Age‐associated micro<scp>RNA</scp> expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Abstract

Summary Recent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of micro RNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood micro RNA expression in 5221 adults and identified 127 micro RNA s that were differentially expressed by age at P &lt; 3.3 × 10 −4 (Bonferroni‐corrected). Most micro RNA s were underexpressed in older individuals. Integrative analysis of micro RNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated micro RNA s in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘micro RNA age’ that incorporated expression levels of 80 micro RNA s. Micro RNA age correlated modestly with predicted age from DNA methylation ( r = 0.3) and mRNA expression ( r = 0.2), suggesting that micro RNA age may complement mRNA and epigenetic age prediction models. We used the difference between micro RNA 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 micro RNA age prediction model based on whole‐blood micro RNA expression profiling. Age‐associated micro RNA s and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.