Piec Isabelle, Listrat Anne, Alliot Josette, Chambon Christophe, Taylor Richard G, Bechet Daniel
Human Nutrition Research Center, Nutrition and Protein Metabolism Laboratory, INRA UR551, Ceyrat, France.
FASEB J. 2005 Jul;19(9):1143-5. doi: 10.1096/fj.04-3084fje. Epub 2005 Apr 14.
To identify the mechanisms underlying muscle aging, we have undertaken a high-resolution differential proteomic analysis of gastrocnemius muscle in young adults, mature adults, and old LOU/c/jall rats. Two-dimensional gel electrophoresis and subsequent MALDI-ToF mass spectrometry analyses led to the identification of 40 differentially expressed proteins. Strikingly, most differences characterized old (30-month) animals, whereas young (7-month) and mature (18-month) adults exhibited similar patterns of expression. Important modifications in contractile (actin, myosin light-chains, troponins-T) and cytoskeletal (desmin, tubulin) proteins, and in essential regulatory proteins (gelsolin, myosin binding proteins, CapZ-beta, P23), likely account for dysfunctions in old muscle force generation and speed of contraction. Other features support decreases in cytosolic (triose-phosphate isomerase, enolase, glycerol-3-P dehydrogenase, creatine kinase) and mitochondrial (isocitrate dehydrogenase, cytochrome-c oxidase) energy metabolisms. Muscle aging is often associated with increased oxidative stress. Accordingly, we observed differential regulation of molecular chaperones (hsp20, hsp27, reticuloplasmin ER60) and of proteins implicated in reactive aldehyde detoxification (aldehyde dehydrogenase, glutathione transferase, glyoxalase). We further noticed up-regulation of proteins involved in transcriptional elongation (RNA capping protein) and RNA-editing (Apobec2). Most of these proteins were previously unrecognized as differentially expressed in old muscles, and they represent novel starting points for elucidating the mechanisms of muscle aging.
为了确定肌肉衰老的潜在机制，我们对年轻成年大鼠、成年大鼠和老年LOU/c/jall大鼠的腓肠肌进行了高分辨率差异蛋白质组学分析。二维凝胶电泳和随后的基质辅助激光解吸电离飞行时间质谱分析鉴定出40种差异表达蛋白。引人注目的是，大多数差异表现在老年（30个月）动物身上，而年轻（7个月）和成年（18个月）大鼠表现出相似的表达模式。收缩蛋白（肌动蛋白、肌球蛋白轻链、肌钙蛋白-T）和细胞骨架蛋白（结蛋白、微管蛋白）以及重要调节蛋白（凝溶胶蛋白、肌球蛋白结合蛋白、CapZ-β、P23）的重要修饰，可能是老年肌肉力量产生和收缩速度功能障碍的原因。其他特征表明细胞溶质（磷酸丙糖异构酶、烯醇化酶、甘油-3-磷酸脱氢酶、肌酸激酶）和线粒体（异柠檬酸脱氢酶、细胞色素c氧化酶）能量代谢降低。肌肉衰老通常与氧化应激增加有关。因此，我们观察到分子伴侣（热休克蛋白20、热休克蛋白27、网织质浆蛋白ER60）以及参与活性醛解毒的蛋白（醛脱氢酶、谷胱甘肽转移酶、乙二醛酶）的差异调节。我们还注意到参与转录延伸（RNA封端蛋白）和RNA编辑（载脂蛋白B mRNA编辑酶催化多肽2）的蛋白上调。这些蛋白中的大多数以前未被认为在老年肌肉中差异表达，它们代表了阐明肌肉衰老机制的新起点。
