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首页> 外文期刊>Cellular Physiology and Biochemistry >Mechanistic Links Underlying the Impact of C-Reactive Protein on Muscle Mass in Elderly
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Mechanistic Links Underlying the Impact of C-Reactive Protein on Muscle Mass in Elderly

机译：C反应蛋白对老年人肌肉质量影响的潜在机制链接

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>Background/Aims: Mechanisms underlying the relationship between systemic inflammation and age-related decline in muscle mass are poorly defined. The purpose of this work was to investigate the relationship between the systemic inflammatory marker CRP and muscle mass in elderly and to identify mechanisms by which CRP mediates its effects on skeletal muscle, in-vitro. Methods: Muscle mass and serum CRP level were determined in a cohort of 118 older women (67?±1.7 years). Human muscle cells were differentiated into myotubes and were exposed to CRP. The size of myotubes was determined after immunofluorescent staining using troponin. Muscle protein synthesis was assessed using stable isotope tracers and key signalling pathways controlling protein synthesis were determined using western-blotting. Results: We observed an inverse relationship between circulating CRP level and muscle mass (?2= -0.646 (95% CI: -0.888, -0.405) p<0.05) and demonstrated a reduction (p < 0.05) in the size of human myotubes exposed to CRP for 72 h. We next showed that this morphological change was accompanied by a CRP-mediated reduction (p < 0.05) in muscle protein fractional synthetic rate of human myotubes exposed to CRP for 24 h. We also identified a CRP-mediated increased phosphorylation (p<0.05) of regulators of cellular energy stress including AMPK and downstream targets, raptor and ACC-?2, together with decreased phosphorylation of Akt and rpS6, which are important factors controlling protein synthesis. Conclusion: This work established for the first time mechanistic links by which chronic elevation of CRP can contribute to age-related decline in muscle function.
机译：> 背景/目标 ：系统性炎症与年龄相关的肌肉质量下降之间的关系机制尚不明确。这项工作的目的是研究老年人体内全身炎症标记物CRP与肌肉质量之间的关系，并确定CRP介导其对骨骼肌影响的机制。 方法： 在118名年龄较大的女性（67？±1.7岁）队列中测定了肌肉质量和血清CRP水平。人肌肉细胞分化为肌管，并暴露于CRP。使用肌钙蛋白进行免疫荧光染色后确定肌管的大小。使用稳定的同位素示踪剂评估肌肉蛋白质的合成，并使用蛋白质印迹法确定控制蛋白质合成的关键信号通路。 结果： 我们观察到循环CRP水平与肌肉质量呈负相关（？2 = -0.646（95％CI：-0.888，-0.405），p <0.05），并且证实暴露于CRP 72小时的人类肌管尺寸减少（p <0.05）。接下来，我们表明，这种形态学改变伴随着CRP介导的24小时暴露于CRP的人肌管的肌肉蛋白质分数合成速率的降低（p <0.05）。我们还确定了CRP介导的细胞能量应激调节剂（包括AMPK和下游靶标，猛禽和ACC-α2）的磷酸化增加（p <0.05），以及Akt和rpS6的磷酸化减少，这是控制蛋白质合成的重要因素。 结论： 这项工作首次建立了机械联系，据此，慢性CRP升高可导致与年龄相关的肌肉功能下降。

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