Research output

Whole Blood Gene Expression Associated With Clinical Biological Age

Research output: Contribution to journalArticleAcademicpeer-review

Associated researcher

  • Lin, H.
  • Lunetta, K. L.
  • Zhao, Q.
  • Mandaviya, P.R.

  • Rong, J.
  • Benjamin, E. J.
  • Joehanes, R.
  • Levy, D.
  • van Meurs, J. B. J.
  • Larson, M. G.
  • Murabito, J. M.

Associated organisations

Abstract

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.

    Research areas

  • ARRAY, Biologic aging, Epidemiology, Gene expression, HAPLOTYPES, KINASE, MORTALITY, PRESSURE, WIDE ASSOCIATION
View graph of relations

Details

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalJournals of Gerontology Series A-Biological Sciences and Medical Sciences
Volume74
Issue number1
DOIs
Publication statusPublished - Jan 2019