细胞复制性衰老过程中mTORC1靶基因的筛选与功能研究

项目名称： 细胞复制性衰老过程中mTORC1靶基因的筛选与功能研究

项目编号： No.31501108

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 刘峰

作者单位： 中山大学

项目金额： 21万元

中文摘要： 细胞复制性衰老是个体衰老的基础，与衰老相关疾病，如神经退行性疾病和肿瘤等的发生和发展紧密相连。在细胞复制性衰老的过程中，许多基因的表达水平会发生改变，而这些细胞衰老相关基因的表达产物也会影响细胞衰老进程；但目前对此过程的系统性研究较少，尤其是在基因表达调控的mRNA翻译层次更是未见报道。本项目拟以mTORC1在细胞复制性衰老过程中发挥重要功能为突破口，采用多聚核糖体纯化技术和RNA高通量测序技术来筛选在细胞复制性衰老过程中其翻译水平受到mTORC1调控的mRNA种类，寻找复制性衰老相关基因。进一步利用慢病毒介导的RNA干涉技术和CRISPR/Cas9敲除小鼠技术分别在细胞层次和个体层次研究筛选出的基因在衰老过程中的作用。本项目研究结果将加深我们对于衰老过程和衰老相关疾病的认识；本项目筛选出的衰老相关基因，有利于我们寻找治疗衰老相关疾病的靶点，为研发新的治疗方法提供重要参考和依据。

中文关键词： 细胞老化；老化；衰老蛋白；端粒；端粒长度

英文摘要： Cell replicative senescence is fundamental to organismal aging, which correlates to aging-related diseases, such as neurodegenerative disease and cancer. During replicative senescence, many genes alter their expression levels, and their gene products also contribute to the initiation or development of cell senescence. However, few studies focus on the screening research on that process; and which mRNA’s translation is regulated by replicative senescence is largely unknown. This study is based on that mTORC1 plays an essential role in replicative senescence. By using polysomal profiling and RNA-seq, we try to screen novel senescence-associated genes whose translation is regulated by mTORC1 during cell replicative senescence. Furthermore, we attempt to analyze those genes’ function on both cellular level and organismal level by utilizing lentivirus-mediated RNA knockdown in cells and CRISPR/Cas9-mediated gene knockout in mice, separately. This study will enable us to have a deeper understanding of aging process and aging-related disease. Screening of novel senescence-associated genes will help to find new targets for the treatment of aging-related diseases and provide important guidance for therapies.

英文关键词： cell senescence;senescence;senescence-related protein;telomere;telomere length