Brandt Bernd W, Zwaan Bas J, Beekman Marian, Westendorp Rudi G J, Slagboom P Eline
Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, The Netherlands.
Bioessays. 2005 Mar;27(3):339-46. doi: 10.1002/bies.20161.
Studies to find genes that affect maximum lifespan aim at identifying important determinants of ageing that may be universal across species. Model organisms show insulin signalling can play an important role in ageing. In view of insulin resistance, such loci can also be important in human ageing and health. The study of long-lived humans and their children points to the relevance of lipoprotein profiles and particle size for longevity. If ageing pathways are conserved, then the genes mediating such pathways may also be conserved. Cross-species sequence comparisons of potential longevity loci may reveal whether the pathways that they represent are central themes in lifespan regulation. Using bioinformatic tools, we performed a sequence comparison of the genes involved in lipid metabolism identified in humans as potential longevity loci. This analysis revealed that lipid storage and transport may be a common theme related to longevity in humans, honeybees and nematodes. Here, the vitellogenin family emerges as a potential key connection between lipid metabolism and the insulin/IGF-1 signalling pathway.
寻找影响最大寿命的基因的研究旨在确定可能在物种间普遍存在的衰老重要决定因素。模式生物表明胰岛素信号传导在衰老过程中可发挥重要作用。鉴于胰岛素抵抗,此类基因座在人类衰老和健康方面也可能很重要。对长寿人群及其子女的研究表明脂蛋白谱和颗粒大小与长寿有关。如果衰老途径是保守的,那么介导此类途径的基因也可能是保守的。对潜在长寿基因座进行跨物种序列比较,可能会揭示它们所代表的途径是否是寿命调节的核心主题。我们使用生物信息学工具对在人类中鉴定为潜在长寿基因座的参与脂质代谢的基因进行了序列比较。该分析表明脂质储存和转运可能是与人类、蜜蜂和线虫长寿相关的一个共同主题。在此,卵黄蛋白原家族成为脂质代谢与胰岛素/胰岛素样生长因子-1信号通路之间潜在的关键联系。