Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Proteomics. 2014 Jan;14(1):121-32. doi: 10.1002/pmic.201200497.
Aging is associated with a progressive loss of skeletal muscular function that often leads to progressive disability and loss of independence. Although muscle aging is well documented, the molecular mechanisms of this condition still remain unclear. To gain greater insight into the changes associated with aging of skeletal muscle, we performed quantitative proteomic analyses on young (6 months) and aged (27 months) mouse gastrocnemius muscles using mTRAQ stable isotope mass tags. We identified and quantified a total of 4585 peptides corresponding to 236 proteins (protein probability >0.9). Among them, 33 proteins were more than 1.5-fold upregulated and 20 proteins were more than 1.5-fold downregulated in aged muscle compared with young muscle. An ontological analysis revealed that differentially expressed proteins belonged to distinct functional groups, including ion homeostasis, energy metabolism, protein turnover, and Ca(2+) signaling. Identified proteins included aralar1, β-enolase, fatty acid-binding protein 3, 3-hydroxyacyl-CoA dehydrogenase (Hadh), F-box protein 22, F-box, and leucine-rich repeat protein 18, voltage-dependent L-type calcium channel subunit beta-1, ryanodine receptor (RyR), and calsequestrin. Ectopic expression of calsequestrin in C2C12 myoblast resulted in decreased activity of nuclear factor of activated T-cells and increased levels of atrogin-1 and MuRF1 E3 ligase, suggesting that these differentially expressed proteins are involved in muscle aging.
衰老是与骨骼肌功能逐渐丧失相关的，这通常会导致进行性残疾和丧失独立性。尽管肌肉衰老已有充分的记载，但这种情况的分子机制仍不清楚。为了更深入地了解与骨骼肌衰老相关的变化，我们使用 mTRAQ 稳定同位素质量标签对年轻（6 个月）和年老（27 个月）小鼠腓肠肌进行了定量蛋白质组学分析。我们总共鉴定和定量了 4585 个对应于 236 种蛋白质的肽段（蛋白质概率>0.9）。其中，与年轻肌肉相比，年老肌肉中有 33 种蛋白质的上调倍数超过 1.5 倍，20 种蛋白质的下调倍数超过 1.5 倍。一个本体论分析表明，差异表达的蛋白质属于不同的功能组，包括离子稳态、能量代谢、蛋白质周转和 Ca(2+)信号。鉴定出的蛋白质包括 aralar1、β-烯醇酶、脂肪酸结合蛋白 3、3-羟基酰基辅酶 A 脱氢酶（Hadh）、F-box 蛋白 22、F-box 和富含亮氨酸重复蛋白 18、电压依赖性 L 型钙通道亚基 β-1、Ryanodine 受体（RyR）和钙网蛋白。钙网蛋白在 C2C12 成肌细胞中的异位表达导致核因子活化 T 细胞的活性降低，并且 atrogin-1 和 MuRF1 E3 连接酶的水平增加，这表明这些差异表达的蛋白质参与了肌肉衰老。
