运动诱导miRNAs经SIRT1介导调控衰老骨骼肌蛋白代谢的机理研究

The imbalance of protein metabolism had important influence on the process of aging muscle atrophy, and the ability of older's response and adaptation to exercise was significantly impaired. Some researchs reported miRNAs play important role on muscle growth, differentiation and myogenesis, and activiting SIRT1 contributed to cell survival and longevity. The research of regulation on miRNAs, SIRT1 and exercise on skeletal muscle atrophy during aging were still unclear. Set up the mice model of aging and resistance exercise, and use techniques of gene chips, plasmid transfection and RNA interference to screening the special miRNAs, and make these special miRNAs overexpression or repression, and activate or inhibite SIRT1, to elucidate the mechanisms of miRNAs and SIRT1 on protein metabolism of aging skeletal muscle, and exercise induced miRNAs regulating protein metabolism in aging skeletal muscle mediated by SIRT1. We hoped this study would had progress on regulating mechanism of atrophy by aging, laid the theoretical foundation for the muscle anti-aging on skeletal muscle, and reduced or delayed the incidence of atrophy by aging.

蛋白代谢失衡在衰老性肌萎缩过程中有重要影响，同时衰老骨骼肌对运动的反应与适应能力也明显受损。研究认为，miRNAs对肌肉的生长、分化、增殖起着重要作用。SIRT1利于细胞存活，且具有延寿效应。目前对衰老性肌萎缩过程中，miRNAs、SIRT1和运动的对其蛋白代谢的作用机理缺乏深入研究。本研究建立动物抗阻运动模型，采用基因芯片、细胞转染、RNA干扰等技术手段，筛选出衰老骨骼肌在运动性肥大过程中的特异miRNAs，并对这些特异miRNAs的表达进行干预，同时结合对SIRT1信号激活与抑制，从而阐明miRNAs与SIRT1在调节衰老骨骼肌蛋白代谢中的作用，以及运动干预后诱导miRNAs，并经SIRT1介导调控衰老骨骼肌蛋白代谢的分子机制。以期通过本项目的研究进一步揭示衰老性肌萎缩的蛋白代谢调控机理，为运动抗衰老性肌萎缩奠定理论基础，从而减少或推迟衰老性肌萎缩的发生。