UCSF

In both C. elegans and Drosophila, removing germline stem cells increases lifespan. In C. elegans, this lifespan extension requires the DAF-16/FOXO transcription factor and the DAF-12 nuclear hormone receptor, and the role of DAF-16/FOXO in this process may also be shared in flies. To better understand the regulatory relationships between

DAF-16 and DAF-12, we used microarray analysis to identify downstream genes. We found that these two transcription factors regulate distinct but overlapping sets of genes in response to loss of the germline. In addition, we identified several new genes that are required for loss of the germline to increase lifespan in C. elegans. One, phi-62, encodes

a conserved, predicted RNA binding protein. PHI-62 influences DAF-16-dependent transcription, possibly by collaborating with TCER-1, a putative transcription-elongation factor, and FTT-2, a 14-3-3- protein known to bind DAF-16. Three other genes encode proteins involved in lipid metabolism; one is a triacylglycerol lipase, and another is an

acyl CoA reductase. These genes do not affect bulk fat storage levels, but rather may influence production of a lifespan-extending signal or metabolite.