NPTX2等位点甲基化与生物学年龄相关性及其在衰老中的作用机制

项目名称： NPTX2等位点甲基化与生物学年龄相关性及其在衰老中的作用机制

项目编号： No.81202385

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 幸宇

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： NPTX2，Edaradd,Tom1L1等基因的甲基化在小样本人群的基因扫描中被发现与年龄具有高度相关性，同时这些基因的甲基化状态又与神经系统和心血管系统等的疾病有明显的联系。本研究主要从分子生物学的方法入手，应用实时定量甲基化特异性PCR和其它细胞生物学及分子生物学的手段，一方面对重庆地区的汉族人群进行大样本量的针对前述基因的甲基化情况的调查，继而对最适用的样本来源组织进行筛选，通过数学和统计学方法来建立基于这些指标的年龄推断公式，并验证其适用性，以期为法医年龄推断提供新方法和策略；另一方面，构建对目的基因过表达和低表达的细胞模型，通过观察细胞形态，细胞的周期、凋亡检测，细胞增殖，并检测目的基因和衰老相关核心蛋白的表达情况，以期明确目的基因在衰老过程中的作用和机制，并为医学上提供基于生物学年龄的个性化疾病风险评估、预防和治疗的依据。

中文关键词： 生物学年龄；衰老；DNA甲基化；年龄推断；表观遗传学

英文摘要： The methylation of specific loci such as NPTX2，Edaradd,Tom1L1 showed significant correlation with age in resent studies involving small groups of people after a genome-wide scan. These genes also were involved in cardiovascular disease and neurological disease. In order to provide a novel stratage for the age estimation using biological samples, this study plans to perform real-time quantitative methylation-specific polymerase chain reaction within a large sample from the Han ethnic group in Chongqing focusing on the methylation status of these genes. Based on the data aquired, we would be able to perform statistical analysis and construct regression model. Then the model will be tested to verify its accuracy. One the other hand, we plan to construct cell model which would over express or low express the target gene. Using cell biology and molecular biology technique, we plan to oberserve the morphology change of these cells, and perform FCM, MTT, western blot, immunohistochemistry examine, etc. on the target cells to verify the expression status of the target genes and the signal pathway of senescence process. In this study, we will look into the mechanisms and roles of the target genes in senescence. Further more, we may provide evidence for interventions based on specific epigenetic marks associated with dis

英文关键词： Bio-age；Senescence；DNA methylation；Age estimation；Epigenetics