Ageing is a degenerative process that affects all multi cellular organisms including humans. Although the ageing process has been known since the human origin, the mechanism of how this happens and how is regulated is still unknown. The little we know about this process has been learned mainly thanks to the study and characterization of long-lived mutants of the nematode Caenorhabditis elegans. However the number of known loci is small and we think that it is essential to isolate new long-lived mutants for the complete understanding of the process.
Our work has focused on this idea. The search for long-lived mutants by their longevity phenotype requires a great effort and is time consuming. In order to avoid this problem, we positive selected for thermotolerant mutants (a phenotype associate with longevity) with the hope that some of the mutants were long lived. Using this protocol we have isolated a large collection of long-lived mutants some of which affect known genes and others represent novel genes.
Currently we are in the process of characterizing the mutants and identifying the genes affected. Up to now, we have identified the gene affected in the aap-1 mutant. This gene encodes the regulatory subunit of phosphoinositol 3-Kinase, a key enzyme in the insulin/IGF signal transduction pathway. This gene, together with other genes involved in the insulin/IGF signaling pathway previously identified by other groups, indicate that there is a hormonal regulation of ageing. Different mutants of this pathway in Drosophila and mice affect also longevity in a similar way, suggesting that the pathway is conserved through evolution.