人口老龄化问题席卷全球。延缓衰老、防治衰老相关疾病和实现健康老龄化，已成为生物医学的前沿领域。延缓干细胞衰老对衰老及其相关疾病的防治有重要意义。项目组自补益菌类药灵芝中挖掘到三萜类化合物ganoderic acid D (GA-D)，具有显著的延缓人源性干细胞衰老的功效。基于前期研究与文献报道，我们推测“GA-D延缓干细胞衰老是以p53/p21信号与激活端粒酶为主导的多靶点、多途径分子信号调控的结果”。本项目拟采用分子生物学、免疫印迹、RNA干扰等技术，揭示GA-D延缓干细胞衰老的分子信号途径及其关键因子的响应规律，并运用基因组学、磷酸化蛋白组学、MALDI-TOF MS/MS、INVDOCK分析等技术，发现可能的新靶点新机制，进而评价其对衰老动物模型及其骨髓间充质干细胞的影响。这将为延缓干细胞衰老及研发抗衰老新制剂提供科学依据，为延缓衰老及衰老相关疾病的治疗提供新思路。

The aging population poses a serious challenge to families and the society in the world. Currently, therefore, the anti-aging, prevention and treatment of aging-related diseases and achieving the healthy aging are the frontier in the biomedical field. Here the study of delaying the stem cell aging is of great significance for the prevention of aging and aging-related diseases. Our group found that natural triterpenoid ganoderic acid D (GA-D) from famous Chinese medicinal mushroom Ganoderma lucidum showed potent activity against aging of human amniotic mesenchymal stem cells (hAMSCs). Based on our preliminary results and related research progress, we presume that the aging mechanism of GA-D involves a complex signaling network with multi-target and multi-pathway that p53/p21 signaling and activation of telomerase play an important role. To verify the hypothesis, accordingly, a series of experimental techniques such as RT-PCR, immunoblotting, and RNAi will be employed to investigate the anti-aging signaling pathway of GA-D in hAMSCs and the corresponding changes properties of key factors for the first time. Furthermore, a combined analysis involving the functional genomics, phosphoproteomics, MALDI-TOF MS/MS, two dimensional gel electrophoresis and INVDOCK analysis will be applied to discover possible new anti-aging mechanism of GA-D. Meanwhile, we will further evaluate the effect of GA-D on aging mice model and its bone marrow mesenchymal stem cells and their possible mechanism. This work will replenish and enrich the moleclular regulatory networks of delaying stem cells aging, provide new intervention strategy for stem cell aging, and promote the development of new anti-aging agent. Also, it is helpful for the development of anti-aging, prevention and treatment of aging-related diseases and achieving the healthy aging.