flr-4;nsy-1

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Genetic mutants with flr-4, nsy-1 alterations

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

Temperature °C
20
Diet
OP50; HT118
Lifespan (days)
15.02
Lifespan change (compared to wild type)
-13.03%
Phenotype
We found that increased life span on flr-4 RNAi is suppressed when nsy-1(ag3) in the p38 MAPK pathway is mutated.
Lifespan comparisons
Double mutant flr-4(RNAi);nsy-1(ag3) has a lifespan of 15.02 days, while single mutant flr-4(RNAi) has a lifespan of 25.45 days, single mutant nsy-1(ag3) has a lifespan of 14.96 days and wild type has a lifespan of 17.27 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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.

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

Temperature °C
20
Diet
OP50; HT119
Lifespan (days)
18.43
Lifespan change (compared to wild type)
6.72%
Phenotype
We found that increased life span on flr-4 RNAi is suppressed when nsy-1(ok593) in the p38 MAPK pathway is mutated.
Lifespan comparisons
Double mutant flr-4(RNAi);nsy-1(ok593) has a lifespan of 18.43 days, while single mutant flr-4(RNAi) has a lifespan of 25.45 days, single mutant nsy-1(ok593) has a lifespan of 17.36 days and wild type has a lifespan of 17.27 days.
Type of interaction
See methods
Dependent
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: flr-4 nsy-1

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.

Entrez ID
Symbol
GenAge
Wormbase ID

24104671
nsy-1
View on GenAge (nsy-1)
WBGene00003822

Mitogen-activated protein kinase kinase kinase nsy-1;Neuronal SYmmetry

Locus: CELE_F59A6.1

Wormbase description: nsy-1 encodes a MAP kinase kinase kinase (MAP3K) that is orthologous to the mammalian apoptosis signal-regulating kinase (ASK) family of protein kinases; nsy-1 activity is required for chemotaxis, egg laying, pathogen response, and response to anoxia; NSY-1 activity is activated by the calmodulin kinase UNC-43, and is required for lateral signalling that leads to asymmetric olfactory neuron fates; NSY-1 interacts with SEK-1, and is expressed in the intestine, hypodermis, rectal gland cells, and neurons.

Orthologs of flr-4;nsy-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of flr-4 in SynergyAge

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Species	Gene

Orthologs of nsy-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Ask1
Mus musculus	Map3k15
Mus musculus	Map3k5