Identification of genes involved in longevity of insulin/Igf mutants

Abstract

The insulin/IGF´s pathway is conserved through evolution in all metazoans including C. elegans. Similarly to other animals, in C. elegans reduction of the activity of the insulin homologue pathway by mean of mutations in the insulin receptor homologue daf-2 gene or the PI3K age-1 gene generates a severe increase of longevity. This phenotype can be suppressed by the null mutation of the transcription factor DAF-16 (homologous to mammals FOXO). The objective of this work is to find C. elegans genes orthologous to human genes whose silencing allows decrease longevity. To this end we have generated an RNAi library containing 6.300 C. elegans genes which are considered orthologous to humans. This tool will allow us to carry out a screening to identify conserved genes that negatively regulate the longevity of the mutants as also it will be useful for other type of screenings. We performing the screening in two steps, first we are searching for suppressors of the reduced fertility by RNAi of mutants affected in the insulin pathway, this phenotype is easier to score than longevity. We then will test the suppression of longevity only with those genes that by RNAi suppress infertility.