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DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling

Laboratory of Aging Physiology and Molecular Evolution, Department of Biology, Ghent University, 9000 Ghent, Belgium
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Cells 2020, 9(1), 109; https://doi.org/10.3390/cells9010109
Received: 28 November 2019 / Revised: 30 December 2019 / Accepted: 31 December 2019 / Published: 2 January 2020
(This article belongs to the Special Issue The FoxO Transcription Factors and Metabolic Regulation)
DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in Caenorhabditis elegans, integrates signals from upstream pathways to elicit transcriptional changes in many genes involved in aging, development, stress, metabolism, and immunity. The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In C. elegans daf-2 mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood. This program includes elevated antioxidant defense and a metabolic shift toward accumulation of carbohydrates (i.e., trehalose and glycogen) and triglycerides, and activation of the glyoxylate shunt, which could allow fat-to-carbohydrate conversion. The longevity of daf-2 mutants seems to be partially supported by endogenous trehalose, a nonreducing disaccharide that mammals cannot synthesize, which points toward considerable differences in downstream mechanisms by which IIS regulates aging in distinct groups. View Full-Text
Keywords: DAF-16/FoxO; aging; longevity; metabolic shift; trehalose; glycogen; fat DAF-16/FoxO; aging; longevity; metabolic shift; trehalose; glycogen; fat
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Zečić, A.; Braeckman, B.P. DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling. Cells 2020, 9, 109.

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