Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92 Wu Cheng Road, Taiyuan, 030006, People's Republic of China.
College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, 030006, People's Republic of China.
Mol Genet Genomics. 2019 Dec;294(6):1463-1475. doi: 10.1007/s00438-019-01589-1. Epub 2019 Jul 20.
The pursuit of longevity has been the goal of humanity since ancient times. Genetic alterations have been demonstrated to affect lifespan. As increasing numbers of pro-longevity genes and anti-longevity genes have been discovered in Drosophila, screening for functionally important genes among the large number of genes has become difficult. The aim of the present study was to explore critical genes and pathways affecting longevity in Drosophila melanogaster. In this study, 168 genes associated with longevity in D. melanogaster were collected from the Human Ageing Genomic Resources (HAGR) database. Network clustering analysis, network topological analysis, and pathway analysis were integrated to identify key genes and pathways. Quantitative real-time PCR (qRT-PCR) was applied to verify the expression of genes in representative pathways and of predicted genes derived from the gene-gene sub-network. Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway. Moreover, the results revealed that six key genes in representative pathways, including Cat, Ry, S6k, Sod, Tor, and Tsc1, and the predicted genes Jra, Kay, and Rheb exhibited significant expression changes in ageing D. melanogaster strain w compared to young ones. Overall, our results revealed that six pathways and six key genes might play pivotal roles in regulating longevity, and three interacting genes might be implicated in longevity. The results will not only provide new insight into the mechanisms of longevity, but also provide novel ideas for network-based approaches for longevity-related research.
自古以来，追求长寿一直是人类的目标。遗传改变已被证明会影响寿命。随着越来越多的延长寿命基因和抗长寿基因在果蝇中被发现，在大量基因中筛选功能重要的基因变得困难。本研究旨在探索影响黑腹果蝇寿命的关键基因和途径。在这项研究中，从人类衰老基因组资源（HAGR）数据库中收集了与黑腹果蝇寿命相关的 168 个基因。整合网络聚类分析、网络拓扑分析和途径分析，以鉴定关键基因和途径。应用定量实时 PCR（qRT-PCR）验证代表性途径中基因的表达以及基因-基因子网中预测基因的表达。我们的结果表明，六个关键途径可能与长寿有关，包括长寿调节途径、过氧化物酶体途径、mTOR 信号通路、FOXO 信号通路、糖尿病并发症的 AGE-RAGE 信号通路和 TGF-β信号通路。此外，结果表明，代表性途径中的六个关键基因，包括 Cat、Ry、S6k、Sod、Tor 和 Tsc1，以及预测的基因 Jra、Kay 和 Rheb，在衰老的 D. melanogaster 菌株 w 中与年轻菌株相比表现出显著的表达变化。总体而言，我们的结果表明，六个途径和六个关键基因可能在调节寿命方面发挥关键作用，三个相互作用的基因可能与寿命有关。这些结果不仅将为长寿机制提供新的见解，也为基于网络的长寿相关研究提供了新的思路。
