The proposed research has two overall aims: (1) to further understand postponed aging in Drosophila; and (2) to use Drosophila to develop methods for postponing aging in other species. The Program Project consists of a Core and five Component Projects, as follows. The core would maintain D. melanogaster stocks with postponed aging, stocks that all Projects would use, except Project 3. Project 1 concerns genotype-by-environment interactions involving nutrition and genetically postponed aging. Nutrition would be varied during selection for postponed aging and selection for starvation resistance. Project 2 is concerned with the physiological analysis of the correlates of postponed aging. This study would particularly emphasize those relationships between metabolic resource allocation, response to dietary manipulation, and aging that characterize postponed-aging and stress-resistant stocks. Project 3 addresses the problem of generalizing from one species to another, within a defined taxonomic group. the proposal is to select for postponed aging upon five Drosophila species, including D. melanogaster, and then test for physiological and genetic parallels in the responses of the five species. Breeding experiments with D. melanogaster would be performed to compare the effects of alternative electrophoretic genotypes on aging phenotypes. Project 4 is concerned with the effects of linkage disequilibrium and finite population size on the population genetics of postponed aging. Mathematical and experimental work would analyze the extent of linkage disequilibrium arising from selection for postponed aging, the experimental work concentrating on the Cu,Zn superoxide dismutase locus, which has undergone allele frequency change in the course of selection. Project 5 would use protein microsequencing, probing, and cloning to identify loci that produce the proteins that have already been found to be associated with postponed aging from two-dimensional protein electrophoresis.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Biological and Clinical Aging Review Committee (BCA)
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University of California Irvine
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