How does metabolic rate affect age-induced genomic instability?

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There are a myriad of hypothesis to explain the increased incidence of cancer with age. One of the major hypotheses suggests that high metabolic rate leads to increased cellular damage, including events that ultimately lead to cancer. The Gottschling lab discovered that as yeast cells age, they switch to a higher rate of genomic instability. We propose to use new methods developed in the Gottschling lab, to isolate old yeast mother cells, which are analogous to stem cells in metazoans and measure their metabolic rate - using methods developed in the Van Voorhies lab. We will combine this analysis with genetic and physiological alterations to determine whether metabolic rate impacts age-induced genomic instability in old mother yeast cells. This study will address fundamental issues in eukaryotic cells that may explain age-dependent oncogenesis.