肝细胞的衰老机制及衰老逆转的研究

项目名称： 肝细胞的衰老机制及衰老逆转的研究

项目编号： No.31271474

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 何志颖

作者单位： 中国人民解放军第二军医大学

项目金额： 80万元

中文摘要： 人口老龄化带来的器官衰老与人类的健康密切相关，其中肝脏衰老的机理是最亟待解决的问题之一。关于损伤后肝脏重建和肝细胞移植的研究表明，在成体动物中肝脏的连续再生实现了肝细胞的连续增殖，这种情况下的肝细胞打破了细胞衰老的规则，表现为无限增殖的能力。但由于缺乏理想的动物模型，既不能实现特定肝细胞在体内的长期连续增殖，也无法对体内连续增殖的肝细胞进行分离纯化或追踪分析，成为制约肝细胞衰老机制研究的瓶颈问题。本申请旨在利用FAH基因剔除小鼠能够连续移植肝细胞的特性，使得肝细胞的连续增殖及其分离、分选和追踪分析成为可能。运用细胞遗传学和分子生物学研究手段，分析连续增殖中肝细胞衰老的表型特征，探讨倍体转换在肝细胞衰老或衰老逆转中的作用，分析连续增殖中肝细胞衰老抑制或逆转的分子机制。由此获得肝脏衰老的发生发展规律，理解延缓或逆转肝脏衰老的机制，制定延缓或逆转肝脏衰老的参考方案，具有重要的生物学和医学意义。

中文关键词： 肝细胞；多倍体；细胞衰老；衰老逆转；倍体转换

英文摘要： Population aging and health problems caused by the aging organs have become the major scientific issues of population in the field of health sciences. Understanding of both development and the mechanism for liver aging has the special significance, which could be used to delay or reverse liver senescence. Liver cells in vivo are special in that they are the highly differentiated cells with strong capacity of cell proliferation. Mature hepatocytes keep quiescent, but are immediately entering into cell cycle under the stimulation of injury. Until now, the limit of proliferation capacity for hapatocytes is still a long-term unsolved question. The proliferation characteristic of hepatocytes during liver regeneration has not been studied yet for without an in vivo model system capable of keeping hepatocytes in continuous proliferation. Taking advantaging of Fah-/- mouse model with hepatocyte serial transplantation, this application proposes to study the details of how proliferating hepatocytes avoid or inhibit their senescence during their process of continuous proliferation. The proposed researches will also include to study the role of chromosome ploidy conversion in the process of inhibiting hepatocyte senescence, and to find the special cell signaling pathways involved in the regulation of by-path or reversal of

英文关键词： Hepatocyte；Polyploid；Cell senescnece；Rejuvenation；Ploidy reversal