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Review
. 2020 Jan 2;9(1):109.
doi: 10.3390/cells9010109.

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

Aleksandra Zečić  1 , Bart P Braeckman  1
Affiliations
Review

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

Aleksandra Zečić et al. Cells. .

Abstract

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.

Keywords: DAF-16/FoxO; aging; fat; glycogen; longevity; metabolic shift; trehalose.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Simplified graphic summary of the DAF-16-dependent metabolic remodeling in the Caenorhabditis elegans daf-2 mutant, with emphasis on the major carbon stores and their interconversion.
See this image and copyright information in PMC

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