Decreased functioning of the signaling pathway triggered by peptide hormones of the insulin family leads to more efficient use of food, increased resistance to stress, and longer lives. To identify genes that are the ultimate targets of this pathway responsible for these effects, Lee et al. looked for binding sites for the transcription factor DAF-16/FOXO that are conserved in the Drosophila and Caenorhabditis genomes. They then identified genes regulated by the insulin family that influenced metabolism and longevity, including those for pantothenate kinase, 4-hydroxyphenylpyuruvate dioxygenase, an ABC transporter, and a protein similar to retinoblastoma binding protein 2. S. S. Lee, S. Kennedy, A. C. Tolonen, G. Ruvkun, DAF-16 target genes that control C. elegans life-span and metabolism. Science 300 , 644-647 (2003). [Abstract] [Full Text]