ahr-1;mekk-3

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Genetic mutants with ahr-1, mekk-3 alterations

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

Temperature °C
20
Lifespan (days)
20.96
Lifespan change (compared to wild type)
19.91%
Phenotype
mekk-3 RNAi failed to extend lifespan in ahr-1(ia3) to the same extent as in WT worms.
Lifespan comparisons
Double mutant ahr-1(ia3);mekk-3(RNAi) has a lifespan of 20.96 days, while single mutant mekk-3(RNAi) has a lifespan of 27.98 days, single mutant ahr-1(ia3) has a lifespan of 18.43 days and wild type has a lifespan of 17.48 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Chamoli M et al., 2014, A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. Aging Cell. 13(4):641-55 24655420 Click here to select all mutants from this PubMed ID in the graph
Abstract
Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful.

Temperature °C
20
Lifespan (days)
15.33
Lifespan change (compared to wild type)
-12.35%
Phenotype
mekk-3 RNAi failed to extend lifespan in ahr-1(ia3) to the same extent as in WT worms.
Lifespan comparisons
Double mutant ahr-1(ia3);mekk-3(RNAi) has a lifespan of 15.33 days, while single mutant mekk-3(RNAi) has a lifespan of 30.29 days, single mutant ahr-1(ia3) has a lifespan of 17.1 days and wild type has a lifespan of 17.49 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Chamoli M et al., 2014, A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. Aging Cell. 13(4):641-55 24655420 Click here to select all mutants from this PubMed ID in the graph
Abstract
Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful.

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

Temperature °C
20
Lifespan (days)
14.92
Lifespan change (compared to wild type)
-14.65%
Phenotype
mekk-3 RNAi failed to extend lifespan in ahr-1(ju145) to the same extent as in WT worms.
Lifespan comparisons
Double mutant ahr-1(ju145);mekk-3(RNAi) has a lifespan of 14.92 days, while single mutant mekk-3(RNAi) has a lifespan of 27.98 days, single mutant ahr-1(ju145) has a lifespan of 16.16 days and wild type has a lifespan of 17.48 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Chamoli M et al., 2014, A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. Aging Cell. 13(4):641-55 24655420 Click here to select all mutants from this PubMed ID in the graph
Abstract
Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful.

Temperature °C
20
Lifespan (days)
19.24
Lifespan change (compared to wild type)
10.01%
Phenotype
mekk-3 RNAi failed to extend lifespan in ahr-1(ju145) to the same extent as in WT worms.
Lifespan comparisons
Double mutant ahr-1(ju145);mekk-3(RNAi) has a lifespan of 19.24 days, while single mutant mekk-3(RNAi) has a lifespan of 30.29 days, single mutant ahr-1(ju145) has a lifespan of 18.14 days and wild type has a lifespan of 17.49 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Chamoli M et al., 2014, A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. Aging Cell. 13(4):641-55 24655420 Click here to select all mutants from this PubMed ID in the graph
Abstract
Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful.

Search genes: ahr-1 mekk-3

Entrez ID
Symbol
GenAge
Wormbase ID

172788
ahr-1
View on GenAge (ahr-1)
WBGene00000096

Aryl hydrocarbon receptor protein 1

Locus: CELE_C41G7.5

Wormbase description: ahr-1 encodes an aryl hydrocarbon receptor (ligand-activated basic helix-loop-helix transcription factor) ortholog that biochemically resembles its vertebrate relatives (OMIM:600253) which mediate the carcinogenic and teratogenic effects of environmental toxins; AHR-1 activity is required for specification of RMEL and RMER GABAergic neuron cell fate and negative regulation of spontaneous movement; AHR-1 binds HSP90 tightly, and forms a dimer with AHA-1 that binds DNA fragments containing the mammalian xenobiotic response element; AHR-1 is expressed in neurons.

Symbol
GenAge

mekk-3
View on GenAge (mekk-3)

No gene information for mekk-3

Orthologs of ahr-1;mekk-3 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of ahr-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	dysf
Mus musculus	Ahr

Orthologs of mekk-3 in SynergyAge

Show in SynergyAge
Species	Gene