The C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling.
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.
Shaw
Wendy M
WM
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Luo
Shijing
S
Landis
Jessica
J
Ashraf
Jasmine
J
Murphy
Coleen T
CT
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000502:physiology*; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008136:Longevity / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D007328:Insulin; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I