The phenotypic enhancement of longevity through a variety of environmental treatments, including dietary manipulations, has been observed in various species of animals, both vertebrate and invertebrate. Elucidating the mechanisms underlying such effects has provided insights into the physiological processes contributing to the determination of lifespan. Here, we report the enhancement of longevity in adult Drosophila melanogaster maintained on food supplemented with urea, a metabolic waste product occurring naturally in Drosophila cultures, especially at high larval densities. The impact of urea on longevity is shown to be through a decrease in the age-independent parameter (A) of the Gompertz equation, rather than the age-dependent parameter (alpha), which reflects the "rate of aging." We also present evidence suggesting that the urea-induced increase in longevity is mediated exclusively through a reduction in some aspect(s) of reproduction in adult flies maintained on urea-supplemented food.

Oviposition preference for urea-supplemented food was assayed by simultaneous choice trials on five pairs of closely related laboratory populations of Drosophila melanogaster. Each pair of populations had been derived from a separate ancestral population about 85 generations prior to this study. One population in each pair had been subjected to selection for larval tolerance to the toxic effects of urea; the other population served as a control. Considerable variation in oviposition preference was seen both within and among populations, with four of the ten populations showing a significant mean preference for urea-supplemented food. The degree of specificity shown by individual females was surprisingly high, leading to a bi-modal distribution of oviposition preference in some populations. Overall, selection for larval tolerance to urea did not significantly affect oviposition preference. However, the data indicated that pair-wise comparisons between randomly selected populations from the two larval selection regimes would lead to a range of possible outcomes, suggesting, in several cases, that selection for larval urea tolerance had led to significant differentiation of adult oviposition preference for urea in one or the other direction. The results, therefore, highlight the importance of population level replication and caution against the practice, common in ecological studies, of assaying oviposition preference in two populations that utilize different hosts in nature, and then drawing broad evolutionary inferences from the results.

BACKGROUND: Nuclear receptor subfamily 1, group I, member 2 (NR1I2), commonly known as steroid and xenobiotic receptor (SXR) in humans, is a key ligand-dependent transcription factor responsible for the regulation of xenobiotic, steroid, and bile acid metabolism. The ligand-binding domain is principally responsible for species-specific activation of NR1I2 in response to xenobiotic exposure. OBJECTIVES: Our objective in this study was to create a common framework for screening NR1I2 orthologs from a variety of model species against environmentally relevant xenobiotics and to evaluate the results in light of using these species as predictors of xenobiotic disposition and for assessment of environmental health risk. METHODS: Sixteen chimeric fusion plasmid vectors expressing the Gal4 DNA-binding domain and species-specific NR1I2 ligand-binding domain were screened for activation against a spectrum of 27 xenobiotic compounds using a standardized cotransfection receptor activation assay. RESULTS: NR1I2 orthologs were activated by various ligands in a dose-dependent manner. Closely related species show broadly similar patterns of activation; however, considerable variation to individual compounds exists, even among species varying in only a few amino acid residues. CONCLUSIONS: Interspecies variation in NR1I2 activation by various ligands can be screened through the use of in vitro NR1I2 activation assays and should be taken into account when choosing appropriate animal models for assessing environmental health risk.