Authors: Shaw WM; Luo S; Landis J; Ashraf J; Murphy CT
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.Keywords: Animals; Caenorhabditis elegans/growth & development/*physiology; Insulin/*physiology; Insulin-Like Growth Factor I/physiology; Longevity/*physiology; Signal Transduction/*physiology; Transforming Growth Factor beta/*physiology
Journal: Current biology : CB
Date: Sept. 29, 2007
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Shaw WM, Luo S, Landis J, Ashraf J, Murphy CT (2007) The C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling. Current biology : CB 17: 1635-45.