daf-2

Symbol: daf-2
Name: abnormal DAuer Formation 2
Alias: abnormal DAuer Formation DAF-2
Entrez gene ID: 175410
Ensembl gene ID: Y55D5A.5
Species: Worm (Taxid: 6239)

Functional description:
An insulin receptor-like protein which regulates metabolism, controls longevity and prevents developmental arrest at the dauer stage. Binding of INS family members may either stimulate, or antagonise, association of the receptor with downstream mediators such as pdk-1 and age-1. Required for the response to environmental stimuli such as food, pheromone, and temperature. Role in immune function and pathogen resistance. [UniProt]

Observation:

daf-2 mutants live more than twice as long as controls. daf-2(sa189) mutation extends mean and maximum lifespan by 133 and 129%, respectively, when shifted to 20 degree Celsius. The daf-2(e1370) mutation extends mean and maximum lifespan by 32 and 119%, respectively, when shifted to 25 degree Celsius and by 110 and 145%, respectively, at 20 degree Celsius. daf-2(sa189) mutation extends mean lifespan by 67% as well as maximum lifespan [8247153]. This lifespan extension requires the activity of daf-16 [8247153]. The lifespan extension of daf-2(e1370) mutants is cancelled out by daf-16(m26) mutation. daf-2 mutants still exhibit a long lifespan after ablation of the gonad and germ cells. [8247153]. daf-2(e1370) increases mean (95-118%) and maximum (165%) lifespan [18828672]. RNAi against daf-2 extends mean and maximum lifespan by 47 and 65% [12471266]. daf-2 mutation extends lifespan of wild-type and eat-2 mutants [9789046]. Long lifespan of daf-2 insulin receptor mutation is further extended by sDR. However, daf-2 mutation is not a null mutation, therefore it is still possible that part of sDR-induced increase in lifespan might depend on insulin receptor pathway [17900900]. DR by bacterial dilution extends lifespan of daf-2 mutants [17538612]. IF does not markedly extend lifespan of daf-2 mutants [19079239]. 2% glucose reduce fractions of animals that become dauers at 22.5 degree Celsius in daf-2 mutants. Glucose almost completely suppresses lifespan extension of daf-2 ligand binding domain and tyrosine kinase mutants back to wild-type levels [19883616]. daf-2 mutation increases average lifespan by 157%. Under AL daf-2 mutation increases lifespan by 30%. bDR increases lifespan by 65%. daf-2 mutation further increases lifespan under bDR by 40%. Resistance to oxidative stress is reduced daf-2 mutation [19924292]. daf-2 RNAi increases mean lifesapn by 89% [18828672]. daf-2(m577) mutation increases mean and maximum lifespan by 33 and 29%, respectively, while daf-2(e1370) mutation increases mean and maximum lifespan by 101 and 181%, respectively [16782295]. DR from eat-2(ad465) mutation has an addative effect on lifespan of daf-2(e1370) adults, but not on lifespan of daf-2(e1368) adults [18043747]. Mutation in daf-2 in combination with mutation of daf-12 results in nearly 300% increase in lifespan [7789761]. daf-2 mutants are dauer constitutive [7219552] and exhibit reduced brood size [9504918; 9725835]. daf-2 mutants synergize with germ line ablation for lifespan extension [10360574] and also exhibit synergy with clk-1 mutation for lifespan prolongation [8638122]. All the phenotypes of daf-2 mutants are suppressed by mutation of daf-16 [8247153; 8601482; 7789761; 9725835; 9504918]. Mutation of daf-2 increases expression of sod-3 [10428762]. daf-2(e1370) increases mean lifespan by 146% [23097426].

Reducing expression of daf-2 in the adult stage alone extends lifespan [12399591].



Interventions:
  • daf-2 RNAi +47 to +89% +65%
  • daf-2 mutation +32 to +146% +119 to +165%

  • Assays: Organismal Lifespan
    Mean: +32 to +146
    Maximum: +119 to +165

    Classification:
  • Gerontogene
  • Positive Gerontogene
  • DR-Essential


  • References:
  • 12471266: Rates of behavior and aging specified by mitochondrial function during development.
  • 8247153: A C. elegans mutant that lives twice as long as wild type.
  • 18828672: Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator.
  • 19079239: Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans.
  • 16782295: Increased lifespan in transgenic Caenorhabditis elegans overexpressing human alpha-synuclein.
  • 19924292: Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.
  • 19883616: Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression.
  • 18043747: DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.
  • 10360574: Signals from the reproductive system regulate the lifespan of C. elegans.
  • 10428762: The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans.
  • 17900900: An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans.
  • 17538612: Two neurons mediate diet-restriction-induced longevity in C. elegans.
  • 23097426: Post-developmental microRNA expression is required for normal physiology, and regulates aging in parallel to insulin/IGF-1 signaling in C. elegans.
  • 12399591: Timing requirements for insulin/IGF-1 signaling in C. elegans.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • IGF1R (9606)
  • IGF1R (9598)
  • IGF1R (9615)
  • IGF1R (9913)
  • Igf1r (10090)
  • Igf1r (10116)
  • IGF1R (9031)
  • igf1ra (7955)
  • igf1rb (7955)
  • InR (7227)
  • INR (7165)
  • daf-2 (6239)

  • Orthologs
  • Igf1r (10090)
  • NTRK3 (9544)
  • IGF1R (9606)
  • NTRK1 (9544)
  • Ntrk1 (10090)
  • Ntrk2 (10090)
  • Ntrk3 (10090)
  • Ntrk3 (10116)
  • NTRK2 (9606)
  • NTRK3 (9606)
  • InR (7227)
  • INSR (9606)
  • INSRR (9606)
  • Insr (10090)
  • IGF1R (9544)
  • Ntrk2 (10116)
  • Ntrk1 (10116)
  • LOC719974 (9544)
  • CG3837 (7227)
  • INSR (9544)
  • CG10702 (7227)
  • Insrr (10090)
  • Igf1r (10116)
  • Insrr (10116)
  • Insr (10116)
  • NTRK1 (9606)
  • INSRR (9544)
  • NTRK2 (9544)
  • Igf1r (10090)
  • NTRK3 (9544)
  • IGF1R (9606)
  • NTRK1 (9544)
  • Ntrk1 (10090)
  • Ntrk2 (10090)
  • Ntrk3 (10090)
  • Ntrk3 (10116)
  • NTRK2 (9606)
  • NTRK3 (9606)
  • InR (7227)
  • INSR (9606)
  • INSRR (9606)
  • Insr (10090)
  • IGF1R (9544)
  • Ntrk2 (10116)
  • Ntrk1 (10116)
  • LOC719974 (9544)
  • CG3837 (7227)
  • INSR (9544)
  • CG10702 (7227)
  • Insrr (10090)
  • Igf1r (10116)
  • Insrr (10116)
  • Insr (10116)
  • NTRK1 (9606)
  • INSRR (9544)
  • NTRK2 (9544)



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