Mitochondrial ROS production correlates with, but does not directly regulate lifespan in drosophila
Mitochondrial ROS production correlates with, but does not directly regulate lifespan in drosophila
复制标题
DOI：
10.18632/aging.100137
复制
发表时间：
2010-04-01
期刊：
影响因子：
5.2
通讯作者：
Jacobs, Howard T.
中科院分区：
文献类型：
--
作者：
Sanz, Alberto;Fernandez-Ayala, Daniel J. M.;Jacobs, Howard T.
线粒体自由基衰老理论（MFRTA）是目前用于解释衰老最广泛接受的理论之一。根据 MFRTA 可以做出三个基本预测：长寿的个体或物种应该比短命的个体或物种产生更少的线粒体活性氧 (mtROS)； mtROS 产量的减少将延长寿命； mtROS 产量的增加会缩短寿命。可以添加进一步的第四个预测：如果 ROS 控制寿命，则不可能通过选择来分离这些参数。这些预测已在黑腹果蝇中得到检验。首先，我们研究了三种野生型果蝇菌株（Oregon R、Canton S 和 Dahomey）的 mtROS 产生水平和寿命。俄勒冈州 R 果蝇寿命最长，产生的 mtROS 明显少于坎顿 S 和达荷美果蝇。因此，这些结果与第一个预测一致。使用表达海鞘替代氧化酶（AOX）的新转基因果蝇模型来测试第二个预测。在真菌和植物中，AOX 表达调节自由基的产生和寿命。在果蝇中，AOX 表达会减少 mtROS 的产生，但不会延长寿命。这一结果与 MFRTA 的第二个预测相矛盾。第三个预测在果蝇基因 dj-1 beta 突变体中进行了测试。这些果蝇的特征是与年龄相关的运动功能下降和 mtROS 产生水平增加。然而，dj-1 beta 突变果蝇并没有表现出寿命缩短，这又与 MFRTA 相矛盾。在我们的最终实验中，我们在 OR 核背景中使用了具有 DAH 线粒体 DNA 的果蝇，在 DAH 核背景中使用了 OR 线粒体 DNA。由此看来，线粒体 DNA 并不控制自由基的产生，但它确实独立于 mtROS 的产生而决定女性的寿命。总之，这些结果并不能系统地支持 MFRTA 的预测。因此，MFRTA 应进行修订以适应这些发现。
The Mitochondrial Free Radical Theory of Aging (MFRTA) is currently one of the most widely accepted theories used to explain aging. From MFRTA three basic predictions can be made: long-lived individuals or species should produce fewer mitochondrial Reactive Oxygen Species (mtROS) than short-lived individuals or species; a decrease in mtROS production will increase lifespan; and an increase in mtROS production will decrease lifespan. It is possible to add a further fourth prediction: if ROS is controlling longevity separating these parameters through selection would be impossible. These predictions have been tested in Drosophila melanogaster. Firstly, we studied levels of mtROS production and lifespan of three wild-type strains of Drosophila, Oregon R, Canton S and Dahomey. Oregon R flies live the longest and produce significantly fewer mtROS than both Canton S and Dahomey. These results are therefore in accordance with the first prediction. A new transgenic Drosophila model expressing the Ciona intestinalis Alternative Oxidase (AOX) was used to test the second prediction. In fungi and plants, AOX expression regulates both free radical production and lifespan. In Drosophila, AOX expression decreases mtROS production, but does not increase lifespan. This result contradicts the second prediction of MFRTA. The third prediction was tested in flies mutant for the gene dj-1 beta. These flies are characterized by an age associated decline in locomotor function and increased levels of mtROS production. Nevertheless, dj-1 beta mutant flies do not display decreased lifespan, which again is in contradiction with MFRTA. In our final experiment we utilized flies with DAH mitochondrial DNA in an OR nuclear background, and OR mitochondrial DNA in DAH nuclear background. From this, Mitochondrial DNA does not control free radical production, but it does determine longevity of females independently of mtROS production. In summary, these results do not systematically support the predictions of the MFRTA. Accordingly, MFRTA should be revised to accommodate these findings.