Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age.
Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age.
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DOI：
10.1371/journal.pone.0161143
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Dotti CG
中科院分区：
文献类型：
--
作者：
Laranjeira A;Schulz J;Dotti CG
人们普遍认为，在生物体中，衰老是一个多方面过程的结果，包括损害随着时间的推移逐渐积累，对功能和生存都有影响。老龄化的研究提出了几个挑战，从所涉及的不同机制到随着时间的推移受到影响的系统的巨大多样性。在目前的研究中，我们着手确定参与大脑功能随年龄下降的基因，并使用果蝇作为模型系统，以组织依赖的方式研究其相关性。在这里，我们报告了雌性野生型果蝇神经组织中脂肪酸β-氧化代谢过程相关基因的年龄依赖性上调。CG 10814、dHNF 4和脂质动员基因bmm和dAkh的下调在细胞和行为水平上挽救了随着年龄增长的脑功能衰退，而过度表达则损害了表现。我们的数据表明，随着年龄的增长，果蝇大脑中发生了代谢变化，脂肪酸的β-氧化过程经历了遗传功能获得。这一事件被证明是导致大脑功能随年龄增长而下降的主要原因之一。
In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. In the current study, we set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. Here we report the age-dependent upregulation of genes involved in the metabolic process of fatty acid β-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. Our data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of β-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age.