Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria
Discovery proteomics in aging human skeletal muscle finds change in spliceosome, immunity, proteostasis and mitochondria
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DOI：
10.7554/elife.49874
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发表时间：
2019-10-23
期刊：
影响因子：
7.7
通讯作者：
Ferrucci, Luigi
中科院分区：
文献类型：
--
作者：
Ubaida-Mohien, Ceereena;Lyashkov, Alexey;Ferrucci, Luigi
骨骼肌力量随年龄增长而下降是老年人活动能力丧失和虚弱的主要原因，但这种下降的分子机制尚不清楚。在这里，我们进行了定量蛋白质组学分析骨骼肌收集58名健康人，年龄在20至87岁。在老年人的肌肉中，核糖体蛋白和与能量代谢相关的蛋白质，包括与TCA循环、线粒体呼吸和糖酵解相关的蛋白质，代表性不足，而与先天性和适应性免疫、蛋白质稳态和选择性剪接有关的蛋白质代表性过高。与动物模型中的报告一致，老年人肌肉的特征是能量代谢紊乱，促炎环境和蛋白水解增加。通过RNA-seq分析证实了可变剪接随衰老的变化。我们认为，剪接机制的变化使肌肉细胞能够对衰老引起的损伤做出反应。
A decline of skeletal muscle strength with aging is a primary cause of mobility loss and frailty in older persons, but the molecular mechanisms of such decline are not understood. Here, we performed quantitative proteomic analysis from skeletal muscle collected from 58 healthy persons aged 20 to 87 years. In muscle from older persons, ribosomal proteins and proteins related to energetic metabolism, including those related to the TCA cycle, mitochondria respiration, and glycolysis, were underrepresented, while proteins implicated in innate and adaptive immunity, proteostasis, and alternative splicing were overrepresented. Consistent with reports in animal models, older human muscle was characterized by deranged energetic metabolism, a pro-inflammatory environment and increased proteolysis. Changes in alternative splicing with aging were confirmed by RNA-seq analysis. We propose that changes in the splicing machinery enables muscle cells to respond to a rise in damage with aging.