the pace of biological aging. These activities will establish the sensitivity of metrics of biological aging to social determinants of health and furnish validated metrics of biological aging that can be deployed to evaluate the impacts of interventions targeting the biology of aging (R01AG061378), social determinants of health that we hypothesize indirectly impact the biology of aging (R01AG087158, R01AG073402) and early-life exposures that we hypothesize hasten pace of aging across the lifespan (R01AG066887).

Analysis Plan. The program of analysis for this project will include a range of activities. We will process and normalize DNAm data following methods established in our prior work. The first step will be to merge DNAm data obtained from NIAGADS with phenotypic data obtained from the HRS. We will then (1) compute indices of the pace and progress of biological aging defined in other studies, many of which are not yet available as data products from the HRS; (2) test how these indices of biological aging are related to social and physical environmental factors (e.g. socioeconomic status and social mobility, family structure, air pollution, neighborhood social environment) and investigate the extent to which they mediate environmental impacts on incidence of chronic disease, disability, and mortality as outlined in in our previous work; (3) test how these indices relate to phenotypes of aging-related decline in functional capacities and organ system integrity defined in Balachandran et al. 2024; (4) conduct discovery analysis to determine DNAm correlates and signatures of pace of aging phenotypes defined in Balachandran et al. 2024 along with related phenotypes we are currently in the process of developing.

Life-course social science links early-life social disadvantage is how social disadvantage is biologically embedded, leading to social inequalities. A hypothesis is that social disadvantage actually hastens aging. While everyone ages chronologically at the same rate, biological changes with aging may proceed faster for some than others. These changes are thought to be a root cause of disease/disability and an intervention target to extend healthy lifespan. A knowledge gap is whether social disadvantage hastens aging-related biological changes. If so, it would open opportunity to join forces between biomedical research developing interventions to slow aging and social science research to address social inequalities. Our work and that of others indicates the pace and progress of biological aging can be measured from DNA methylation. In this project, we will investigate how social determinants of health affect trajectories of biological aging with the goal of informing programs and policies to dismantle health disparities and build healthy longevity for all.