Daf-2

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title: "Daf-2" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["caenorhabditis-elegans-genes", "aging-related-genes"] description: "Protein-coding gene in the species Caenorhabditis elegans" topic_path: "general/caenorhabditis-elegans-genes" source: "https://en.wikipedia.org/wiki/Daf-2" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Caenorhabditis elegans ::

::data[format=table title="Infobox nonhuman protein"]

Field	Value
Name	abnormal dauer formation protein 2
Organism	Caenorhabditis elegans
TaxID	6239
Symbol	daf-2
EntrezGene	175410
RefSeqmRNA	NM_065249.5
RefSeqProtein	NP_497650.4
UniProt	Q968Y9
Chromosome	III
EntrezChromosome	NC_003281.10
GenLoc_start	2994514
GenLoc_end	3028800
::

| Name = abnormal dauer formation protein 2 | image = | width = | caption = | Organism = Caenorhabditis elegans | TaxID = 6239 | Symbol = daf-2 | AltSymbols = | EntrezGene = 175410 | HomoloGene = | PDB = | RefSeqmRNA = NM_065249.5 | RefSeqProtein = NP_497650.4 | UniProt = Q968Y9 | Chromosome = III | EntrezChromosome = NC_003281.10 | GenLoc_start = 2994514 | GenLoc_end = 3028800 The DAF-2 gene encodes for the insulin-like growth factor 1 (IGF-1) receptor in the worm Caenorhabditis elegans. DAF-2 is part of the first metabolic pathway discovered to regulate the rate of aging. DAF-2 is also known to regulate reproductive development, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and resistance to bacterial pathogens. Mutations in DAF-2 and also Age-1 have been shown by Cynthia Kenyon to double the lifespan of the worms. In a 2007 episode of WNYC’s Radiolab, Kenyon called DAF-2 "the grim reaper gene.”

Long-lived mutants

Long-lived DAF-2 C. elegans mutants are resistant to the oxidizing agent paraquat and to UV light. DAF-2 mutants also have a higher DNA repair capability than wild-type C. elegans. Knockdown of the nucleotide excision repair gene Xpa-1 increases sensitivity to UV and reduces the life span of the long-lived mutants. These findings support the hypothesis that DNA damage has a significant role in the aging process.

IGF-1 signal pathway

Insulin/IGF-1-like signaling is well-conserved evolutionarily across animal phyla, from single celled organisms to mammals. DAF-2 is the only member of the insulin receptor family in C. elegans but it corresponds, in form and function, to multiple pathways in humans. The protein predicted from DAF-2's sequence is 35% identical to the human insulin receptor, which regulates metabolism; 34% identical to the IGF-1 receptor, which regulates growth; and 33% identical to the human insulin receptor–related receptor. In C. elegans, the insulin/IGF-1/FOXO pathway is initiated by changes in IGF-1 levels which cause IGF-1 receptors to start a phosphorylation cascade that deactivates the FOXO transcription factor, DAF-16. When not phosphorylated, DAF-16 is active and present in the nucleus. DAF-16 is responsible for up-regulating transcription of about 100 genes that code for cell protecting products such as heat shock proteins and antioxidants. Genetic analysis reveals that the presence of functioning DAF-16 is required to produce the extended lifespan observed in DAF-2 knock-downs. By silencing DAF-16, activation of DAF-2 receptors can ultimately compromise a cell’s ability to mitigate harmful environmental conditions. In most eukaryotes, insulin activates DAF-2 signaling. However, both human insulin and insulin coded for by orthologous genes in C. elegans inhibit DAF-2 receptors in C. elegans.

Role in ''C. elegans'' developmental stages

Caenorhabditis elegans, which progresses through a series of larval stages into a final reproductive adult, may instead enter a less metabolically active dauer diapause stage if food scarcity or overcrowding occurs before reaching adulthood. Disabling DAF-2 arrests development in the dauer stage which increases longevity, delays senescence and prevents reproductive maturity.

Diet’s interaction with the IGF-1 pathway

Research into the interaction between diet and the insulin/IGF-1 pathway has shown sugar intake to be negatively correlated with DAF-16 activity and longevity. One study found that glucose ingestion reduced the rate of dauer formation and shortened the life-spans of DAF-2 knock-downs to resemble that of normal C. elegans, suggesting that DAF-16 mediated gene expression associated with longevity is suppressed by glucose ingestion. Wild type C. elegans fed a diet that included 2% glucose showed reduced Daf-16 activity and lifespan was shortened by 20% compared to worms fed on glucose-free media. These findings raise the possibility that a low-sugar diet might have beneficial effects on life span in higher organisms.

References

References

1. (January 2011). "The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing". Philos Trans R Soc Lond B Biol Sci.
2. (February 2006). "Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for pharmacological manipulation of lifespan". Aging Cell.
3. (December 1995). "The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans". Genetics.
4. (October 1998). "Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span". Cell.
5. Krulwich, R. (Performer) (2007, June 14). Mortality. Radiolab. [Audio podcast]. Retrieved from http://www.radiolab.org/2007/jun/14/
6. (March 2008). "Longevity and resistance to stress correlate with DNA repair capacity in Caenorhabditis elegans". Nucleic Acids Research.
7. (July 2003). "Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans". Nature.
8. (August 1997). "daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans". Science.
9. (February 2005). "The plasticity of aging: insights from long-lived mutants". Cell.
10. Hu, 2007 Hu, P.J. (2007). Dauer. In WormBook, The C. elegans Research Community, ed. 10.1895/wormbook.1.144.1, http://www.wormbook.org.
11. (March 2001). "Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family". Genes & Development.
12. (November 2009). "Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression". Cell Metabolism.

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