LncRNA AK077294/miR-217-5p通过Grb10参与老年肌肉减少症的机制研究

肌肉减少症(肌少症)是一种以骨骼肌质量减少、肌力下降和机体功能减退为特征的骨骼肌疾病，严重影响了老年人的身体健康。遗传因素、肌卫星细胞功能异常与肌少症发病有关。肌卫星细胞功能衰减引起肌肉再生能力下降，是肌少症的发病机制之一。衰老的骨骼肌虽然存在大量差异性表达的lncRNA，但其中大部分lncRNA的功能尚不明确。我们前期研究发现lncRNA AK077294 (lncRNA 077)在老年小鼠腓肠肌中表达显著，与肌卫星细胞增殖分化能力下降呈负相关性。Grb10是胰岛素样生长因子-1信号通路的负向调节分子，与肌再生有关。结合前期实验及生物信息学预测分析，我们推测lncRNA 077可能调控Grb10，从而抑制卫星细胞增殖分化。因此本项目拟以老年小鼠及D-半乳糖诱导的肌卫星细胞为对象，探究lncRNA 077是否通过调节Grb10影响肌再生过程，进一步丰富肌少症的发病机制。

Sarcopenia is an age-related skeletal muscle disease characterized by a decline in skeletal muscle mass and muscle strength and that severely affects the health of the elderly. Genetics and myosatellite cell function are related to the pathogenesis of sarcopenia. Decreased proliferation and differentiation of muscle satellite cells is the key cause in the decline of skeletal muscle regeneration in the elderly, which is involved in the pathogenesis of sarcopenia. Studies have reported that there are a large number of differentially expressed lncRNAs in elderly skeletal muscle, but most of them have not been reported. Recently we found that lncRNA AK077294 (lncRNA 077) was significantly expressed in the gastrocnemius muscle of aging mice, which was strongly correlated with the decrease of proliferation and differentiation of myosatellite cells. Grb10 has been known as a negative regulator of insulin-like growth factor signaling pathway, which is related with muscle regeneration. Combined with previous experiments and bioinformatics prediction analysis, we speculated that lncRNA 077 might inhibit the proliferation and differentiation of satellite cells by targeting Grb10.Therefore, this project aims to explore whether lncRNA 077 affects muscle regeneration by targeting Grb10 in aging mice and D-galactose-induced senescent satellite cell, so as to provide a theoretical basis for the clinical search for sarcopenia intervention targets.