Copper Modulation to Effect Yeast Lifespan

The role of copper in yeast\u27s (Saccharomyces cerevisiae) chronological lifespan and the production of reactive oxygen species (ROS) in the mitochondria is not well characterized. The mitochondrial electron transport chain (ETC) machinery is the primary site of superoxide formation, a ROS associated with premature cell aging. A primary defense against ROS is the enzyme superoxide dismutase (Sod1p). This enzyme requires copper and zinc as metal cofactors in the conversion of superoxide to hydrogen peroxide, a less harmful ROS. The aim of this project is to determine the effect of exogenous copper treatment on strains of yeast lacking Sod1p and its copper chaperone, Lys7p. Our results indicate that low levels of exogenous copper (0.25 mM copper sulfate or less in restricted nutrient media) extend yeast chronological lifespan, especially in cells lacking Lys7p. All cell types see a dramatic reduction in lifespan when exogenous copper levels are increased to 2.0 mM copper sulfate or higher. This indicates that a small increase in the amount of copper in the media is beneficial for yeast in these restricted media conditions. Our current studies are to assess protein levels and gene expression of the yeast ETC machinery, as well as ROS levels, to mechanistically understand how exogenous copper in a small dose is contributing to lifespan extension