Werner 并发症是由WRN 基因突变引起的最典型的未老先衰的遗传疾病.WRN蛋白质在DNA修复，复制，以及重组中发挥着重要的作用。SIRT1是一种依赖于烟酰胺腺嘌呤二核苷酸(NAD+)的组蛋白脱乙酰酶。SIRT1定位于细胞核内, 除组蛋白外, 还有许多转录因子作为底物。众多的不同功能的底物的调节表明SIRT1是一个多功能的蛋白。它与众多肿瘤细胞以及人体细胞衰老过程相关，并参与了代谢过程，循环系统以及神经系统的维护调节.我们在前期的预实验中发现:WRN蛋白是SIRT1的调节底物。作为都与衰老相关的两个蛋白的结合，明显提示我们这两个蛋白极有可能互相作用共同调节人体及细胞的衰老。在本课题的研究中，我们将检验这两个蛋白在细胞中的直接联系，探索SIRT1调节WRN的功能及其在细胞衰老过程中的作用。

Werner syndrome is an autosomal recessive disorder associated with pre-mature aging and cancer predisposition caused by mutations of the WRN gene. WRN is a member of the RecQ DNA helicase family with functions in DNA replication, recombination and DNA repair. SIRT1 is an NAD-dependent histone deacetylase and has been found regulating premature cellular senescence induced by the tumor suppressors PML and p53. Recent study also indicates that SIRT1 plays an important role in calorie restriction promoted mammalian cell survival.Our preliminary data have shown that WRN can be acetylated in vivo in response to DNA damage and the acetylation can alter both the helicase and exonuclease activities of WRN protein; WRN can interact with SIRT1 both in vitro and in vivo; and SIRT1 can deacetylate WRN in the cells. The overall objective of this project is to address the regulation of the WRN protein by acetylation and deacetylation, and to understand the role of SIRT1 in this process.