ArticleAging cell2014
A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans.
Article in Aging cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Intestinal lipid metabolism controls molecular and behavioral immunity through NHR-68 and gut-brain signaling in Caenorhabditis elegans.PLoS biology · 2026Article
- The TWK-26/KCNK3 potassium channel and FLR-4 protein kinase coordinate nutrient absorption in the C. elegans intestine.Genetics · 2026Article
- Mild mitochondrial impairment activates overlapping longevity pathways converging on the flavin-containing monooxygenase FMO-2.Frontiers in aging · 2026Article
- Unraveling the functional dynamics of Caenorhabditis elegans stress-responsive omega class GST-44.The FEBS journal · 2025Article
- LIN-39 is a neuron-specific developmental determinant of longevity in Caenorhabditis elegans with reduced insulin signaling.Nature communications · 2025Article
- Targeting farnesoid X receptor as aging intervention therapy.Acta pharmaceutica Sinica. B · 2025Article
- Activation of Nuclear Receptor CAR: A Pathway to Delay Aging through Enhanced Capacity for Xenobiotic Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 27-Hydroxymangiferolic Acid Extends Lifespan and Improves Neurodegeneration inMolecules (Basel, Switzerland) · 2025Article
- Kinome-wide RNAi screening inJournal of biosciences · 2025Article
- Calcineurin inhibition enhanceseLife · 2024Article
- Isotschimgine promotes lifespan, healthspan and neuroprotection of Caenorhabditis elegans via the activation of nuclear hormone receptors.Biogerontology · 2024Article
- Article
- Opposing action of the FLR-2 glycoprotein hormone and DRL-1/FLR-4 MAP kinases balance p38-mediated growth and lipid homeostasis in C. elegans.PLoS biology · 2023Article
- Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions.Nature communications · 2023Article
- ThemicroPublication biology · 2023Article
- Nuclear hormone receptor NHR-49 is an essential regulator of stress resilience and healthy aging inFrontiers in physiology · 2023Review
- The Aryl Hydrocarbon Receptor, Epigenetics and the Aging Process.The journal of nutrition, health & aging · 2023Article
- MEKK-3 Acts Cooperatively with NSY-1 in SKN-1-Dependent Manner against Oxidative Stress and Aging inBiology · 2022Article
- miR-181b regulates vascular endothelial aging by modulating an MAP3K3 signaling pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Remofuscin induces xenobiotic detoxification via a lysosome-to-nucleus signaling pathway to extend the Caenorhabditis elegans lifespan.Scientific reports · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.