中国科学院昆明动物研究所机构知识库

人口老龄化是目前中国乃至全球十分严峻的问题，随着老龄人口的不断增加，中国的社会人口比例发生了巨大的变化，给社会生产力和社会活力带来了严重的影响，长期患病的老年人群给社会医疗和子女们带来了严重的负担。因此人口老龄化问题是一个关乎国计民生、亟需解决的重大问题。长寿老人作为人类健康衰老的典范，他们能延缓甚至规避很多老年疾病，有较低的住院率和较少的住院时间，能健康地老去。因此对长寿人群这个天然的模型进行研究将会为人们认识长寿、健康衰老提供重要的遗传学依据。单核苷酸多态性（SNP）被称为是第三代遗传标记，由于其在人类染色体上分布广泛、数目多且相对稳定，因此在遗传性疾病的研究方面日益受到广大研究者们的青睐。目前已有很多研究证明在日本、意大利、德国、法国和中国的人群中FOXO3的多态性和长寿密切相关，此外FOXO3在其他模式动物比如线虫、果蝇和小鼠中的同系物也曾经被学者证明会影响新陈代谢和寿命长短。因此本研究旨在探索中国长寿家系中SNP的分布模式，同时为了能结合基因的表达数据进一步研究SNP的作用方式，本文我们以样本的转录组数据为研究基础。本课题，我们采集并获得中国海南长寿家系431例外周血样本的转录组数据，其中汉族群体310例，包括133个长寿老人、100个长寿老人的F1后代和77个F1后代配偶，黎族群体121例，包括49个长寿老人、34个长寿老人F1后代和38个F1后代配偶，F1后代配偶与长寿老人没有血缘关系且生活在相同的环境中，在本研究中作为长寿老人的对照。我们在上述转录组数据基础上进行SNP检测分析，发现在长寿老人和对照里存在诸多显著差异的SNP位点（P<0.05），进一步的表达数量性状基因座（eQTL）分析表明部分SNP确实可调控某些基因的表达。结合已发表的常见的老年病的芯片表达数据，发现部分基因在长寿老人和对照、老年病患者和对照里都显著差异表达且差异表达方向相反。综上所述，本研究结果表明长寿老人确实携带一些SNP，它们通过调控基因的表达来抑制一些重大老年疾病的发生，这可能是长寿老人健康长寿的重要原因。

The population aging is more and more serious in China or in the global at now. With the increase of the aging population, the proportion of the population in Chinese society has changed greatly, which has had a serious impact on social productivity and social vitality. The elderly always have age-related disease and they take a serious burden for social care and their children. Therefore, the problem of population aging is a major problem that is vital to the national economy and people's livelihood. As the model of human healthy aging, long-lived individuals always could escape or delay some age-associated diseases and have lower hospitalization rates. Therefore, the study of this natural model of longevity will bring important genetic evidence to the field of aging and longevity.Single nucleotide polymorphism(SNP) is called the third generation genetic marker, it is more and more popular in genetic diseases because it is Widely distributed on human chromosome and relatively stable. Many studies have reveled that the polymorphism of FOXO3 in Japan, Italy, Germany, France and China is closely related to longevity, and the homologue of FOXO3 has been shown to affect metabolism and longevity in other models such as Caenorhabditis elegans, fruit flies and mice. Therefore, we explored the distribution pattern of SNP in Chinese longevity family. At the same time, in order to study the effect of SNP by combining gene expression data, this thesis is based on the transcriptome data.We collected and obtained the transcriptome data of 331 samples’ peripheral blood from the longevity family in hainan, China, including 210 Han samples(133 long-lived individuals,100 long-lived individuals’ F1 offspring and 77 spouses of their F1 offspring), 121 Li samples(49 long-lived individuals,34 long-lived individuals’ F1 offspring and 38 spouses of their F1 offspring). The spouses of F1 offspring were considered as control group because they did not have blood relationship with long-lived individuals but they lived in same environment with them. The transcriptome data of all samples was obtained by RNA-Seq, and then we detected and analyzed the SNPs on the basis of transcriptome data, our analysis showed there were SNPs were significantly different in long-lived individuals and controls(P<0.05). Further expression Quantitative Trait Loci(eQTL) analysis showed that some SNPs could regulate the expression of related genes. For these genes, we combined with chip expression data of common age-related disease for further comparative analysis, we showed that some of these genes were significantly differentially expressed in long-lived individuals and controls, elderly patients and controls, and the direction of gene expression was on the contrary. In sum up, our results indicated that long-lived individuals did carry some SNPs, which could inhibit the occurrence of major diseases by regulating gene expression, it may be an important cause of longevity and health.