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

Authors
  • Zečić, Aleksandra
  • Braeckman, Bart P.
Type
Published Article
Journal
Cells
Publisher
MDPI AG
Publication Date
Jan 02, 2020
Volume
9
Issue
1
Identifiers
DOI: 10.3390/cells9010109
PMID: 31906434
PMCID: PMC7017163
Source
PubMed Central
Keywords
License
Green

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.

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