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Title: Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling

Author
item Rivas, Donata - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Lessard, Sarah - Harvard Institute
item Rice, Nicholas - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Lustgarten, Michael - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item So, Kawai - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Goodyear, Laurie - Harvard Institute
item Parnell, Laurence
item Fielding, Roger - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/16/2014
Publication Date: 6/13/2014
Citation: Rivas, D.A., Lessard, S.J., Rice, N.P., Lustgarten, M.S., So, K., Goodyear, L.J., Parnell, L.D., Fielding, R.A. 2014. Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling. Journal of Federation of American Societies for Experimental Biology. DOI: 10.1096/fj.14-254490.

Interpretive Summary: Skeletal muscle growth capacity in response to exercise and nutrition is reduced with advancing age. ARS funded researchers at JMUSDA-HNRCA at Tufts University in Boston MA measured growth promoting (anabolic) signals and signals that breakdown (catabolic) muscle following strength training exercise in skeletal muscle from healthy young and older men. The older men had reduced growth promoting signals and higher levels of signals that caused muscle breakdown than the younger men after exercise. We also measured a specific type of genetic material called microRNAs which are small segments of RNA. These microRNA are important for the control of cellular growth. We found that several types of microRNAs were altered by exercise in young men but did not change in the older men. These data suggest that microRNAs play an important role in the adaptations of skeletal muscle to exercise and that this response is altered with aging.

Technical Abstract: Older individuals have a reduced capacity to induce muscle hypertrophy with resistance exercise (RE), which may contribute to the age-induced loss of muscle mass and function, sarcopenia. We tested the novel hypothesis that dysregulation of microRNAs (miRNAs) may contribute to reduced muscle plasticity with aging. Skeletal muscle expression profiling of protein-coding genes and miRNA was performed in younger (YNG) and older (OLD) men after an acute bout of RE. 21 miRNAs were altered by RE in YNG men, while no RE-induced changes in miRNA expression were observed in OLD men. This striking absence in miRNA regulation in OLD men was associated with blunted transcription of mRNAs, with only 42 genes altered in OLD men vs. 175 in YNG men following RE, demonstrating a reduced adaptability of aging muscle to exercise. Integrated bioinformatics analysis identified miR-126 as an important regulator of the transcriptional response to exercise and reduced lean mass in OLD men. Manipulation of miR-126 levels in myocytes, in vitro, revealed its direct effects on the expression of regulators of skeletal muscle growth and activation of insulin growth factor 1 (IGF-1) signaling. This work identifies a mechanistic role of miRNA in the adaptation of muscle to anabolic stimulation and reveals a significant impairment in exercise-induced miRNA/mRNA regulation with aging.