胰岛素/胰岛素样生长因子-1信号通路相关基因多态性与长寿的遗传关联分析及功能研究

Insulin/IGF-1 Signaling(IIS) pathway simultaneously participates in the formation of several pathways related to biological processes like cell energy metabolism, fat metabolism, and autophagy. Experiments with several animal models proved that IIS pathway is related to aging. Studies on the relationship between single genes in IIS pathway and human longevity, including the applicants’ former studies, suggested the potential relevance between the genomic variation in IIS pathway and longevity. Hainan, known as the Longevity Island, is the province with the largest centenarian density (13.22 per 100 thousands) in China. Previously we collected and sorted the precious longevity population genetic resources, established a sample library. Base on the previous work, in this study we plan to apply a 3-phase analysis of “Tag SNP association study--Sanger re-sequecing study--Functional study” on 6 key genes in IIS pathway, systematically analyze the genetic linkage and molecular mechanism between variations of IIS pathway and longevity, then provide support for clarifying the genetic mechanism of longevity.

胰岛素/胰岛素样生长因子-1信号通路（Insulin/IGF-1 signaling pathway，IIS），同时参与了与细胞能量代谢、脂肪代谢、细胞自噬等多个生物学过程相关的多个通路的组成，多种模式生物中证明IIS通路与衰老相关。包括申请人在内的以往针对该通路中单个基因与人类长寿的多项研究已提示该通路相关基因多态与长寿的潜在相关性。海南是我国百岁老人密度最大的省份，百岁老人的人口密度达13.22人/10万人，被称为长寿岛。我们前期已经收集整理了珍贵的长寿人群遗传资源，并建立了相应样本库。在前期工作基础上，本研究计划对IIS通路中的6个关键基因采用“标签SNP关联分析筛选— 上下游序列重测序— 细胞生物学功能机制实验” 三个研究阶段的分析，系统研究IIS通路基因多态与长寿的遗传关联及分子机制，为阐明长寿的遗传学机理提供支持。