Whole Blood Gene Expression Associated with Clinical Biological Age.

Background: Biologic age may better reflect an individual's rate of aging than chronologic age.

Methods: We conducted a transcriptome-wide association study with biologic age estimated with clinical biomarkers, which included: systolic blood pressure, forced expiratory volume at one 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.

Results: Our discovery sample included 2163 participants from the Framingham Offspring cohort (mean age 67±9 years, 55% women). A total of 481 genes were significantly associated with ∆age (P<2.8x10-6). Among them, 415 genes were validated (P<0.05/481=1.0x10-4) in 2946 participants from the Framingham Third Generation cohort (mean age 46± 9 years, 53% women). Many of 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 <0.05).

Conclusion: 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.