Whole Blood Gene Expression Associated With Clinical Biological Age

Biologic age may better reflect an individuals rate of aging than chronologic age. We conducted a transcriptome-wide association study with biologic age estimated with clinical biomarkers, which included: systolic blood pressure, forced expiratory volume at 1 second (FEV1), total cholesterol, fasting glucose, C-reactive protein, and serum creatinine. We assessed the association between the difference between biologic age and chronologic age (age) and gene expression in whole blood measured using the Affymetrix Human Exon 1.0st Array. Our discovery sample included 2,163 participants from the Framingham Offspring cohort (mean age 67 9 years, 55% women). A total of 481 genes were significantly associated with age (p < 2.8 10(6)). Among them, 415 genes were validated (p < .05/481 = 1.0 10(4)) in 2,946 participants from the Framingham Third Generation cohort (mean age 46 9 years, 53% women). Many of the significant genes were involved in the ubiquitin-mediated proteolysis pathway. The replication in 414 Rotterdam Study participants (mean age 59 8, 52% women) found 104 of 415 validated genes reached nominal significance (p < .05). We identified and validated 415 genes associated with age in a community-based cohort. Future functional characterization of the biologic age-related gene network may identify targets to test for interventions to delay aging in older adults.