Aging can be described as a program of gene expression, in which groups of genes are turned on and off in a progressive and genetically determined (or partially genetically determined) fashion. Our goal is to create and accurate, complete expression profile of aging populations of yeast cells, so that we can identify clusters of genes with similar transcription patterns (regulons), defining the aging program. The determination of this ordered sequence of transcriptional changes in normal aging can be used to evaluate whether life span changes in mutants affecting genomic stability and chromatin structure include any aging component(s). We predict that there wilt be found a lifelong program with additional induction of genetic programs that respond to damage to macromolecules that would appear late in the life time. We will examine mutants with a deletion of the gene for silent information regulator Sir2 and with one extra copy of this gene on its own promoter (since an overdose is toxic). The deletion has a shorter life span and the extra copy strain has a significantly longer life span. We predict contraction and expansion of the part of the program(s) specific to aging in these strains. We will also examine a deletion and an extra copy strain for Sir3 with similar but less dramatic effects on life spans. We will look at a deletion for Sgs1 gene, since that helicase is known to shorten life span but is thought to do so by a combination mechanism. The gene expression patterns obtained will be compared with those known to be induced by damage to DNA and proteins. We will use the data from wild type in an extensive data analysis, looking for coregulated genes, then seeking to identify the probable bases of their coregulation. We will seek to decide whether aging seems to result from an ongoing unitary genetic program or from one program overall with other cascades that respond to damaged macromolecules superimposed upon it. We will look for regulatory sequences that match the regulons identified using GeneSpring, and will identify transcription factors that may correspond to these sequences for future study. Finally we will compare our results with those obtained for other organisms undergoing aging, to examine the extent to which cellular aging in the sense in which yeast experience it may contribute to the aging of higher organisms.
| Yiu, Gloria; McCord, Alejandra; Wise, Alison et al. (2008) Pathways change in expression during replicative aging in Saccharomyces cerevisiae. J Gerontol A Biol Sci Med Sci 63:21-34 |
| Bradford, William D; Cahoon, Laty; Freel, Sara R et al. (2005) An inexpensive gel electrophoresis-based polymerase chain reaction method for quantifying mRNA levels. Cell Biol Educ 4:157-68 |
