衰老相关长链非编码RNA的鉴定及其功能研究

LncRNA可在多种层面上（表观遗传调控、转录调控以及转录后调控等）调控基因的表达，并参与细胞增殖和分化等生物学过程。然而lncRNA在细胞衰老中的作用尚待挖掘。本项目的前期研究结果表明，在细胞衰老过程中lncRNA表达谱具有明显的差异，提示这些差异表达lncRNA可能与细胞衰老密切相关。本项目拟在已有工作基础上全面系统鉴定衰老相关lncRNA；通过研究衰老相关lncRNA在不同年龄段的人和小鼠组织中的差异表达，探讨它们与生理性衰老的关系；通过在年轻或衰老MEF细胞中改变衰老相关lncRNA的表达，观察它们是否可促进或延缓细胞衰老；利用RNA-pull down、蛋白质谱和RNA免疫共沉淀等技术筛查与lncRNA特异性结合的蛋白质，再深入探讨这些lncRNA协同结合蛋白影响细胞衰老的分子机制。本研究对于理解lncRNA参与细胞衰老的分子机制，深化认识衰老和衰老相关疾病的机制具有重要的意义。

Long non-coding RNAs (lncRNAs) play vital roles in gene expression regulation at the level of epigenetic regulation and transcriptional and posttranscriptional modification, and are key regulators of diverse biological processes such as cell growth and differentiation. However, the biological significance of lncRNAs on cellular senescence is still unknown. Based on our previous data, the expression of lncRNAs show obvious difference between young and senescent MEFs, suggesting that these differentially expressed lncRNAs may be closely associated with cellular senescence. Therefore, the aim of this study is to validate these differentially expressed lncRNAs in young and senescent MEFs by real-time qRT-PCR, and to study the relationship of these lncRNAs with physiological aging through analyzing the expression of lncRNAs in the tissues of mice and humans with different age, and then to explore their roles on cellular senescence through inhibition of the lncRNA expression in young or senescent MEFs, and to identify specific binding proteins of lncRNAs using RNA-pull down and RNA-binding protein immunoprecipitation, and then explore the underlying mechanism of these lncRNAs on cellular senescence. This study will contribute to understand the biological significance of lncRNAs on cellular senescence, and is of great importance for understanding the mechanism of aging and aging-related diseases.