miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition

Authors: RIVAS, DONATO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PENG, FEI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BENARD, TOWNSEND - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SANCHEZ RAMOS DA, ADELINO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MARGOLIS, LEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: American Journal of Physiology - Cell Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/22/2021
Publication Date: 12/1/2021
Citation: Rivas, D.A., Peng, F., Benard, T., Sanchez Ramos da Silva , A., Fielding, R.A., Margolis, L. 2021. miR-19b-3p is associated with a diametric response to resistance exercise in older adults and regulates skeletal muscle anabolism via PTEN inhibition. American Journal of Physiology - Cell Physiology. 321(6):C977-C991. https://doi.org/10.1152/ajpcell.00190.2021.
DOI: https://doi.org/10.1152/ajpcell.00190.2021

Interpretive Summary: The objective of this study was to assess short non-coding RNA molecules called "microRNA." These "microRNA" are produced by fat cells and can be found in the circulation. We investigated whether differences in these circulating "microRNA" could help explain variations in the responses to strength training exercise in older adults. Study participants completed a six-month supervised strength training intervention. Study participants who gained muscle mass in response to the exercise training intervention had significantly higher levels of a microRNA named miR-19b-3p. We then went on to demonstrate in lab-raised muscle cells that miR-19b-3p could cause muscle cell growth. These data suggest that a specific microRNA, miR-19b-3p, may explain some of the variability in response to strength training in older adults.

Technical Abstract: Our laboratory has discovered that dysregulation in microRNA (miRNA) that target anabolic signaling between younger and older adults is a potential molecular mechanism resulting in age-associated decreases in skeletal muscle mass and function (sarcopenia). Whether differences in miRNA expression profiles account for inter-individual variability in exercise adaptation in older adults is unclear. Understanding paradoxical responses to anabolic stimulation and identifying the mechanisms for this inconsistency in mobility-limited older adults may provide new targets for the treatment of sarcopenia. The objective of the current study was to assess circulating miRNA expression profiles in diametric response of leg lean mass in mobility-limited older individuals after a 6 month progressive resistance exercise training intervention (PRET). Participants were dichotomized by gain (Gainers; n = 33) or loss (Losers; n = 40) of leg lean mass after PRET. Gainers signifcantly increased fat-free mass. Six miRNA (miR-1-3p, miR-19b-3p, miR-92a, miR-126, miR-133a-3p, and miR-133b) were identified to be differentially expressed between Gainers and Losers, with miR-19b-3p being the miRNA most highly associated with increases in fat-free mass. We then used a novel integrative approach to determine if differences in circulating miR-19b-3p potentially translate to augmented anabolic response in human skeletal muscle cells in vitro. Results from this analysis identified that overexpression of miR-19b-3p targeted and downregulated PTEN to facilitate increases in muscle protein synthetic rate. Together these data identify miR-19b-3p as a potent regulator of muscle anabolism that may contribute to an inter-individual response to PRET in mobility-limited older adults.