Rivas Donato A, Lessard Sarah J, Rice Nicholas P, Lustgarten Michael S, So Kawai, Goodyear Laurie J, Parnell Laurence D, Fielding Roger A
Nutrition, Exercise Physiology, and Sarcopenia Laboratory and
Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
FASEB J. 2014 Sep;28(9):4133-47. doi: 10.1096/fj.14-254490. Epub 2014 Jun 13.
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.
老年人通过抗阻运动（RE）诱导肌肉肥大的能力下降，这可能导致与年龄相关的肌肉质量和功能丧失，即肌肉减少症。我们测试了一个新的假设，即微小RNA（miRNA）失调可能导致随着年龄增长肌肉可塑性降低。在年轻（YNG）和老年（OLD）男性进行一次急性抗阻运动后，对其骨骼肌蛋白质编码基因和miRNA进行表达谱分析。21种miRNA在YNG男性中因抗阻运动而改变，而在OLD男性中未观察到抗阻运动诱导的miRNA表达变化。OLD男性中这种显著的miRNA调节缺失与mRNA转录减弱有关，抗阻运动后OLD男性中只有42个基因发生改变，而YNG男性中有175个，这表明衰老肌肉对运动的适应性降低。综合生物信息学分析确定miR-126是运动转录反应和OLD男性瘦体重降低的重要调节因子。在体外对心肌细胞中miR-126水平进行调控，揭示了其对骨骼肌生长调节因子表达和胰岛素生长因子1（IGF-1）信号激活的直接影响。这项工作确定了miRNA在肌肉对合成代谢刺激适应中的机制作用，并揭示了随着年龄增长运动诱导的miRNA/mRNA调节存在显著损害。
