Extended life-span conferred by cotransporter gene mutations in Drosophila
Extended life-span conferred by cotransporter gene mutations in Drosophila
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DOI：
10.1126/science.290.5499.2137
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发表时间：
2000-12-15
期刊：
影响因子：
56.9
通讯作者：
Helfand, SL
中科院分区：
文献类型：
--
作者：
Rogina, B;Reenan, RA;Helfand, SL
衰老是由基因决定和环境调节的。在一项关于成年果蝇（Drosophila melanogaster）寿命的研究中，我们发现，单个基因中的五个独立的P元件插入突变导致成年平均寿命几乎翻了一番，而生育力或体力活动却没有下降。序列分析显示，这个名为Indy（意为“我还没死”）的基因产物与哺乳动物二羧酸钠协同转运蛋白（一种转运克雷布斯循环中间产物的膜蛋白）关系最为密切。Indy在脂肪体、中肠和卵母细胞中表达最丰富：这是果蝇中间代谢的主要部位。P元素的切除导致恢复到正常寿命。这些突变可能会产生一种代谢状态，模仿热量限制，这已被证明可以延长寿命。
Aging is genetically determined and environmentally modulated. In a study of Longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult Life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal Life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend Life-span.