daf-2;flr-4

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Genetic mutants with daf-2, flr-4 alterations

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

Temperature °C
20
Diet
OP50; HT129
Lifespan (days)
64.74
Lifespan change (compared to wild type)
238.42%
Phenotype
The life span of daf-2(e1370) was further increased when flr-4 was knocked down using RNAi.
Lifespan comparisons
Double mutant daf-2(e1370);flr-4(RNAi) has a lifespan of 64.74 days, while single mutant flr-4(RNAi) has a lifespan of 26.44 days, single mutant daf-2(e1370) has a lifespan of 41.36 days and wild type has a lifespan of 19.13 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Verma S et al., 2018, A novel gene-diet pair modulates C. elegans aging. PLoS Genet. 14(8):e1007608 30125273 Click here to select all mutants from this PubMed ID in the graph
Abstract
Diet profoundly affects metabolism and incidences of age-related diseases. Animals adapt their physiology to different food-types, modulating complex life-history traits like aging. The molecular mechanisms linking adaptive capacity to diet with aging are less known. We identify FLR-4 kinase as a novel modulator of aging in C. elegans, depending on bacterial diet. FLR-4 functions to prevent differential activation of the p38MAPK pathway in response to diverse food-types, thereby maintaining normal life span. In a kinase-dead flr-4 mutant, E. coli HT115 (K12 strain), but not the standard diet OP50 (B strain), is able to activate p38MAPK, elevate expression of cytoprotective genes through the nuclear hormone receptor NHR-8 and enhance life span. Interestingly, flr-4 and dietary restriction utilize similar pathways for longevity assurance, suggesting cross-talks between cellular modules that respond to diet quality and quantity. Together, our study discovers a new C. elegans gene-diet pair that controls the plasticity of aging.

Search genes: daf-2 flr-4

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.

Entrez ID
Symbol
GenAge
Wormbase ID

181604
flr-4
View on GenAge (flr-4)
WBGene00001468

Serine/threonine-protein kinase flr-4

Locus: CELE_F09B12.6

Wormbase description: flr-4 encodes a predicted Ser/Thr protein kinase that affects sensitivity to fluoride ion, growth, defecation cycle periods, dauer formation; expressed in the intestine, the AUA neurons, the pharyngeal isthmus, and in the excretory canal in larval stages.

Orthologs of daf-2;flr-4 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-2 in SynergyAge

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Species	Gene
Drosophila melanogaster	InR

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

Orthologs of flr-4 in SynergyAge

Show in SynergyAge
Species	Gene

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.