Abstract 14892: Age-associated microRNA Expression in Human Peripheral Blood is Associated With All-cause Mortality and Age-related Traits
Introduction: Recent evidence supports strong correlations between human aging and molecular signatures of DNA methylation and expression of protein-coding genes. The relations of microRNA (miRNA) expression to human aging and age-related clinical outcomes have not been characterized thoroughly.
Hypothesis: We hypothesized that differential miRNA expression will be predictive of chronological age and that age prediction based on miRNA expression is biologically meaningful and can be used as a biomarker of risk for age-related outcomes including all-cause mortality.
Methods and Results: We measured whole-blood miRNAs in 5221 individuals from the Framingham Heart Study to examine associations of miRNA expression with chronological age. We identified 127 miRNAs that were differentially expressed with age (at P<0.05, Bonferroni-corrected). Most of the age-associated miRNAs were underexpressed in older individuals. Integrative analysis of miRNA and mRNA expression revealed changes in age-associated mRNA expression that may be driven by age-associated miRNAs involved in many age-related pathways including RNA processing, translation, and immune functions. Expression levels of 80 miRNAs were incorporated into a model to predict the “miRNA age” of individuals. miRNA age was correlated with DNA methylation predicted age (r=0.3) and mRNA expression predicted age (r=0.2), suggesting that miRNA age may complement mRNA and epigenetic age prediction models and can capture unique aspects of the molecular mechanisms of aging and age-related diseases. We used the difference between miRNA age and chronological age as a biomarker of accelerated aging (Δage), and found association with all-cause mortality (hazard ratio=1.09, P=8.3x10-5) after adjusting for sex and chronological age. Δage was also associated with HDL cholesterol, blood pressure, and fasting glucose levels.
Conclusions: A significant proportion of blood-expressed miRNAs are associated with age. Age-associated miRNAs and their targets have potential uses in diagnosing, monitoring, and providing insight into accelerated aging and risk for age-related diseases.
Author Disclosures: T. Huan: None. G. Chen: None. C. Liu: None. J. Rong: None. K. Tanriverdi: None. S. Seshadri: None. J. Freedman: None. M. Larson: None. J. Murabito: None. D. Levy: None.
- © 2016 by American Heart Association, Inc.