Grant: Discovery Grants Program - Individual

The free radical theory of aging suggests that aging results from an accumulation of damage to cellular components, resulting in cell death, tissue and organ failure, and eventually the death of the organism. The source of this damage is believed to be reactive oxygen species (ROS), produced as toxic byproducts of normal metabolism. ROS are implicated in a variety of age-related disorders including diabetes, cancer, atherosclerosis, and neurodegenerative disease. ROS are highly reactive molecules capable of damaging cellular components including DNA, proteins, and membranes. As well as directly damaging cells, ROS play critical physiological roles by modulating many of the cell signaling pathways which control gene expression. Unfortunately, most of our insights into the biological roles of ROS have been derived from studies in cell culture systems, and their significance to functioning tissue in an intact whole organism remains uncertain. ROS metabolizing enzymes, such as Cu/Zn superoxide dismutase (SOD1) and catalase (CAT), are the first line of defense against elevated levels of ROS. In the fruit fly Drosophila melanogaster, genetic strains exist which lack these enzymes, and consequently show reduced longevity and develop a set of physiological disorders reminiscent of human age-related diseases. My research program uses strains lacking SOD1 to investigate the damaging effects of ROS in specific tissues of a complete organism. We are investigating the hypothesis that the inability of SOD1 mutants to properly eliminate ROS may result in disruption of cell signaling, and that the resulting changes in gene expression may be the ultimate cause of the pathologies observed in SOD1 mutants. Understanding the fundamental mechanisms by which ROS cause cell and tissue dysfunction will provide insight into the causes of age-related disease in all organisms, including humans. Such diseases represent a huge burden on the health, welfare, and economic prospects of Canadians. Considering the demographic profile of the Canadian population, basic research that promises to diminish this burden is essential.