Insilico Identification of Genes and Molecular Pathways during Aging in Drosophila Brain

Arpita Parakh, D. Begde, N. Dhingra, D. Sinha
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Abstract

The regulation of gene expression in brain vicissitudes during aging is still not much known and explored. Differential gene expression and regulation is a key factor involved to identify the important landmarks within the brain transcriptome to study neuronal aging. Recently, transcriptomic studies are highly explored to understand and depict diseased versus normal as next generation sequencing enables to capture the complete biological context to the entire genome. Study of gene expression during aging compared to young flies provides a signature and scenario of gene expression and regulation during aging. In this study, we took advantage of NGS raw data of young and old flies head from SRA database of NCBI and decrypted the gene expression regulation during normal aging in drosophila model. We identified 350 genes with significant differential expression between young and old flies having 0.01% FDR. Various pathways in context to identified genes which are involved in aging include autophagy i.e. cell death and apoptosis, proteolysis, oxidative stress, declination grey and white matter and neurotransmitter levels, mitochondrial discrepancy, electron transport chain, sugar degradation pathways, activation of transcription factors involved in epigenetic changes, regulators involved in negative and positive regulation WNT signaling pathways, G protein coupled receptor etc. as all these factors contribute to neurodegeneration and possibly dementia in normal aging. So, to find the specific genes and regulators which are differentially expressed in normal aging, we investigate brain transcriptome of normal aging flies compared to young flies which offer a repertoire of genes, regulators and factors involved in network of neurodegeneration to establish direct correlation between aging and dementia. We also identified the pathways which are involved in aging and corresponding gene regulation in these pathways in aging flies brain. It is found that there are some common pathways whose genes and regulators are highly differentially regulated in both aging and dementia.
果蝇大脑衰老过程中基因和分子途径的计算机鉴定
基因表达在衰老过程中对大脑变化的调控尚不清楚。差异基因的表达和调控是确定脑转录组内重要标志以研究神经元衰老的关键因素。最近,转录组学研究被高度探索,以了解和描述患病与正常,因为下一代测序能够捕获整个基因组的完整生物学背景。衰老过程中基因表达的研究与年轻果蝇的比较提供了衰老过程中基因表达和调控的特征和场景。在本研究中,我们利用NCBI SRA数据库中年轻和年老果蝇头部的NGS原始数据,解密果蝇模型正常衰老过程中的基因表达调控。我们鉴定出350个基因在FDR为0.01%的年轻和年老果蝇之间有显著差异表达。与衰老有关的基因的各种途径包括自噬,即细胞死亡和凋亡,蛋白质水解,氧化应激,灰质和白质和神经递质水平下降,线粒体差异,电子传递链,糖降解途径,参与表观遗传变化的转录因子的激活,参与负调控和正调控的WNT信号通路,G蛋白偶联受体等,因为所有这些因素都有助于正常衰老中的神经变性和可能的痴呆。因此,为了找到在正常衰老过程中差异表达的特定基因和调控因子,我们研究了正常衰老果蝇与年轻果蝇的脑转录组,提供了一系列参与神经退行性网络的基因、调控因子和因子,以建立衰老与痴呆之间的直接关系。我们还确定了衰老果蝇大脑中参与衰老的途径以及这些途径中相应的基因调控。研究发现,在衰老和痴呆过程中,存在一些共同的通路,其基因和调控因子受到高度差异的调控。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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