中科院，华大基因973项目最新文章：长寿表观遗传

　　

　长寿老人，特别是百岁老人，往往能逃避或延缓年龄相关疾病（如心血管疾病、老年痴呆、2型糖尿病及肿瘤等）的侵扰，且百岁老人的后代也能获得类似的生存优势，提示百岁老人可能具有独特的遗传模式逃避或延缓老年疾病的发生。

   然而，近期研究发现长寿老人和普通对照的疾病易感基因位点频率并无显著差别，提示其它遗传因素可能在长寿过程中发挥更重要的作用。表观遗传因子，特别是DNA甲基化，被发现与个体衰老以及年龄相关疾病紧密联系，但DNA甲基化在人类长寿中的作用还不十分清楚。

    为此，中国科学院昆明动物研究所研究员孔庆鹏研究团队肖富辉、何永捍等利用甲基化DNA免疫共沉淀测序(Methylated DNA Immunoprecipitation Sequencing, MeDIP-seq)技术研究了中国四个地区的长寿老人和匹配对照的全基因组DNA甲基化模式，结果发现626个具有显著甲基化差异的区域。

   进一步分析发现与这些差异甲基化区域相关的基因明显富集于衰老相关疾病，包括心血管疾病、2型糖尿病、中风以及阿尔兹海默症等。课题组还比较分析了高加索百岁老人的全基因组甲基化数据，进一步验证了该发现。该项研究表明，长寿老人的确拥有特殊的DNA甲基化模式，可能通过抑制衰老相关疾病易感基因的表达，通过延缓这些疾病的发生，促进长寿性状的产生。

　　研究结果于近期发表于国际期刊PLoS ONE。

　　该研究是与深圳华大基因公司合作完成的，得到了科技部“973”项目、云南省科技厅、中国科学院和国家自然科学基金项目的支持。

原文摘要：

A Genome-Wide Scan Reveals Important Roles of DNA Methylation in Human Longevity by Regulating Age-Related Disease Genes

It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs) were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer’s disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3)] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2)] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity.