Molecular analyses provide insight into mechanisms underlying sarcopenia and myofibre denervation in old skeletal muscles of mice
Molecular analyses provide insight into mechanisms underlying sarcopenia and myofibre denervation in old skeletal muscles of mice
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DOI：
10.1016/j.biocel.2014.04.025
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Shavlakadze, Tea
中科院分区：
文献类型：
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作者：
Barns, Mitchell;Gondro, Cedric;Shavlakadze, Tea
在3、15、24、27和29个月(m)的雌性C57B1/6J小鼠中，描述了与年龄相关的神经支配丧失和骨骼肌质量和功能丧失（肌肉减少症）相关的分子机制。据报道，在从健康成人肌纤维到肌肉减少症（发生在15至24 m之间）的过渡过程中，衰老肌肉中与肌纤维失神经支配和蛋白质代谢相关的mrna和蛋白质的变化。24 m时肌肉减少症的发作与神经肌肉连接处去神经支配相关基因的表达增加相对应，这些基因包括Chnrg、Chrnd、Ncam1、Runx1、Gadd45a和Myog。股四头肌肌萎缩症也与Igf1受体、Akt和核糖体蛋白S6 （Rps6）蛋白水平升高相一致，Rps6 （Ser235/236）磷酸化增加，Murf1 mRNA和蛋白水平升高，但Fbxo32不升高：许多这些变化也与去神经支配有关。通过微阵列分析的全球转录谱证实了这些功能主题，并强调了可能与肌肉减少症相关的病理结果的其他主题，包括脂肪酸代谢、细胞外基质结构和蛋白质分解代谢的变化。衰老还与全球基因表达变异的增加有关，这与基因调控控制的减少相一致。(C) 2014 Elsevier Ltd.版权所有。
Molecular mechanisms that are associated with age-related denervation and loss of skeletal muscle mass and function (sarcopenia) are described for female C57B1/6J mice aged 3, 15, 24, 27 and 29 months (m). Changes in mRNAs and proteins associated with myofibre denervation and protein metabolism in ageing muscles are reported, across the transition from healthy adult myofibres to sarcopenia that occurs between 15 and 24 m. This onset of sarcopenia at 24 m, corresponded with increased expression of genes associated with neuromuscular junction denervation including Chnrg,Chrnd,Ncam1, Runx1, Gadd45a and Myog. Sarcopenia in quadriceps muscles also coincided with increased protein levels for Igf1 receptor, Akt and ribosomal protein S6 (Rps6) with increased phosphorylation of Rps6 (Ser235/236) and elevated Murf1 mRNA and protein, but not Fbxo32: many of these changes are also linked to denervation. Global transcription profiling via microarray analysis confirmed these functional themes and highlighted additional themes that may be a consequence of pathology associated with sarcopenia, including changes in fatty acid metabolism, extracellular matrix structure and protein catabolism. Ageing was also associated with increased global gene expression variance, consistent with decreased control of gene regulation. (C) 2014 Elsevier Ltd. All rights reserved.