蔡亭芬封面文章 破解长寿基因（图）

　　

生物通报道，台湾阳明大学生科系基因所蔡亭芬教授领衔的长寿基因研究文章发表在冷泉港旗下的《Genes & Development》上，文章Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice被收录为本期的封面文章。蔡亭芬教授首次证实Cisd2基因是调控哺乳动物寿命长短的基因。

 

参与研究的团队还包括长庚大学，东吴大学和国家卫生研究院的研究人员。

 

 

研究团队与《Genes & Development》封面合影 左起蔡亭芬、蔡世峰，博士生陈怡帆

 

早在2001年，美国哈佛大学曾利用一百多个长寿的家族做分析，结果发现在人类第四号染色体的长臂上可能有决定人类长寿与否的基因。后来，研究人员发现一个新颖的基因就位于这个长寿的染色体区域内，现在就命名为Cisd2。Cisd2高度保守，从低等动物到高等动物都有这个基因。

 

蔡亭芬发现，把小黑鼠的Cisd2基因剔除后，细胞里制造能量的工厂粒腺体就会开始破损，使提供能量的小分子ATP供应不足，进而导致全身性的肌肉萎缩，神经退化，成为视茫茫、发苍苍，齿牙动摇的老人。剔除Cisd2的小黑鼠不仅比同胎兄弟瘦小，且十个月大时，头顶就开始出现白毛，不停颤抖，紧张时，会像老人般喘不过气，成为一只短命鼠。

 

生物通推荐原文检索：Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice

【Abstract】

CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Significantly, the CISD2 gene is located on human chromosome 4q, where a genetic component for longevity maps. Here we show for the first time that CISD2 is involved in mammalian life-span control. Cisd2 deficiency in mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, and these events precede the two earliest manifestations of nerve and muscle degeneration; together, they lead to a panel of phenotypic features suggestive of premature aging. Our study also reveals that Cisd2 is primarily localized in the mitochondria and that mitochondrial degeneration appears to have a direct phenotypic consequence that triggers the accelerated aging process in Cisd2 knockout mice; furthermore, mitochondrial degeneration exacerbates with age, and the autophagy increases in parallel to the development of the premature aging phenotype. Additionally, our Cisd2 knockout mouse work provides strong evidence supporting an earlier clinical hypothesis that WFS is in part a mitochondria-mediated disorder; specifically, we propose that mutation of CISD2 causes the mitochondria-mediated disorder WFS2 in humans. Thus, this mutant mouse provides an animal model for mechanistic investigation of Cisd2 protein function and help with a pathophysiological understanding of WFS2.