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
Volume17
Issue19
Pagination1635-45
Date Published2007 Oct 09
ISSN0960-9822
KeywordsAnimals, Caenorhabditis elegans, Insulin, Insulin-Like Growth Factor I, Longevity, Signal Transduction, Transforming Growth Factor beta
Abstract

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.

DOI10.1016/j.cub.2007.08.058
Alternate JournalCurr. Biol.
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