Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
Ann N Y Acad Sci. 2010 Jul;1201:58-64. doi: 10.1111/j.1749-6632.2010.05619.x.
CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is an evolutionarily conserved novel gene. Recently, we have demonstrated that CISD2 is involved in mammalian lifespan control; this work also establishes WFS2 as a mitochondria-mediated disorder and effectively links CISD2 gene function, mitochondrial integrity, and aging in mammals. In wild-type mice, the expression levels of CISD2 decrease in an age-dependent manner during the naturally aging process; this correlates with mitochondrial breakdown and parallels the development of an aged phenotype. Future work will examine how the CISD2 knockout mouse helps us to understand WFS2 pathogenesis, as well as exploring the potential effects of increased CISD2 expression. In addition, it will be of great interest to compare gene activity and/or protein function between normal human populations and long-lived centenarian groups. Together, human and mouse genetic studies should provide evidence as to whether CISD2 is a "master gene" for extreme old age.
CISD2 是沃尔夫拉姆综合征 2 （WFS2）的致病基因，是一个进化上保守的新基因。最近，我们已经证明 CISD2 参与了哺乳动物寿命的控制；这项工作还将 WFS2 确定为一种线粒体介导的疾病，并有效地将 CISD2 基因功能、线粒体完整性和哺乳动物衰老联系起来。在野生型小鼠中，CISD2 的表达水平在自然衰老过程中随年龄呈依赖性下降；这与线粒体崩溃相关，与老年表型的发展平行。未来的工作将研究 CISD2 敲除小鼠如何帮助我们理解 WFS2 的发病机制，并探索增加 CISD2 表达的潜在影响。此外，比较正常人群和长寿百岁老人群体之间的基因活性和/或蛋白质功能将非常有趣。总之，人类和小鼠的遗传研究应该为 CISD2 是否是“长寿的主基因”提供证据。
