When the germ cell precursors of C. elegans are removed, the animals lifespan is increased approximately 60% (1). In response to germline removal, the FOXO transcription factor DAF-16 accumulates in nuclei in the intestine (2), where it functions to extend the lifespan of the animal (3). We identified another transcription factor,
gos-1, in a screen for additional genes required for loss of the germline to extend lifespan.
gos-1 plays an important role in longevity, because we find that overexpression of a GOS-1::GFP fusion protein extends the lifespan of wild-type animals.
gos-1 may regulate longevity in association with DAF-16, since
daf-16 is required for
gos-1 overexpression to extend lifespan, and
gos-1reduction-of-function prevents loss of the germline from up-regulating specific DAF-16 target genes. The expression of
gos-1 is regulated by signals from the reproductive system. When the germ cell precursors are removed using a laser microbeam or a
glp-1(ts) mutation, transcription of
gos-1 increases in the intestine. Previously, we found that the genes
kri-1, which encodes a putative adaptor protein expressed in the intestine, and
daf-9 and
daf-12, which encode components of a lipophilic-hormone signaling pathway (4,5), are required for DAF-16 to accumulate in intestinal nuclei following the removal of the germline (6). Unexpectedly, none of these genes is required for the up-regulation of
gos-1 expression following germline removal. Thus there must be a second, undefined, signaling pathway from the reproductive system to the intestine that is required for lifespan extension following germline removal.
gos-1 is not required for the longevity of insulin/IGF-1 receptor mutants, even though both germline-less animals and
daf-2 mutants require DAF-16 for their longevity. Thus GOS-1 may be part of a pathway that influences DAF-16 activity specifically in response to germline removal. 1. Hsin, H., and C. Kenyon. 1999, Nature 399:362. 2. Lin, K., H. Hsin, N. Libina, and C. Kenyon. 2001. Nature Genetics 28:139. 3. Libina, N., J. R. Berman, and C. Kenyon. 2003. Cell 115:489. 4. Antebi, A., W. H. Yeh, D. Tait, E. M. Hedgecock, and D. L. Riddle. 2000. Genes Dev 14:1512. 5. Gerisch, B., C. Weitzel, C. Kober-Eisermann, V. Rottiers, and A. Antebi. 2001. Dev Cell 1:841. 6. Berman, J. R., and C. Kenyon. 2006. Cell 124:1055.