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J Gerontol A Biol Sci Med Sci. 2018 Jul 14. doi: 10.1093/gerona/gly164. [Epub ahead of print]

Whole Blood Gene Expression Associated with Clinical Biological Age.

Author information

1
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.
2
Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
3
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
4
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
5
Section of Cardiovascular Medicine and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
6
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
7
Hebrew SeniorLife, Harvard Medical School, Boston, MA, USA.
8
Population Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
9
Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

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 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.

PMID:
30010802
DOI:
10.1093/gerona/gly164

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