The proposed research is concerned with genetically-postponed senescence in Drosophila melanogaster. Mammalian senescence does not readily respond to simple types of environmental manipulation, while interspecific differences in mammalian senescence, as measured by maximum longevity for example, are substantial. Evolutionary changes to mammalian physiology can evidently postpone senescence substantially. This suggests that biomedical research should be directed toward understanding how evolution can genetically postpone senescence, in the hope of discovering how to mimic the effects of such genetic change biochemically. Since little is known of genetically-postponed senescence in any species, it is proposed that initial research concentrate on the most tractable animal species from the standpoints of evolutionary manipulation and genetic analysis, such as D. melanogaster. Stocks of this species with genetically-postponed senescence have already been produced and subjected to some evolutionary, physiological, and genetic analysis. Further analysis requires the creation of stocks which have been genetically fixed for the alleles affecting specific physiological mechanisms of postponed senescence, which can be done by artificial selection on characters which enhance adult survival, specifically resistance to starvation, desiccation, and low-levels of ambient ethanol. Once these stocks have been created, it is proposed that: (i) a specific locus affecting starvation-resistance be mapped using electrophoretic markers; (ii) the genetic relationship between fitness and postponed senescence be determined by sorting out the distinct loci and physiological mechanisms which postpone senescence into two classes, those that have antagonistic pleitropic effects on fitness-components and those that do not have such effects; and (iii) further physiological analyses be carried out with a view to determining the molecular basis of the physiological mechanisms of postponed senescence.
