Aging Cell | |
A novel kinase regulates dietary restriction‐mediated longevity in Caenorhabditis elegans | |
Manish Chamoli1  Anupama Singh1  Yasir Malik1  | |
[1] Molecular Aging Laboratory, National Institute of Immunology, New Delhi, India | |
关键词: beta‐oxidation; Caenorhabditis elegans; dietary restriction; fat storage; lifespan; xenobiotic detoxification; | |
DOI : 10.1111/acel.12218 | |
来源: Wiley | |
【 摘 要 】
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.Summary
【 授权许可】
CC BY
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
【 预 览 】
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