Lee Siu Sylvia, Lee Raymond Y N, Fraser Andrew G, Kamath Ravi S, Ahringer Julie, Ruvkun Gary
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
Nat Genet. 2003 Jan;33(1):40-8. doi: 10.1038/ng1056. Epub 2002 Nov 25.
We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity.
我们报告了一项针对5690个秀丽隐杆线虫基因进行的系统性RNA干扰（RNAi）筛选，以寻找能延长寿命的基因失活情况。我们发现，对线粒体功能至关重要的基因是影响秀丽隐杆线虫寿命的主要基因类别。一项经典的遗传筛选鉴定出线粒体亮氨酰-tRNA合成酶基因（lrs-2）中的一个突变，该突变损害了线粒体功能并与更长的寿命相关。线粒体功能受损的长寿线虫ATP含量和氧气消耗较低，但对自由基和其他应激的反应有所不同。这些数据表明，线粒体功能受损的秀丽隐杆线虫寿命延长不能简单地归因于自由基产生减少，这表明代谢与寿命之间存在更复杂的关联。
