National Institute on AgingLongitudinal Gene Expression and DNA Methylation Changes Associated with Frailty Progression in a Diverse Urban, Community-Dwelling Cohort
Frailty is characterized by reduced physiological reserve and increased vulnerability to stressors. Women, people from racial/ethnic minority communities, and low-income individuals are disproportionately burdened by frailty, yet limited studies have examined frailty pathophysiology in these populations. Dr. Pacheco and her team previously demonstrated that 11% of middle-aged individuals were frail and had significantly reduced survival, suggesting frailty in mid-life is associated with mortality. They also previously identified transcriptomic signatures in frail middle-aged individuals by race and sex. When these molecular changes first manifest and whether they persist throughout frailty pathogenesis remains unclear.
Dr. Pacheco hypothesizes that “weathering” identified in previous work by Geronimus is early onset frailty whose molecular mechanisms are influenced by the social determinants of health including race, sex, and poverty. She and her team will use RNA sequencing and the Illumina Methylation EPIC chip array to identify global transcriptomic and DNA methylation changes, respectively, associated with longitudinal frailty progression in middle-aged adults. They will investigate how demographics (race, sex, and poverty status) and social determinants of health influence longitudinal transcriptomic and epigenomic changes associated with frailty progression.
They predict transcriptomic and epigenomic profiles in middle-aged adults disproportionately affected by frailty will be more pronounced with increasing frailty progression and pathogenesis over time. This work will identify unique mechanistic pathways that underlie frailty phenotype and perhaps the onset of health disparities. It may also provide the foundation for future research to enhance early identification of individuals at risk for frailty and frailty-associated conditions.