Harris, Nicholas Lionel; (2002) Stress resistance and ageing in Saccharomyces cerevisiae. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The budding yeast, Saccharomyces cerevisiae, can be used as a model in which the processes behind ageing can be investigated. Yeast life span can be determined in two ways, i) the number of buds produced by an actively dividing mother cell can be counted as a measure of a yeast's budding life span, ii) the viability over time of cells arrested in GO can be recorded as a measure of yeast's chronological life span. As is the case for Drosophila and C. elegans increasing the cellular stress resistance and antioxidant scavenging capabilities of yeast extends the chronological life span. By increasing the stress resistance of cerevisiae through the overactivation of the heat shock response resulting from defects in the Hsp90 chaperone the chronological ageing of GO arrested cells was extended. The budding potential of these cells however was not increased. Extensions to the chronological lifespan of yeast adapted torespiratory growth was achieved with the overexpression of the superoxide dismutase enzymes, Cu,Zn-Sod and Mn-Sod, as well as catalase. A two-fold extension to chronological lifespan extension was observed in cells with increased Cu,Zn-Sod activity. In this strain levels of free radicals are low and the onset of total cellular protein oxidation, which coincides with a dramatic reduction in cellular viability, is delayed. The generation of free radicals during respiration is therefore a limiting factor for longevity. Over expressions of the free radical scavenging enzymes did not increase the budding potential of yeast cells. Despite the benefits for chronological survival gained from the overexpression of Mn-Sod, a disruption in mitochondrial morphology and inheritance in this strain leads to a reduced number of buds a mother cell could produce. A future goal for yeast ageing research is the identification of novel pathways involved in the determination of lifespan. The final part of this study included the development of a system by which the Euroscarf collection of deleted yeast strains can be screened for long lived mutants.

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