Dietary Supplements May Increase Longevity by Up-regulation of Daf-16/FoxO Gene
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An AMPK-FOXO Pathway Mediates Longevity Induced by a Novel Method of Dietary Restriction in C. elegans
BACKGROUND Dietary restriction (DR) is the most effective environmental intervention to extend lifespan in a wide range of species. However, the molecular mechanisms underlying the benefits of DR on longevity are still poorly characterized. AMP-activated protein kinase (AMPK) is activated by a decrease in energy levels, raising the possibility that AMPK might mediate lifespan extension by DR. ...
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FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an...
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The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity determinant in diverse organisms, however the molecular basis of how its transcriptional activity is regulated remains largely unknown. We report that the Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new longevity modulator and functions as a negative regulator of DAF-16. In C. elegans, hc...
متن کاملTranscriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan
BACKGROUND Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 ha...
متن کاملThe search for DAF-16/FOXO transcriptional targets: approaches and discoveries.
The insulin/IGF-1 receptor (IIR)/FOXO pathway is remarkably conserved in worms, flies, and mammals, and downregulation of signaling in this pathway has been shown to extend lifespan in all of these animals. FOXO-mediated transcription is required for the long lifespan of IIR mutants; thus, there is great interest in identifying FOXO target genes, as they may carry out the biochemical activities...
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