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Summary: 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. [ABSTRACT FROM AUTHOR]

Micro RNAs (mi RNAs) regulate gene expression with emerging data suggesting mi RNAs play a role in skeletal muscle biology. We sought to examine the association of mi RNAs with grip strength in a community-based sample. Framingham Heart Study Offspring and Generation 3 participants ( n = 5668 54% women, mean age 55 years, range 24, 90 years) underwent grip strength measurement and mi RNA profiling using whole blood from fasting morning samples. Linear mixed-effects regression modeling of grip strength (kg) versus continuous mi RNA 'Cq' values and versus binary mi RNA expression was performed. We conducted an integrative mi RNA- mRNA coexpression analysis and examined the enrichment of biologic pathways for the top mi RNAs associated with grip strength. Grip strength was lower in women than in men and declined with age with a mean 44.7 (10.0) kg in men and 26.5 (6.3) kg in women. Among 299 mi RNAs interrogated for association with grip strength, 93 (31%) had FDR q value < 0.05, 54 (18%) had an FDR q value < 0.01, and 15 (5%) had FDR q value < 0.001. For almost all mi RNA-grip strength associations, increasing mi RNA concentration is associated with increasing grip strength. miR-20a-5p ( FDR q 1.8 × 10−6) had the most significant association and several among the top 15 mi RNAs had links to skeletal muscle including miR-126-3p, miR-30a-5p, and miR-30d-5p. The top associated biologic pathways included metabolism, chemokine signaling, and ubiquitin-mediated proteolysis. Our comprehensive assessment in a community-based sample of mi RNAs in blood associated with grip strength provides a framework to further our understanding of the biology of muscle strength. [ABSTRACT FROM AUTHOR]