Fred Hutchinson Cancer Research Center
Replicative senescence in S. cerevisia.
The yeast Saccharomyces cerevisiae has become recognized as a model system for studying replicative senescence in eukaryotes. It permits easy genetic and physiological manipulations of cells, and a chance to examine aging cells in a homogeneous population. However, current methods of aging analysis in yeast are cumbersome and do not take advantage of its strengths as a microbiological organism: the ability to carry out intensive screens or selections based on colony formation. We propose to develop colony-based assays for yeast life span that will enhance the study of genetic and environmental contributions to aging in S. cerevisiae.
Once in hand, we will use these new assays to identify the processes that define the limit of life span for a particular cell, given its genetic make-up, environmental situation and physiological status. We postulate that given these three conditions, there will be a number of distinct mechanistic pathways by which cells come to the end of their replicative potential. A first step in understanding aging will be to identify the pathways and how the three conditions determine which pathway defines the limit of life span. A much longer-term goal of these studies is to understand the molecular basis by which each pathway limits life span.
We have also become interested in the well-documented connection between advanced age and an increased frequency of cancer in humans. Nearly 80% of all cancers are diagnosed at ages 55 and older, with a lifetime risk that 1 out of 2 men and 1 out of 3 women will die from cancer. We have sought to better understand this correlation by asking whether aging yeast cells might serve as a model system for dissecting a mechanism behind this phenomenon.