Project description:Aneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality-control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age-associated phenotypes.
Project description:In this study, we used Saccharomyces cerevisiae to investigate the effects of GRX deletion on yeast chronological life span (CLS). Deletion of Grx1 or Grx2 shortened yeast CLS. Quantitative proteomics revealed that GRX deletion increased cellular ROS levels to activate Ras/PKA signal pathway. Our results provided new insights into mechanisms underlying aging process.
Project description:Yeast replicative aging is a process resembling replicative aging in mammalian cells. During aging, wild type haploid yeast cells enlarge, become sterile, and undergo nucleolar enlargement and fragmentation; we sought gene expression changes during the time of these phenotypic changes. Gene expression studied via microarrays and qPCR has shown reproducible, statistically significant changes in mRNA of genes at 12 and 18-20 generations. Our findings support previously described changes towards aerobic metabolism, decreased ribosome gene expression, and a partial Environmental Stress Response. Our novel findings include a pseudo-stationary phase, down-regulation of methylation-related metabolism, increased Nucleotide Excision Repair related mRNA, and a strong up-regulation of many of the regulatory subunits of protein phosphatase I (Glc7). These findings are correlated with aging changes in higher organisms as well as with the known involvement of protein phosphorylation states during yeast aging. J Gerontol, Jan, 2008, vol 63A, no. 1. Keywords: aging time course
Project description:Aneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality-control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age-associated phenotypes. These are all CGH arrays comparing DNA content between the indicated strain of interest and a wt control.