Targeted neuronal gene expression and longevity in Drosophila

Earlier studies from this laboratory have shown that in the insect, Drosophila melanogaster, the motorneuron is an important cellular nexus between the metabolism of reactive oxygen species (ROS) and adult lifespan. This was demonstrated by experiments in which expression of CuZn SOD (SOD1) specifically in motorneurons was shown to extend the mean and maximum adult lifespans to 140% of normal, and to rescue the majority of deliterious phenotypes displayed by SOD1-null mutants. We have interpreted these results to mean either that the lifespan of the organism is normally limited by the functional lifespan of this post-mitotic cell type, or that ROS metabolism in motorneurons affects organismic lifespan via a systemic, perhaps neuroendocrine, signaling mechanism. We have now extended these studies to ask: (i) whether expression of catalase (CAT) or of the mitochondrially-localized Mn SOD (SOD2) in motorneurons, either singly or in combination with SOD1, have similar effects on lifespan; (ii) if expression of SOD2 can rescue SOD1-null mutant phenotypes; and (iii) if ROS metabolism in cell types other than motorneurons has significant impact on aging and lifespan determination.