果蝇pygo基因调控心脏衰老的分子机制研究

衰老是人类目前面临的全球性社会问题和健康挑战，心脏衰老是机体衰老的一个重要方面，了解心脏衰老的分子机制和遗传调控模式是预防和控制衰老的理论基础。果蝇模型寿命短、全基因组RNAi系齐全、基因Switch系统便于定点定时敲低基因表达且遗传互作研究方便，成为研究心脏衰老分子机制的理想模型。本项目在前期已经确定pygo基因与成体心脏衰老密切相关且调控衰老可能不通过经典的Wnt信号途径的基础上，进一步利用我们建立的心脏衰老研究技术平台详细研究pygo基因对心脏衰老的调控及其作用机制，并通过鉴定Wnt信号途径的关键成员TCF、arm、lgs以及离子通道基因CaMKII、Seizure 和Shaker等的心脏衰老表型以及它们与pygo基因相互作用和拯救表型，来确定pygo基因调控心脏衰老可能不通过Wnt信号途径而可能通过调控离子通道基因来调控心脏衰老的分子机制，为揭示心脏衰老的分子调控机制提供实验依据。

Aging is a global social issue and health challenges facing mankind, cardiac aging is an important aspect of aging. Understanding of the molecular mechanisms of cardiac aging is helpful for the prevention and control of aging. Owing to the short lifespan, complete genome-wide RNAi stocks and powerful Gene Switch system and convenient genetical interaction method, The Drosophila model has become the ideal model to study the molecular mechanisms of cardiac aging. Our previous study has suggested that gene pygo was related with adult cardiac aging independent with the classic Wnt signaling pathway. In this project, taking advantage of our established cardiac aging research platform, we would further study the regulation mechanisms of gene pygo in the aging heart. Also, we would like to identify the aging phenotypes and genetic interactions with pygo and rescue phenotypes to pygo knock-down flies of the key components of Wnt signaling pathway including TCF, arm, lgs and ion channel genes including CaMKII, Seizure and Shaker, to support the hypothesis of pygo regulating cardiac aging via affecting ion channel genes instead of Wnt signaling pathway.