[新聞轉載] Cisd2基因 藏有長壽密碼
http://www.libertytimes.com.tw/2009/new/may/16/today-t1.htm
2009-5-16 Cisd2基因 藏有長壽密碼
陽明大學副教授蔡亭芬（右二）帶領博士生陳怡帆（左一）與國衛院研究員蔡世峰（右一
），從毛髮變白、眼睛變凸的小黑鼠身上，成功證實Cisd2基因調控哺乳動物壽命的長短
，研究論文被國際知名期刊「基因與發育」（Genes & Development）選作五月十四日最
新一期封面故事。（記者謝文華攝）
〔記者謝文華／台北報導〕想要長生不老，真的有可能嗎？陽明大學生命科學系暨基因體
科學所副教授蔡亭芬帶領的研究團隊，原本要尋找肝癌基因，卻首次證明了Cisd2基因調
控哺乳動物壽命的長短 。
陽明團隊 躍上國際期刊封面
少了Cisd2基因的小黑鼠，不僅體型瘦小，而且髮蒼蒼、視茫茫，提早衰老、壽命減半。
團隊正在研究如果加倍移植Cisd2蛋白，小黑鼠是否會更長壽？
由於不論是低等或高等生物同樣都擁有Cisd2基因，陽明大學校長吳妍華振奮地說：「未
來若證實透過調控Cisd2可以延長壽命，說不定人類真的可以長生不老！」這篇成功破解
老化遺傳基因密碼的研究，刊登在國際重要期刊「基因與發育」，而且還是首次有台灣研
究登上期刊封面，備受矚目。
研究顯示，剔除Cisd2基因的小黑鼠，在四到八週（約人類十五至二十五歲）後，不僅體
型比同胎兄弟瘦小，還長出白毛、不停顫抖、喘不過氣；晚期眼睛凸出白濁、骨質疏鬆、
駝背、皮膚鬆弛，十足像個「小老頭」。這群小黑鼠當中有四十％在七個月死亡，比野生
鼠平均能活兩年的生命周期，明顯短命許多。
蔡亭芬表示，Cisd2是影響粒線體結構完整的關鍵，粒線體是細胞製造能量的工廠，對肌
肉和神經細胞尤其重要。一旦缺少Cisd2時，粒線體破損、功能失調，老化徵狀接踵而來
。
少了Cisd2 小黑鼠早衰短命
二○○一年，哈佛大學曾針對一百三十七個長壽家庭、三百多名人瑞基因分析，發現長壽
基因可能位於人類第四號染色體；榮總、陽明團隊另在定序第四號染色體基因時，發現了
Cisd2。
蔡亭芬說，第四號染色體有幾百個基因，國家衛生研究院研究員蔡世峰判斷，從低等果蠅
、爬蟲類，到高等哺乳類、人類等生物，都有Cisd2，且在演化過程中留存，顯示它肯定
掌管了某些重要功能，促使研究團隊找到對的切點。
無心插柳 意外窺知抗老秘密
蔡亭芬的團隊原本要找肝癌基因，受挫近三年，但在第一作者、陽明大學生科系暨基因體
所博士生陳怡帆鍥而不捨地觀察到小黑鼠老化的生理現象，意外揭開Cisd2基因在壽命長
短與老化過程中扮演要角，「無心插柳」卻因而窺知了抗老秘密！
蔡亭芬指出，後續將借助美國、日本的長壽家族資料庫，分析人瑞的Cisd2，希望有一天
能夠找出人類長生不老之鑰。
蔡亭芬也強調，使用抗氧化劑活化Cisd2的小黑鼠，代謝功能好，雄鼠還能在十二個月後
罕見地讓雌鼠受孕。想要提早抗老的民眾，多攝取含豐富抗氧化物的新鮮蔬果準沒錯。
http://genesdev.cshlp.org/content/23/10/1183.abstract
Cisd2 deficiency drives premature aging and causes mitochondria-mediated
defects in mice
1. Yi-Fan Chen1,
2. Cheng-Heng Kao2,
3. Ya-Ting Chen1,3,
4. Chih-Hao Wang4,
5. Chia-Yu Wu1,
6. Ching-Yen Tsai1,
7. Fu-Chin Liu5,
8. Chu-Wen Yang6,
9. Yau-Huei Wei4,
10. Ming-Ta Hsu4,
11. Shih-Feng Tsai1,3 and
12. Ting-Fen Tsai1,3,7
+Author Affiliations
1.
1Department of Life Sciences and Institute of Genome Sciences, National
Yang-Ming University, Taipei 112, Taiwan;
2.
2Center of General Education, Chang Gung University, Taoyuan 333,
Taiwan;
3.
3Division of Molecular and Genomic Medicine, National Health Research
Institutes, Zhunan, Miaoli County 350, Taiwan;
4.
4Institute of Biochemistry and Molecular Biology, National Yang-Ming
University, Taipei 112, Taiwan;
5.
5Institute of Neuroscience, National Yang-Ming University, Taipei 112,
Taiwan;
6.
6Department of Microbiology, Soochow University, Taipei 111, Taiwan;
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.
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