摘要：Twenty years ago it was discovered that loss of insulin/IGF-1-like signaling (IIS) ¨C such as occurs in daf-2(-) mutants ¨C dramatically extends longevity in the nematode C. elegans via the FOXO transcription factor DAF-16 [1-3]. Under favorable conditions, DAF-16 remains cytosolic and transcriptionally inactive[2-4]; under stress, it is driven into the nucleus, leading to both up-regulation and down-regulation of large sets of genes, referred to as Class I and II, respectively [5]. Identifying these genes and their functions is key to understanding the molecular and biochemical determinants of aging and longevity. While several studies have been performed to determine the genes regulated by DAF-16, agreement on the identity of targets has been limited to a relatively small number of top responders [6]. Moreover, recent results have made it clear that while DAF-16 is responsible for the activation of Class I genes through the DAF-16 binding element (DBE), it does not interact directly with the upstream promoter regions of Class II genes, leaving the down-regulation of the latter in IIS mutants unexplained
