ANNOTATION OF C. ELEGANS GENES ASSOCIATED WITH LONGEVITY USING SERIAL ANALYSIS OF GENE EXPRESSION (SAGE)

Abstract

We are studying the gene expression profiles of C. elegans daf-2 mutants. During the last decade there has been major progress on the genetics of life span through the study of mutants with extended longevity. In particular, mutations in two genes, daf-2 and age-1 (components of the insulin-like signaling pathway), resulted in significant (2-3 fold) extension of adult life span. Lund et al. (Current Biology 2002 12:1566-1573) identified a relatively small number of genes (<1% of genome), which change their expression with aging. To identify genes associated with the daf-2 phenotype, we are using SAGE to compare the transcriptional profiles of daf-2 and normal adults at various ages. To distinguish genes primarily associated with longevity from those involved in dauer larva formation and maintenance or genes associated with a general stress response, we are also profiling gene expression in young and old dauer larvae, starved and normal L1 larvae, and pheromone-induced L2d (pre-dauer) larvae. Currently, we are taking the following approaches: 1) searching for candidate genes affecting longevity that are differentially expressed in long-lived worms using both publicly available and in-house developed software with statistical tools for analyzing gene expression data, 2) global gene expression profiling with annotation of genes, specific to dauer larvae and daf-2 adults, and 3) validation of selected computationally-derived results by RNAi experiments.