Circulatory microRNAs are not effective biomarkers of muscle size and function in middle-aged men.

Loss of muscle size and strength with aging is a major cause of morbidity. Although muscle size and strength are measured by imaging or fiber cross-sectional staining and exercise testing, respectively, the development of circulatory biomarkers for these phenotypes would greatly simplify identification of muscle function deficits. MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene translation and, thereby, contribute to muscle phenotype. To assess circulatory miRNAs (c-miRNAs) applicability as potential biomarkers of muscular phenotypes, fasting plasma and muscle samples were obtained from 50 middle-aged healthy men [mean  (SD); age: 48.8 yr (SD 4.5); BMI: 26.6 kg/m (SD 3.3)]. RT-PCR of 38 miRNAs with known regulatory function within skeletal muscle identified four c-miRNAs (miR-221, miR-451a, miR-361, and miR-146a) related to either total body lean mass, leg lean mass, and 50% thigh cross-sectional area (CSA), but not strength. There was no relationship with the expression of these miRNAs in muscle. Six miRNAs within muscle were correlated with whole body lean mass, leg lean mass, and isometric knee extension torque (miR-133a and miR-146a), and 50% thigh CSA (miR-486, miR-208b, miR-133b, and miR-208a). Only miR-23b demonstrated a relationship between tissue and circulatory expression; however, only 10% of the variance was explained. miR-146a in both plasma and muscle was related to phenotype; however, no relationship between plasma and muscle expression was evident. A different subset of miRNAs correlated to muscle phenotype in muscle compared with plasma samples, suggesting that c-miRNA biomarkers of muscle phenotype are likely unrelated to muscle expression in healthy individuals.