The C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling.

TitleThe C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling.
Publication TypeJournal Article
Year of Publication2007
AuthorsShaw WM, Luo S, Landis J, Ashraf J, Murphy CT
JournalCurr Biol
Date Published2007 Oct 09
KeywordsAnimals, 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 JournalCurr. Biol.
Full Text
PubMed ID17900898
PubMed Central IDPMC3124252
Grant ListDP2 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