核转录因子FoxG1在听觉系统退行性变中的作用机制及干预措施

老年性聋是指随着年龄增长，双耳听力进行性下降的感音神经性耳聋。老年性聋的病因尚不清楚，其发病机制至今尚未完全阐明，近年来研究发现线粒体DNA的缺失和突变与老年性聋有着密切关系,而核转录因子在线粒体的功能调控中具有重要作用。有研究报导FoxG1在线粒体能量代谢及合成中具有重要的调控作用，但是在听觉退行性变的研究中关于核因子却鲜有报道。在前期研究中，我们发现自噬及FoxG1表达水平在动物及细胞衰老模型中均出现下降，提示在听觉退行性变过程中FoxG1可能通过与自噬或相关信号通路的协同调控从而发挥重要作用。本项目将从听觉中枢系统及外周器官的退行性变着手，重点研究FoxG1在耳蜗毛细胞衰老进程中的调控机制，希望通过FoxG1与代谢及凋亡相关信号的协同调控达到维持毛细胞的存活及功能的目的，从而部分延缓听力减退，为以后在临床上应用基因方法治疗老年性聋奠定理论和实验基础。

Presbycusis is the cumulative effect of aging on hearing. It is a progressive.bilateral symmetrical sensorineural hearing loss. So far the causes of the.deafness is unknown, the mechanisms involved in the degeneration of auditory has.not yet been fully elucidated. Recent studies have shown that the mitochondrial.common deletion is closely related to deafness caused by degenerative changes in.the auditory system and some nuclear factors are proposed to participate in the regulation of mitochondrial function. FoxG1 plays an important role in the regulation of mitochondrial energy metabolism and synthesis, but it is not been reported in the study of auditory degeneration. In this study, we investigate the regulation mechanism of FoxG1 in auditory central system and peripheral organs in the aging process. We also explore whether the survival and function of the hair cell can be maintained by the coordinated regulation of FoxG1 with metabolism or apoptosis related signal pathway. This study supplied foundation to investigate the pathogenesis of hearing loss caused by degeneration of auditory system and measures of prevention and cure.