The involvement of mitochondria and the respiratory chain in aging is well established, and reports have uncovered the role of the nervous system in this process. To address whether particular neurons are important in determining longevity, we targeted the genetic components of complex IV and V in the respiratory chain by RNA inhibition (RNAi) in specific subsets of the Drosophila nervous system. We discovered that simultaneous interference in both serotonergic and dopaminergic neurons or selective interference in neurons expressing the serotonin receptor d5-HT1b leads to shortened Drosophila life span. No differences in life span were observed when RNAi was targeted exclusively to dopaminergic neurons or octopamine/tyramine neurons. Neuronal subtype was a very important factor in our experiments, and this study begins to offer clues as to which neurons might mediate longevity in a cell non-autonomous fashion.