| Citation | Chamoli M, Singh A, Malik Y, Mukhopadhyay A. A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. Aging Cell, 2014. |
| PubMed ID | 24655420 |
| Short Description | A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. GEO Record: GSE40252 Platform: GPL11346 Download gene-centric, log2 transformed data: WBPaper00045036.ce.mr.csv |
| # of Conditions | 4 |
Full Description
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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. Experimental Details: WBPaper00045036:control(RNAi)_rep1 WBPaper00045036:control(RNAi)_rep2 WBPaper00045036:drl-1(RNAi)_rep1 WBPaper00045036:drl-1(RNAi)_rep2. |
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