|Title||The C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling.|
|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Shaw WM, Luo S, Landis J, Ashraf J, Murphy CT|
|Date Published||2007 Oct 09|
|Keywords||Animals, Caenorhabditis elegans, Insulin, Insulin-Like Growth Factor I, Longevity, Signal Transduction, Transforming Growth Factor beta|
BACKGROUND: Previous genetic evidence suggested that the C. elegans TGF-beta Dauer pathway is responsible solely for the regulation of dauer formation, with no role in longevity regulation, whereas the insulin/IGF-1 signaling (IIS) pathway regulates both dauer formation and longevity.
RESULTS: We have uncovered a significant longevity-regulating activity by the TGF-beta Dauer pathway that is masked by an egg-laying (Egl) phenotype; mutants in the pathway display up to 2-fold increases in life span. The expression profiles of adult TGF-beta mutants overlap significantly with IIS pathway profiles: Adult TGF-beta mutants regulate the transcription of many DAF-16-regulated genes, including genes that regulate life span, the two pathways share enriched Gene Ontology categories, and a motif previously associated with DAF-16-regulated transcription (the DAE, or DAF-16-associated element) is overrepresented in the promoters of TGF-beta regulated genes. The TGF-beta Dauer pathway's regulation of longevity appears to be mediated at least in part through insulin interactions with the IIS pathway and the regulation of DAF-16 localization.
CONCLUSIONS: Together, our results suggest there are TGF-beta-specific downstream targets and functions, but that the TGF-beta and IIS pathways might be more tightly linked in the regulation of longevity than has been previously appreciated.
|Alternate Journal||Curr. Biol.|
|PubMed Central ID||PMC3124252|
|Grant List||DP2 OD004402 / OD / NIH HHS / United States |
DP2 OD004402-01 / OD / NIH HHS / United States
T32 HG003284 / HG / NHGRI NIH HHS / United States
T32 HG003284-07 / HG / NHGRI NIH HHS / United States