application): Until recently, mortality for nearly all species was believed to increase exponentially at older ages. Several reports have now shown that in humans, Drosophila, reedfiles, and nematodes mortality levels off and, in some instances, even declines at advanced ages. However, it is not yet clear whether the observed mortality patterns are due to a leveling off of the rate of senescence in each individual or to environmental or genetic heterogeneity within the population. Baker s yeast (Saccharomyces cerevisiae) is a highly studied unicellular fungus with a completely sequenced genome which shares remarkable similarities with human cells and has a lifespan of more than 30 days in stationary phase. These features and the established and straightforward genetic manipulations available make yeast a valuable model to study mortality trajectories in eukaryotes. The goal of this proposed research is to study the age-specific mortality of large populations of S. cerevisiae, to isolate long-lived mutants, and to establish whether this unicellular eukaryote undergoes age-dependent deteriorative physiological changes analogous to those seen in higher eukaryotes. The mortality and physiological changes for billions of organisms will be studied in a highly controlled environment and established yeast techniques will be used to isolate longlived mutanrs. These experiments will extend biodemographical studies to the fungal kingdom, will give further test to the hypothesis that mortality decelerates at advanced ages, and will provide insights on the mechanisms that determine longevity in lower as well as higher eukaryotes. The large size of the initial yeast population will allow the study of mortality patterns and the isolation of long-lived mutants when an exceedingly small fraction of the organisms are still alive.
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