Recent ageing studies have revealed a very surprising finding:  Ageing can be regulated.  Even more surprising is that many of the classic signaling pathways that have been exhaustively studied for many years are involved in the regulation of ageing.  Down regulation of the insulin/IGF-1 signaling (IIS) pathway can result in long-lived worms, flies, mice and possibly humans.  Mutations in insulin/insulin-like ligand receptors disrupt a downstream phosphorylation cascade resulting in the nuclear localization of a foxO forhead transcription factor, gene expression changes in hundreds to thousands of genes and long –lived animals.  Our main focus is to understand the mechanisms of foxO gene regulation in long-lived worms and to determine the extent of conversation of these mechanism across a wide range of species.