生殖腺调控衰老的机理研究

繁殖与衰老有着密切的联系，失去繁殖能力能够延长许多动物的寿命。线虫、果蝇等模式动物中的研究表明失去生殖细胞会激活生殖腺外多个组织中的信号通路、延缓动物的衰老。这些信号通路也被统称为生殖腺长寿信号。然而，生殖腺长寿信号的源头却仍依旧不明。人们依旧不知道当失去生殖细胞时，生殖腺内究竟产生了什么变化，而这些变化又是如何调控了其它组织的衰老进程。这也使得迄今没有高效的基于生殖腺长寿信号的干预衰老方法。申请人在前期研究中发现线虫生殖干细胞的微环境DTC细胞可能是生殖腺长寿信号的源头。在生殖细胞缺失时，DTC细胞的转录组发生了巨大的变化。在DTC细胞特异性地干扰其中一些基因的表达变化可以有效地调控线虫的衰老。本项目计划深入研究DTC细胞感知生殖细胞缺失和调控其它组织衰老的机理，在阐明解析生殖腺长寿信号源头的分子机制的基础上进一步解析繁殖与衰老之间的相互作用机制。

Reproduction and ageing are tightly linked. Loss of reproduction extends the lifespan of various animal species. Previous studies in worms and flies indicate that the loss of germ cells results in the activation of multiple signalling pathways outside the germline and in turn promotes longevity. These signalling pathways are therefore called germline longevity signalling. However, the origin of the germline longevity signalling remains a mystery. What changes occur in the germline upon the depletion of germ cells and how these changes control the ageing in other tissues are still unknown. Due to the lack of these knowledges, no efficient ageing intervention on wild type animals has been discovered from germline longevity signalling. The preliminary studies of this project in C. elegans suggest that the distal tip cell (DTC), which is the niche of germline stem cells, could be the source of the germline longevity signalling. Upon the depletion of germ cells, its transcriptome undergoes remarkable changes. Specific inhibition of genes expression changes in DTC effectively modulates the ageing of worms. The aim of this project is to explore how DTC senses the presence of germ cells and how it regulates the ageing in other tissues. By elucidating the molecular mechanism underlying the beginning of the germline longevity signalling, this project is to further decipher the interaction between reproduction and ageing.