Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits |
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Authors: | Tianxiao Huan George Chen Chunyu Liu Anindya Bhattacharya Jian Rong Brian H Chen Sudha Seshadri Kahraman Tanriverdi Jane E Freedman Martin G Larson Joanne M Murabito Daniel Levy |
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Institution: | 1. The Framingham Heart Study, Framingham, MA, USA;2. The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA;3. Department of Computer Science and Engineering, University of California, San Diego, CA, USA;4. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA;5. Longitudinal Studies Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA;6. Department of Medicine, Section 7. of General Internal Medicine, Boston University School of Medicine, Boston, MA, USA;8. Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA |
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Abstract: | Recent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10?4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10?5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases. |
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Keywords: | aging cardiometabolic traits methylation microRNA mortality
mRNA
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