Direct and indirect transcriptional targets of DAF-16.

Several genes involved in the determination of life span have been identified by mutation in the free-living soil nematode Caenorhabditis elegans. One of the key pathways studied in the context of life span is the DAF-2 pathway. The daf-2 gene is homologous to the insulin and insulin-like growth factor 1 receptor families. A downstream gene, daf-16, encodes a protein that is homologous to the forkhead transcription factor. A study by McElwee, Bubb, and Thomas, published in the current issue of Aging Cell, used genome-scale gene expression analysis to search for genes that are differentially expressed between long-lived daf-2(e1370) and short-lived daf-16(m27);daf-2(e1370) animals. In doing so, they identified candidate direct and indirect targets of DAF-16. In this Perspective, I discuss the results of this study.