Transcriptome-wide association study of inflammatory biologic age

Abstract

Chronic low grade inflammation is a fundamental mechanism of aging. We estimated biologic age using nine biomarkers from diverse inflammatory pathways and we hypothesized that genes associated with inflammatory biological age would provide insights into human aging. In Framingham Offspring Study participants at examination 8 (2005 to 2008), we used the Klemera-Doubal method to estimate inflammatory biologic age and we computed the difference (ΔAge) between biologic age and chronologic age. Gene expression in whole blood was measured using the Affymetrix Human Exon 1.0 ST Array. We used linear mixed effect models to test associations between inflammatory ΔAge and gene expression (dependent variable) adjusting for age, sex, imputed cell counts, and technical covariates. Our study sample included 2386 participants (mean age 67±9 years, 55% women). There were 448 genes significantly were associated with inflammatory ΔAge (P<2.8×10−6), 302 genes were positively associated and 146 genes were negatively associated. Pathway analysis among the identified genes highlighted the NOD-like receptor signaling and ubiquitin mediated proteolysis pathways. In summary, we identified 448 genes that were significantly associated with inflammatory biologic age. Future functional characterization may identify molecular interventions to delay aging and prolong healthspan in older adults.