Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Aging of humans is due to a lifelong build-up of unrepaired damage to cellular macromolecules and organelles. Progressive accumulation of such damage impairs normal functioning of the entire organism, thereby increasing a risk of disease and death. Therefore, the pace of aging depends on the rates and spatiotemporal organization of cellular processes producing the damage and repairing it. We use the yeast Saccharomyces cerevisiae for defining the mechanisms of aging, which in this unicellular organism is mechanistically similar to cellular aging in multicellular organisms. We elucidate how various interventions alter the rates of numerous cellular processes and their organization in space and time and how such alterations affect longevity. Recent work from our laboratory has shown that a number of cellular processes, which we call modules, are integrated into a longevity network. Our findings imply that, by setting up (in a diet- and genotype-dependent fashion) the rates of the processes taking place within each of the network's modules during early adulthood, yeast establish a particular configuration of the network that specifies the pace of their aging during late adulthood. Our study suggests a concept of the longevity control system governing progression through a series of checkpoints that occur at various stages of life. We have recently revealed several small molecules that significantly delay aging of yeast. The experiments that are now proposed are aimed at elucidating the molecular mechanisms regulating longevity. I will examine how a novel anti-aging molecule that we discovered increases life span by modulating longevity- and disease-related processes in cellular organelles called mitochondria. This knowledge is fundamental to understand the molecular defects underlying numerous disorders of aging, including neurodegenerative diseases caused by mitochondrial dysfunction, and lays the foundation for future therapeutic approaches to their treatment.