Whole Blood Gene Expression Associated With Clinical Biological Age

Honghuang Lin*, Kathryn L Lunetta, Qiang Zhao, Pooja R Mandaviya, Jian Rong, Emelia J Benjamin, Roby Joehanes, Daniel Levy, Joyce B J van Meurs, Martin G Larson, Joanne M Murabito

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 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.

Results: 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).

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.

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalJournals of Gerontology Series A-Biological Sciences and Medical Sciences
Issue number1
Publication statusPublished - Jan 2019


  • Biologic aging
  • Epidemiology
  • Gene expression

Cite this