细胞衰老是生物衰老的基本单位,老年病发病的共同基础。p16在细胞衰老、细胞周期调节，细胞永生化及肿瘤发生中都有重要作用。我们过去的工作证明，在p16启动子上游存在邻近的两个转录因子B-myb的结合元件，MBSI和MBSII, B-myb可与该元件直接结合，并发挥负调控作用；B-myb基因高表达可抑制细胞衰老进程。本项目拟在以往研究的基础上，通过染色质免疫共沉淀，电泳凝聚阻滞，位点突变，启动子报告基因表达等试验，深入研究B-myb与p16基因启动子结合和解离的机制，发挥负调控作用的机理，影响因素，与能量代谢、氧化应激和端粒等细胞衰老通路的联系等，寻找鉴定B-myb的其它靶基因，以及B-myb在细胞衰老过程中表达降低的原因。预期该调控机制的阐明，对于我们认识和干预细胞衰老进程，探索和治疗肿瘤等方面均有一定应用价值。

Cellular aging is the fundamental base of organic aging and senile diseases.p16 plays important roles in cellular aging, cell cycle regulation, cell immortalization and tumor genesis.Our previous data shows that two adjacent myb binding sites, MBSI和MBSII lie in p16 gene promoter, B-myb could bind to those elements and downregulate p16 gene expression, and B-myb could inhibited the process of cellular aging.Base on previous result and scientific hypothesis,this project is to explore the mechenism of the binding and dissociation of B-myb to p16 promoter,the model of the negetive regulation, influence factors and the relationship with energy metabolism, oxidative stress and telomere. We also want to search for other target genes regulated by B-myb and the reasons which cause the downregulated expression of B-myb.The result of this project will give us insight into the process and control of cellular aging, and even the therapy strategy of tumor.