Centre for Computational Natural Sciences and Bioinformatics, IIIT, Hyderabad, 500032, India.
Sci Rep. 2023 Mar 21;13(1):4632. doi: 10.1038/s41598-023-31315-2.
The liver plays a vital role in maintaining whole-body metabolic homeostasis, compound detoxification and has the unique ability to regenerate itself post-injury. Ageing leads to functional impairment of the liver and predisposes the liver to non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Mapping the molecular changes of the liver with ageing may help to understand the crosstalk of ageing with different liver diseases. A systems-level analysis of the ageing-induced liver changes and its crosstalk with liver-associated conditions is lacking. In the present study, we performed network-level analyses of the ageing liver using mouse transcriptomic data and a protein-protein interaction (PPI) network. A sample-wise analysis using network entropy measure was performed, which showed an increasing trend with ageing and helped to identify ageing genes based on local entropy changes. To gain further insights, we also integrated the differentially expressed genes (DEGs) between young and different age groups with the PPI network and identified core modules and nodes associated with ageing. Finally, we computed the network proximity of the ageing network with different networks of liver diseases and regeneration to quantify the effect of ageing. Our analysis revealed the complex interplay of immune, cancer signalling, and metabolic genes in the ageing liver. We found significant network proximities between ageing and NAFLD, HCC, liver damage conditions, and the early phase of liver regeneration with common nodes including NLRP12, TRP53, GSK3B, CTNNB1, MAT1 and FASN. Overall, our study maps the network-level changes of ageing and their interconnections with the physiology and pathology of the liver.
肝脏在维持全身代谢稳态、化合物解毒方面起着至关重要的作用，并且具有损伤后自我再生的独特能力。随着年龄的增长，肝脏功能会受损，使肝脏易患非酒精性脂肪性肝病（NAFLD）和肝细胞癌（HCC）。对肝脏衰老过程中的分子变化进行绘图，可能有助于理解衰老与不同肝脏疾病的相互作用。目前缺乏对衰老引起的肝脏变化及其与肝脏相关疾病相互作用的系统水平分析。在本研究中，我们使用小鼠转录组数据和蛋白质-蛋白质相互作用（PPI）网络对衰老肝脏进行了网络水平分析。我们对样本进行了网络熵测度分析，结果显示随着年龄的增长呈上升趋势，有助于根据局部熵变化识别衰老基因。为了获得更深入的见解，我们还将年轻组和不同年龄组之间的差异表达基因（DEGs）与 PPI 网络进行了整合，并确定了与衰老相关的核心模块和节点。最后，我们计算了衰老网络与不同肝脏疾病和再生网络的网络接近度，以量化衰老的影响。我们的分析揭示了衰老肝脏中免疫、癌症信号和代谢基因的复杂相互作用。我们发现衰老与 NAFLD、HCC、肝损伤状况以及肝脏再生早期之间存在显著的网络接近度，共同的节点包括 NLRP12、TRP53、GSK3B、CTNNB1、MAT1 和 FASN。总的来说，我们的研究描绘了衰老的网络水平变化及其与肝脏生理学和病理学的相互联系。
