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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
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 109;
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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