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Curr Biol. 2007 Oct 9;17(19):1635-45. Epub 2007 Sep 27.

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

Author information

1
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.

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.

PMID:
17900898
PMCID:
PMC3124252
DOI:
10.1016/j.cub.2007.08.058
[Indexed for MEDLINE]
Free PMC Article

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