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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #348226
Title: Circulating microRNA are predictive of aging and acute adaptive response to resistance exercise in men

Author
item MARGOLIS, LEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LESSARD, SARAH - Joslin Diabetes Center
item EZZYAT, YASSINE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item RIVAS, DONATO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Gerontology Biological Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/9/2016
Publication Date: 12/6/2016
Citation: Margolis, L., Lessard, S., Ezzyat, Y., Fielding, R.A., Rivas, D.A. 2016. Circulating microRNA are predictive of aging and acute adaptive response to resistance exercise in men. Journal of Gerontology Biological Science. https://doi.org/10.1093/gerona/glw243.

Interpretive Summary: Short non-coding RNA molecules (microRNA) found in circulating blood have the potential to function as novel noninvasive markers of skeletal muscle health. This investigation sought to determine the influence of aging on the amount of microRNA in blood at rest and following resistance exercise in male volunteers (young: n = 9; older: n = 9). Primary findings were that the amount of microRNA in blood from these men was significantly predictive of aging. Following resistance exercise and using advanced statistical analysis, we revealed a divergent response in 10 microRNAs in blood; those in younger individuals were upregulated and those in older individuals were downregulated. Using Ingenuity Pathway Analysis to test the relationship of microRNA in blood vs. messenger RNA in skeletal muscle, we found that the amount of microRNA in blood after exercise was indicative of a growth response in muscle in younger but not older participants. These important findings provide compelling evidence that the amount of microRNAs found in blood with aging may not only serve as a predictive biomarker but also reflects underlying molecular mechanisms resulting in age-associated declines in skeletal muscle mass, increased fat mass, and impaired ability to build muscle.

Technical Abstract: Circulating microRNA (c-miRNA) have the potential to function as novel noninvasive markers of the underlying physiological state of skeletal muscle. This investigation sought to determine the influence of aging on c-miRNA expression at rest and following resistance exercise in male volunteers (Young: n = 9; Older: n = 9). Primary findings were that fasting c-miRNA expression profiles were significantly predictive of aging, with miR-19b-3p, miR-206 and miR-486 distinguishing between age groups. Following resistance exercise, principal component analysis revealed a divergent response in expression of 10 c-miRNA, where expression profiles were upregulated in younger and downregulated in older participants. Using Ingenuity Pathway Analysis to test c-miRNA-to-mRNA interactions in skeletal muscle, it was found that response of c-miRNA to exercise was indicative of an anabolic response in younger but not older participants. These findings were corroborated with a positive association observed with the phosphorylation status of p-AktSer473 and p-S6K1Thr389 13 and expression of miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-26b-5p, miR-143-3p, and miR-195-5p. These important findings provide compelling evidence that dysregulation of c-miRNA expression with aging may not only serve as a predictive marker, but also reflect underlying molecular mechanisms resulting in age-associated declines in skeletal muscle mass, increased fat mass, and anabolic resistance.