Cited by 189Genetics, Aging, and Longevity in Model OrganismsFOXO transcription factor regulationMetabolism, Diabetes, and Cancer

The search for DAF-16/FOXO transcriptional targets: Approaches and discoveries

Murphy, Coleen T.·2006·Experimental Gerontology

Abstract

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 that extend longevity. A number of approaches have been used to identify the transcriptional targets of FOXO. Thus far, the best data available on the components downstream of this pathway are from experiments involving the Caenorhabditis elegans FOXO transcription factor, DAF-16; some of these targets have been tested for their contributions to longevity, dauer formation, and fat storage. Here, I examine and compare the approaches used to identify DAF-16/FOXO targets, review the genes regulated by DAF-16, and discuss the processes that may be at work to extend lifespan in IIR mutants. Rather than upregulating every possible beneficial gene, DAF-16 appears to selectively upregulate genes that contribute to specific protective mechanisms, while simultaneously downregulating potentially deleterious genes. In addition to genes that carry out expected roles in stress protection, many previously unknown targets have been identified in these studies, suggesting that some mechanisms of lifespan extension still await discovery. These mechanisms may act cooperatively or cumulatively to increase longevity, and are likely to be at least partially conserved in higher organisms.

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Crossref · 10.1016/j.exger.2006.06.040

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  • Transcriptional targets of daf-16 include enzymes involved in metabolism and stress resistance.

    “Interestingly, the transcriptional targets of daf-16 include a number of enzymes that are involved in metabolism as well as stress resistance 91 .”

    From The common biology of cancer and ageing (2007) · cites this paper as [91]

  • Foxo3 controls expression of multiple genes involved in stress resistance and metabolism.

    “The closest mammalian orthologue of daf-16 is Foxo3, and there is evidence that this mammalian transcription factor also controls the expression of multiple genes involved in stress resistance and metabolism 91 .”

    From The common biology of cancer and ageing (2007) · cites this paper as [91]

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Authors
Murphy, C. T.
Affiliations
Princeton University (US)
Corresponding author
Murphy, Coleen T.
Venue
Experimental Gerontology
Publisher
Elsevier BV
Published
2006-10
Volume
41
Issue
10
Pages
910-921
ISSN
0531-5565 (ISSN-L)
OpenAlex
W1966040173
Cited by
189
References
70
Citations by year
2026: 2 · 2025: 6 · 2024: 9 · 2023: 3 · 2022: 10 · 2021: 12 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 16 · 2013: 13 · 2012: 20
FWCI
2.64
Type
journal article
Language
en
Open access
closed
Locations
  • Experimental Gerontology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
DAF-16, FOXO transcription factors, transcription factor target genes, lifespan extension, longevity, Caenorhabditis elegans, dauer formation, fat deposition, stress protection, gene expression regulation
MeSH terms
Aging, Animals, Insulin, Longevity, Models, Genetic, Receptor, Insulin, Transcription Factors, Transcription, Genetic, Signal Transduction, Caenorhabditis elegans, Genes, Helminth, Receptor, IGF Type 2, Gene Expression Regulation, Developmental, Caenorhabditis elegans Proteins, Forkhead Transcription Factors

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