The presence of oxygen in the atmosphere is necessary to sustain most life forms on this planet. However, the metabolism of oxygen can be viewed as a double-edged sword. While the reduction of oxygen to water by mitochondria is coupled to a high production of ATP that allows animals to perform tasks of impressive complexity, the incomplete reduction of oxygen at specific locations in mitochondria leads to the production of reactive oxygen species(ROS) that can attack DNA. In recent years, there has been increasing evidence that the production of ROS by mitochondria plays an important role in aging. The field of aging research has benefited greatly from the use of model organisms with relatively short life spans like the nematode C. elegans to elucidate key molecular components of the aging process. The study by Dillin and collaborators examined whether reducing the concentration of various components of the electron transport chain in mitochondria, sites where electrons can leak out and react with oxygen to form ROS, can extend life span in C. elegans. Also, they investigated whether reducing mitochondrial metabolism at different stages of life has the same effect on longevity.
To reduce the concentration of the various electron transport constituents,the authors used RNA interference (RNAi) technology, which allows the silencing of a gene of potential interest. Four groups of nematodes were treated from the time of hatching with RNAi for four different genes encoding mitochondrial respiratory chain components. All the groups displayed a significantly increased life span.
Since it has been suggested that inhibition of the insulin/IGF1 signaling pathway in C. elegans increases life span by decreasing mitochondrial activity, the team tested whether their respiratory chain pathway merges with the insulin/IGF1 pathway to affect longevity. To do so, they took advantage of two mutants of the insulin/IGF1 pathway, both of which have altered life span. The mutants were treated with RNAi for the four respiratory chain components. While an increased life span in the mutants treated with RNAi compared with the untreated mutants would imply that the insulin/IGF1 pathway and the respiratory chain pathway are independent of each other, the absence of an increased longevity would mean that there is cross-talk between the two pathways. The mutants treated with RNAi lived longer, suggesting that the respiratory chain pathway is a novel pathway that influences aging in C. elegans.
The authors then asked whether the respiratory chain pathway plays a key role at a specific stage of life in determining life span. They exposed a group of nematodes to respiratory chain RNAi from the time of hatching until they became young adults, at which stage they re-activated the gene by stopping the RNAi machinery. Intriguingly, even though the re-activation greatly increased the mRNA level of the respiratory chain component in the young adults, it did not shorten their life span to that of wild-type animals. Moreover, a separate group of nematodes exposed to respiratory chain RNAi only during adulthood did not live longer than controls. In conclusion, this paper puts forward the interesting idea that mitochondrial metabolism early in life is a key factor determining life span.