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Abstract
Mutations in genes functioning along the insulin-like signaling pathway in Caenorhabditis elegans extend life span up to three times the wild type phenotype. We sought to explain the mechanism behind this phenomenon by documenting gene expression in populations with these mutations via microarray analysis. The DAF-2 protein is analogous to the mammalian insulin receptor and functions at the head of the complex insulin-like signaling pathway. One branch of the pathway functions to antagonize DAF-16, a transcription factor which mediates hypomorph daf-2 phenotypes. These phenotypes include extended median lifespan, resistance to oxidative stress, increased longevity, thermotolerance, reduced fecundity, and delayed post-embryonic development. The first two of these are reported as O-GlcNAc dependent. O-GlcNAc is a common regulatory post-translational modification to proteins along this pathway. Microarrays were performed on six different mutant populations. Because in the daf-16; daf-2 mutants all six phenotypes are brought back to wild type and in the ogt-1; daf-2 mutant only the first two are, we were able to generate lists of candidate genes impacting each subset of phenotypes by microarray comparisons. This study is important to the genetic investigation of lifespan and carries implications for any species with the insulin signaling pathway.