自噬在迟发性性腺机能减退发生过程中功能和作用机制的研究

本项目面向我国老龄化人口的不断增加以及老龄化人口生殖健康提高的重要需求，研究自噬在迟发型性腺功能减退症中的致病机理，并探讨其作为相关疾病临床治疗新型靶点的可能性。自噬是真核细胞中最重要的两种降解途径之一，参与了多种器官的发育和组织分化，是重大细胞改造过程中实现物质循环再利用的主要途径。男性迟发性性腺功能减退症是一种与男性年龄增长及衰老相关的获得性性腺功能减退综合征，特征为血清睾酮水平降低并伴有一系列临床症状，严重影响男性生活质量。前期研究结果表明睾丸间质细胞自噬缺陷引起小鼠呈现迟发性性腺功能减退症，但仍需要进一步研究明确自噬缺陷诱发老年小鼠迟发性性腺功能减退症症状的调控机制，本研究主要基于组织及时空特异性小鼠基因敲除体系，深入揭示自噬在迟发型性腺功能减退症的致病机制，探索以自噬为靶点的防治策略，从而为器官衰老及其相关疾病的研究开拓新视角。

The radical increase in aging population and concomitant deteriorative reproductive health of the elder are important issues for our modern society, and the aim of this project is to investigate the role of autophagy in the aging related androgen deficiency diseases such as late-onset hypogonadism (LOH), and explore the possibility to target autophagy for potential treatment. Autophagy is one of the two major degradation pathways in the eukaryotes, which mainly recycles the cellular material to provide energy for the cells under stress condition and participates in a number of development and cellular differentiation processes. The LOH is an aging-related hypogonadism with clinical manifestation of decreased serum testosterone level. Our preliminary result showed that steroidogenic cell specific disruption of autophagy induced LOH symptom in aging male mice, however the exact underlying mechanism is not well understood. We will utilize conditional knockout mice models to study the mechanism of autophagy in the hypogonadism and explore the possibilities of targeting autophagy as preventive or therapeutical strategies. The results of this study might open a new area for organ senescence and senescence-related disease diagnosis, and improve the health of the elder man.