Genetic variation for life span, resistance to paraquat, and spontaneous activity in unselected populations of Drosophila melanogaster: implications for transgenic rescue of life span.

Genetic variation in adult life span, resistance to paraquat, resistance to DDT, and spontaneous flying activity were measured in 138 recombinant inbred lines of Drosophila melanogaster. We find that the phenotypic correlation between life span and resistance to an exogenous oxidizing agent is positive, though weak, and that there is little correlation between the two traits at the level of quantitative trait loci (QTLs). The sign of the life span-resistance correlation is haplotype-specific, suggesting a high degree of statistical interaction and dependence on genetic background. Because of the genotype-specificity in the relationship between life span and resistance phenotypes, interventions to extend life span by overexpression of antioxidant enzymes are likely to produce strain-specific results. These observations are in general agreement with the "genetic rescue" hypothesis of Sohal et al. [Sohal, R.S., Mockett, R.J., Orr, W.C., 2002. Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic. Biol. Med. 33, 575-586.], though we emphasize that such statistical interaction is a normal feature of standing genetic variation, and does not imply that some genotypes are pathological. Ad hoc observation of spontaneous flying activity 5 days after emergence proved to be a much better predictor of life span than resistance to an exogenous oxidant in these populations.