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首页> 美国卫生研究院文献>American Journal of Physiology - Endocrinology and Metabolism >Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids
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Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids

机译：衰老在静止时以及抗性锻炼和必需氨基酸的合成代谢刺激后差异影响人骨骼肌microRNA表达

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Sarcopenia, skeletal muscle loss during aging, is associated with increased falls, fractures, morbidity, and loss of independence. MicroRNAs (miRNAs) are novel posttranscriptional regulators. The role of miRNAs in cell size regulation after an anabolic stimulus in human skeletal muscle is unknown. We hypothesized that aging would be associated with a differential expression of skeletal muscle primary miRNA (pri-miRNA) and mature miRNA (miR). To test this hypothesis, we used real-time PCR and immunoblotting before and after an anabolic stimulus (resistance exercise + ingestion of a 20-g leucine-enriched essential amino acid solution) to measure the expression of muscle-specific miRNAs (miR-1, miR-133a, and miR-206), upstream regulators (MyoD and myogenin), and downstream targets [insulin-like growth factor-I, histone deacetylase-4, myocyte enhancing factor-2, and Ras homolog enriched in brain (Rheb)] in skeletal muscle of young and older men. Muscle biopsies were obtained at baseline and 3 and 6 h after exercise. At baseline, we found pri-miRNA-1-1, -1-2, -133a-1, and -133a-2 expression elevated in older compared with young men (P < 0.05). Pri-miRNA-1-2, -133a-1, and -133a-2 were reduced at 6 h after exercise only in the young men compared with baseline, whereas pri-miRNA-206 was elevated at different postexercise time points in older and young men (P < 0.05). Compared with baseline, miR-1 was reduced only in the young men, whereas Rheb protein was increased in both age groups after the anabolic stimulus (P < 0.05). We conclude that skeletal muscle primary and mature miRNA expression in young men is readily altered by an anabolic stimulus of resistance exercise + essential amino acid ingestion. However, aging is associated with higher basal skeletal muscle primary miRNA expression and a dysregulated miRNA response after the anabolic stimulus.
机译：肌肉减少症是衰老过程中骨骼肌的丧失，与跌倒，骨折，发病率和独立性的丧失有关。 MicroRNA（miRNA）是新型的转录后调节因子。在人类骨骼肌合成代谢刺激后，miRNA在细胞大小调节中的作用尚不清楚。我们假设衰老与骨骼肌初级miRNA（pri-miRNA）和成熟miRNA（miR）的差异表达有关。为了验证这一假设，我们在合成代谢刺激之前（和之后进行抵抗运动+摄入富含20 g亮氨酸的必需氨基酸溶液）使用实时PCR和免疫印迹法来测量肌肉特异性miRNA（miR-1）的表达。 ，miR-133a和miR-206），上游调节剂（MyoD和肌生成素）和下游靶标[胰岛素样生长因子-I，组蛋白脱乙酰基酶4，肌细胞增强因子2和富含脑的Ras同源物（Rheb ）]在年轻和年长男性的骨骼肌中。在基线以及运动后3和6小时获得肌肉活检。在基线时，我们发现pri-miRNA-1-1，-1-2，-133a-1和-133a-2表达在年长男性中高于年轻男性（P <0.05）。与基线相比，仅年轻男性在运动后6 h时Pri-miRNA-1-2，-133a-1和-133a-2降低，而在老年人中，pri-miRNA-206在运动后的不同时间点升高。年轻人（P <0.05）。与基线相比，合成代谢刺激后，两个年龄组的miR-1仅在年轻男性中降低，而Rheb蛋白在两个年龄组中均升高（P <0.05）。我们得出的结论是，抵抗运动+必需氨基酸摄入的合成代谢刺激很容易改变年轻男性的骨骼肌初级和成熟miRNA表达。然而，衰老与合成代谢刺激后较高的基础骨骼肌初级miRNA表达和miRNA反应失调有关。

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