Extension of Drosophila Life Span by RNAi of the Mitochondrial Respiratory Chain

Abstract

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. 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. 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."