Cell-Nonautonomous Signaling of FOXO/DAF-16 to the Stem Cells of Caenorhabditis elegans

In caenorhabditis elegans (c. elegans),the promotion of longevity by the transcription factor daf-16 requires reduced insulin/igf receptor (iir) signaling or the ablation of the germline,although the reason for the negative impact of germ cells is unknown. foxo/daf-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. in contrast to its function as a germline tumor suppressor,we now provide evidence that somatic daf-16 in the presence of iir signaling can also result in tumorigenic activity,which counteracts robust lifespan extension. in contrast to the cell-autonomous iir signaling,which is required for larval germline proliferation,activation of daf-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. shc-1 adaptor protein and akt-1 kinase antagonize,whereas akt-2 and sgk-1 kinases promote,this cell-nonautonomous daf-16 function. our data suggest that a functional balance of daf-16 activities in different tissues determines longevity and reveals a novel,cell-nonautonomous role of foxo/daf-16 to affect stem cells. © 2012 qi et al.