daf-12;daf-2

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Genetic mutants with daf-12, daf-2 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Lifespan (days)
41.4
Phenotype
In the daf-2( e1370); daf- 12 ( m20) strain, the daf-12 mutation modifies the Daf-2 phenotype. Doublemutant animals constitutively arrested development as L2d or dauer-like larvae at 25.5. When the animals were raised at 15, then shifted to 25.5, the daf- 12( m20) mutation nearly doubled daf-2( e1370) adult longevity
Lifespan comparisons
Double mutant daf-12(m20);daf-2(e1370) has a lifespan of 41.4 days, while single mutant daf-2(e1370) has a lifespan of 26.7 days and wild type has a lifespan of 12 days.
Type of interaction
See methods
Partially known monotony. Positive epistasis
Citation
View abstract
Larsen PL et al., 1995, Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics. 139(4):1567-83 7789761 Click here to select all mutants from this PubMed ID in the graph
Abstract
The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determination of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan.

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Lifespan (days)
21.7
Lifespan comparisons
Double mutant daf-12(rh41rh411);daf-2(RNAi) has a lifespan of 21.7 days, while single mutant daf-12(rh41rh411) has a lifespan of 15.8 days.
Citation
View abstract
Hansen M et al., 2005, New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet. 1(1):119-28 16103914 Click here to select all mutants from this PubMed ID in the graph
Abstract
Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i) that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii) that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii) that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

Search genes: daf-12 daf-2

Entrez ID
Symbol
GenAge
Wormbase ID

181263
daf-12
View on GenAge (daf-12)
WBGene00000908

Nuclear hormone receptor family member daf-12

Locus: CELE_F11A1.3

Wormbase description: daf-12 encodes a member of the steroid hormone receptor superfamily that is homologous to human VITAMIN D RECEPTOR (VDR; OMIM:601769, mutated in vitamin D-resistant rickets); daf-12 affects dauer formation downstream of the TGF- and insulin signaling pathways, and affects gonad-dependent adult longevity together with DAF-16, chemosensory signal transduction, and distal tip cell migration and hypodermal and intestinal cell lineages during the L3 larval stage; DAF-12 is expressed in the nucleus and in most cells; daf-12 expression in lateral seam cells is negatively regulated by the let-7 miRNA.

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Orthologs of daf-12;daf-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hr96;InR
Mus musculus	InR;Hr96

Orthologs of daf-12 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hr96

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr