Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition
Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition
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DOI：
10.18632/aging.102944
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发表时间：
2020-03-31
期刊：
影响因子：
5.2
通讯作者：
Merry, Troy L.
中科院分区：
文献类型：
--
作者：
D'Souza, Randall F.;Woodhead, Jonathan S. T.;Merry, Troy L.
线粒体衰老过程的调节部分是通过线粒体基因组编码的12 S rRNA-c（MOTS-c）的线粒体开放阅读框小调节肽来实现的。在这里，我们研究了MOTS-c在健康老年男性的血浆和骨骼肌中的调节。循环MOTS-c随着年龄的增长而减少，但老年人（70-81岁）和中年人（45-55岁）的骨骼肌MOTS-c表达比年轻人（18-30岁）高1.5倍。血浆MOTS-c水平仅与年轻男性的血浆相关，与慢型肌肉的标志物相关，并与老年组的肌肉质量改善相关（相对于大腿横截面积的最大腿部按压负荷）。使用小的mRNA检测，我们提供的证据表明，MOTS-C转录可能独立于全长12 S rRNA基因，它是编码的，表达是不相关的抗氧化反应元件（ARE）相关基因，如以前在文化。我们的研究结果表明，血浆和肌肉MOTS-c的差异调节与年龄，肌肉MOTS-c表达随年龄的增加是一致的快到慢型肌纤维的转变。需要进一步的研究来确定人类肌肉中内源性MOTS-c的分子靶点，但它们可能与维持肌肉质量的因素有关。
Mitochondria putatively regulate the aging process, in part, through the small regulatory peptide, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) that is encoded by the mitochondrial genome. Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men. Circulating MOTS-c reduced with age, but older (70-81 y) and middle-aged (45-55 y) men had similar to 1.5-fold higher skeletal muscle MOTS-c expression than young (18-30 y). Plasma MOTS-c levels only correlated with plasma in young men, was associated with markers of slow-type muscle, and associated with improved muscle quality in the older group (maximal leg-press load relative to thigh cross-sectional area). Using small mRNA assays we provide evidence that MOTS-c transcription may be regulated independently of the full length 12S rRNA gene in which it is encoded, and expression is not associated with antioxidant response element (ARE)-related genes as previously seen in culture. Our results suggest that plasma and muscle MOTS-c are differentially regulated with aging, and the increase in muscle MOTS-c expression with age is consistent with fast-to-slow type muscle fiber transition. Further research is required to determine the molecular targets of endogenous MOTS-c in human muscle but they may relate to factors that maintain muscle quality.