SGK-1, the only C. elegans homolog of mammalian Serum- and Glucocorticoid-inducible Kinase, is an AGC kinase whose paralogs include two well-known kinases AKT-1 and AKT-2 in the insulin/IGF-1 signaling (IIS) pathway. Whether SGK-1 acts like AKT-1 and AKT-2 to regulate lifespan of C. elegans is controversial. Here we present experimental evidences to show that SGK-1 acts downstream of TORC1 (Target Of Rapamycin Complex 1), but not downstream of the IIS pathway, to regulate lifespan in C. elegans. Arguing against SGK-1 being functionally similar to AKT-1/2: 1. Multiple extensively backcrossed null alleles of
sgk-1 all shortened the lifespan of wild-type worms, which was opposite to the loss-of-function (lf) phenotypes of
akt-1 and
akt-2 in comparison, independent
sgk-1(gf) mutants lived slightly longer than the wild type. 2. Recombinant His-tagged DAF-16 was phosphorylated by immunoprecipitated AKT-2::GFP, but not SGK-1::GFP. 3. By IP-MS analysis, we found that SGK-1::GFP was associated with RSKS-1, the C. elegans S6 kinase and a component of the TORC1 signaling pathway. Verifying this finding, GST-SGK-1, but not GST pulled down RSKS-1::GFP (but not GFP alone) from worm lysates. 4. Null alleles of
sgk-1 suppressed the longevity phenotype induced by
eat-2(lf), rapamycin (inhibitor of TOR),
let-363 (TOR) RNAi,
raga-1 RNAi,
rsks-1(null), and AAK-2(1-321)::GFP overexpression, suggesting that TORC1 signaling limits lifespan by inhibiting SGK-1, at least in part. 5. Consistent with the reported finding that
rsks-1(null) greatly enhances the
daf-2 longevity,
sgk-1(gf) also further extends the lifespan of
daf-2(
e1370) worms. This result strengthens the idea that there is synergistic interaction between TORC1 and IIS signaling in lifespan regulation.