Overexpression of Fatty-Acid-β-Oxidation-Related Genes Extends the Lifespan of Drosophila melanogaster.
Authors: Lee SH; Lee SK; Paik D; Min KJ Year: 2012 Journal: Oxidative medicine and cellular longevity Abstract: A better understanding of the aging process is necessary to ensure that the healthcare needs of an aging population are met. With the trend toward increased human life expectancies, identification of candidate genes affecting the regulation of lifespan and its relationship to environmental factors is essential. Through misexpression screening of EP mutant lines, we previously isolated several genes extending lifespan when ubiquitously overexpressed, including the two genes encoding the fatty-acid-binding protein and dodecenoyl-CoA delta-isomerase involved in fatty-acid beta-oxidation, which is the main energy resource pathway in eukaryotic cells. In this study, we analyzed flies overexpressing the two main components of fatty-acid beta-oxidation, and found that overexpression of fatty-acid-beta-oxidation-related genes extended the Drosophila lifespan. Furthermore, we found that the ability of dietary restriction to extend lifespan was reduced by the overexpression of fatty-acid-beta-oxidation-related genes. Moreover, the overexpression of fatty-acid-beta-oxidation-related genes enhanced stress tolerance to oxidative and starvation stresses and activated the dFOXO signal, indicating translocation to the nucleus and transcriptional activation of the dFOXO target genes. Overall, the results of this study suggest that overexpression of fatty-acid-beta-oxidation-related genes extends lifespan in a dietary-restriction-related manner, and that the mechanism of this process may be related to FOXO activation. Reference
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Created on Nov. 7, 2012, 7:24 p.m.
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fatty-acid-oxidation-related genes
Corn meal-sugar-yeast (CSY) media (5.2% cornmeal, 11% sucrose, 2.4% yeast, 0.8% agar, and 0.2% methyl-4-hydroxybenzoate
yeast concentration: 2, 4, 8, 12, 16%
EP/+ control cohorts without the Gal4 driver exhibit a longer lifespan than the parental cohorts.
Reduction of yeast concentration in a SY diet from 2 to 16% increases the median lifespan by 31.4%
dFOXO is regulates by IIS/PI3K/Akt, JNK, AMPK, MST1, CBP, and Sirt1 [12, 32-36]. l(2)efl and 4E-BP are dFOXO target genes.
Mutants for the mitochondria trifunctional protein containing three kinds of enzyme activities associated with fatty-acid- β-oxidation exhibit a shortenend lifespan and decreased locomotion and fecundity [41].
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