Department of Biological Sciences, Inha University, 100 Inha-ro, Nam-gu, Incheon 402-751, Republic of Korea.
Oxid Med Cell Longev. 2012;2012:854502. doi: 10.1155/2012/854502. Epub 2012 Sep 11.
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 β-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 β-oxidation, and found that overexpression of fatty-acid-β-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-β-oxidation-related genes. Moreover, the overexpression of fatty-acid-β-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-β-oxidation-related genes extends lifespan in a dietary-restriction-related manner, and that the mechanism of this process may be related to FOXO activation.
更好地了解衰老过程对于确保满足老龄化人口的医疗保健需求至关重要。随着人类预期寿命延长的趋势，鉴定影响寿命调节及其与环境因素关系的候选基因至关重要。通过对 EP 突变系的异位表达筛选，我们之前分离到了几个当广泛过表达时可延长寿命的基因，包括编码参与脂肪酸 β-氧化的脂肪酸结合蛋白和十二烯酰-CoA Δ-异构酶的两个基因，脂肪酸 β-氧化是真核细胞的主要能量资源途径。在这项研究中，我们分析了过表达两种脂肪酸 β-氧化主要成分的果蝇，发现过表达脂肪酸 β-氧化相关基因可延长果蝇的寿命。此外，我们发现过表达脂肪酸 β-氧化相关基因会降低饮食限制延长寿命的能力。此外，过表达脂肪酸 β-氧化相关基因可增强对氧化和饥饿应激的耐受能力，并激活 dFOXO 信号，表明其向核内易位和转录激活 dFOXO 靶基因。总的来说，这项研究的结果表明，过表达脂肪酸 β-氧化相关基因以与饮食限制相关的方式延长寿命，而这一过程的机制可能与 FOXO 激活有关。
