Extension of Drosophila Life Span by RNAi of the Mitochondrial Respiratory Chain
Extension of Drosophila Life Span by RNAi of the Mitochondrial Respiratory Chain
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DOI：
10.1016/j.cub.2009.08.016
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发表时间：
2009-10-13
期刊：
影响因子：
9.2
通讯作者：
Walker, David W.
中科院分区：
文献类型：
--
作者：
Copeland, Jeffrey M.;Cho, Jaehyoung;Walker, David W.
背景：长期以来，线粒体被认为在衰老过程中起着重要作用。在线虫中，对线粒体电子传递链(ETC)功能至关重要的基因是影响寿命的主要基因群。然而，有人认为这可能是线虫生物学的一种特性。在本研究中，我们使用体内RNA干扰(RNAi)策略来灭活果蝇的ETC基因，并检测其对寿命的影响。结果：我们报道了编码线粒体呼吸复合体I、III、IV和V的5个基因的RNAi导致果蝇寿命延长。ETC基因表达减少的长寿果蝇并不总是表现出呼吸复合体组装减少或ATP水平降低。此外，长寿并不总是与生育力下降或对自由基生成物百草枯的抵抗力增强相关。仅在成年组织或神经元中靶向两个复杂I基因的RNAi就足以延长寿命。结论：我们的数据表明，线粒体ETC功能在调节动物衰老中的作用在进化上是保守的，也可能在人类中发挥作用。此外，我们的发现表明，ETC基因表达减少的果蝇寿命更长，不能简单地归因于能量生产的减少导致“存活率”的降低。
Background: Mitochondria have long been proposed to play an important role in the aging process. In the nematode Caenorhabditis elegans, genes important for mitochondrial electron transport chain (ETC) function stand out as a principal group of genes affecting life span. However, it has been suggested that this may be a peculiarity of nematode biology. In the present study, we have used an in vivo RNA interference (RNAi) strategy to inactivate ETC genes in Drosophila melanogaster and examine the impact on longevity.Results: Here, we report that RNAi of five genes encoding components of mitochondrial respiratory complexes I, III, IV, and V leads to increased life span in flies. Long-lived flies with reduced expression of ETC genes do not consistently show reduced assembly of respiratory complexes or reduced ATP levels. In addition, extended longevity is not consistently correlated with reduced fertility or increased resistance to the free-radical generator paraquat. Targeted RNAi of two complex I genes in adult tissues or in neurons alone is sufficient to extend life span.Conclusions: Our data suggest that the role of mitochondrial ETC function in modulating animal aging is evolutionarily conserved and might also operate in humans. Furthermore, our findings suggest that the longer life span of flies with reduced ETC gene expression cannot simply be attributed to reduced energy production leading to decreased "rate of living."