Jung Hwa Jin, Lee Kwang-Pyo, Milholland Brandon, Shin Yeo Jin, Kang Jae Sook, Kwon Ki-Sun, Suh Yousin
Department of Genetics, Albert Einstein College of Medicine, Bronx, New York.
Aging Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon.
J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1483-1491. doi: 10.1093/gerona/glx025.
Age-associated loss of muscle mass and function is a major cause of morbidity and mortality in the elderly adults. Muscular atrophy can also be induced by disuse associated with long-term bed rest or disease. Although miRNAs regulate muscle growth, regeneration, and aging, their potential role in acute muscle atrophy is poorly understood. Furthermore, alterations in circulating miRNA levels have been shown to occur during aging but their potential as noninvasive biomarkers for muscle atrophy remains largely unexplored. Here, we report comprehensive miRNA expression profiles by miRNA-seq analysis in tibialis anterior muscle and serum of a disuse-induced atrophy mouse model, mimicking the acute atrophy following long-term bed rest, as compared to those of young and old mice. Comparative analysis and validation studies have revealed that miR-455-3p was significantly decreased in muscle of both induced-atrophy model and old mice, whereas miR-434-3p was decreased in both serum and muscle of old mice, as compared to young mice. Furthermore, upregulation of miR-455-3p in fully differentiated C2C12 myoblasts induced a hypertrophic phenotype. These results suggest that deregulation of miR-455-3p may play a functional role in muscle atrophy and miR-434-3p could be a candidate serum biomarker of muscle aging.
与年龄相关的肌肉质量和功能丧失是老年人发病和死亡的主要原因。长期卧床休息或疾病相关的废用也可导致肌肉萎缩。尽管微小RNA（miRNA）调节肌肉生长、再生和衰老，但其在急性肌肉萎缩中的潜在作用仍知之甚少。此外，循环miRNA水平的改变已被证明在衰老过程中会发生，但其作为肌肉萎缩的非侵入性生物标志物的潜力在很大程度上仍未被探索。在此，我们通过miRNA测序分析报告了与年轻和老年小鼠相比，在模拟长期卧床休息后的急性萎缩的废用诱导萎缩小鼠模型的胫前肌和血清中的综合miRNA表达谱。比较分析和验证研究表明，与年轻小鼠相比，miR-455-3p在诱导萎缩模型和老年小鼠的肌肉中均显著降低，而miR-434-3p在老年小鼠的血清和肌肉中均降低。此外，在完全分化的C2C12成肌细胞中上调miR-455-3p可诱导肥大表型。这些结果表明，miR-455-3p的失调可能在肌肉萎缩中起作用，而miR-434-3p可能是肌肉衰老的候选血清生物标志物。
