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Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay

机译:肌生长抑制素作为肌肉减少症与肌肉质量稳态调节剂的介体:使用基于质谱的新检测方法的见解

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Background Myostatin is a protein synthesized and secreted by skeletal muscle that negatively regulates muscle mass. The extent to which circulating myostatin levels change in the context of aging is controversial, largely due to methodological barriers. Methods We developed a specific and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay to measure concentrations of myostatin and two of its key inhibitors, follistatin-related gene (FLRG) protein and growth and serum protein-1 (GASP-1) in 80 younger (65 years), and 80 sarcopenic older women and men. Results Older women had 34 % higher circulating concentrations of myostatin than younger women. Per unit of lean mass, both older and sarcopenic older women had?>23 % higher myostatin levels than younger women. By contrast, younger men had higher myostatin concentrations than older men with and without sarcopenia. Younger men had approximately twofold higher concentrations of myostatin than younger women; however, older women and sarcopenic older women had significantly higher relative myostatin levels than the corresponding groups of men. In both sexes, sarcopenic older subjects had the highest concentrations of FLRG. Circulating concentrations of myostatin exhibited positive, but not robust, correlations with relative muscle mass in both sexes. Conclusions Our data suggest that myostatin may contribute to the higher prevalence of sarcopenia in women but acts as a homeostatic regulator of muscle mass in men. Moreover, this new LC-MS/MS-based approach offers a means to determine the extent to which myostatin serves as a biomarker of muscle health in diverse conditions of muscle loss and deterioration.
机译:背景Myostatin是由骨骼肌合成和分泌的一种蛋白质,对肌肉质量有负调节作用。在衰老过程中循环肌生长抑制素水平变化的程度是有争议的,这在很大程度上是由于方法上的障碍。方法我们开发了一种特异性灵敏的液相色谱-串联质谱(LC-MS / MS)测定法来测定肌生长抑制素及其两种主要抑制剂,卵泡抑素相关基因(FLRG)蛋白以及生长和血清蛋白1(GASP)的浓度-1)在80位年轻(65岁)和80位少肌症的老年男女中。结果老年妇女的肌生长抑制素循环浓度比年轻妇女高34%。每单位瘦体重,老年和少肌症的老年妇女的肌抑制素水平都比年轻女性高> 23%。相比之下,年轻男子的肌肉抑制素浓度要高于有或没有肌肉减少症的老年男子。年轻男性的肌生长抑制素浓度大约是年轻女性的两倍。但是,老年妇女和少肌症老年妇女的肌肉生长抑制素相对水平明显高于相应的男性。在男性和女性的少肌症患者中,FLRG的浓度最高。循环中的肌生长抑制素浓度与男性相对肌肉质量呈正相关关系,但不强健。结论我们的数据表明,肌生长抑制素可能有助于女性少肌症的流行,但可以作为男性肌肉质量的稳态调节剂。而且,这种新的基于LC-MS / MS的方法提供了一种手段,可以确定在各种肌肉丢失和恶化的情况下,肌肉生长抑制素在多大程度上成为肌肉健康的生物标志物。

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