DAF-16/FOXO, a Forkhead family transcription factor, controls a longevity-promoting transcriptome in response to reduced insulin/IGF-1 signaling (IIS) in C. elegans. It is intriguing how DAF-16/FOXO, by regulating the expression of many candidate anti-aging and pro-aging genes, controls a coordinated program of aging in different tissues. In our work to analyze cell autonomy for gene regulation by DAF-16/FOXO, we have demonstrated that "cross-talk" between different tissues that involves signal transmission is crucial to modulate gene expression and promote longevity in the whole animal. We are currently looking for signaling molecules that could serve as secondary