Derivation and comprehensive analysis of ageing-related genes in intervertebral disc degeneration for prediction and immunology

• Published in: Mechanisms of ageing and development 2023-04, Vol.211, p.111794-111794, Article 111794
• Main Authors: Xu, Shengxiang, Fu, Huichao, Weng, Shiyang, Gu, Xin, Li, Jieruo
• Format: Article
• Language: English
• Subjects: Aging - genetics; Differential ageing-related genes (DARGs); Gene Expression Regulation; Humans; Immunology; Intervertebral Disc - metabolism; Intervertebral disc degeneration; Intervertebral Disc Degeneration - genetics; Intervertebral Disc Degeneration - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Network pharmacology; RNA, Messenger - metabolism; Transcription factor
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2023.111794

Intervertebral disc degeneration (IDD) is triggered primarily by ageing, a process characterized by intrinsic, multifaceted and progressive characteristics. Regarding the crucial senescence genes and underlying regulatory mechanisms leading to the etiology of IDD, there is still some uncertainty. In this study, we used gene expression patterns from the GEO database to create a diagnostic model of IDD using differential ageing-related genes (DARG). We examine the relative dynamics of immune cells by single-sample gene set. On the basis of transcription factor (TF) miRNA and miRNA-mRNA pairs, the regulatory network for transcription and post-transcriptional processes was built. The active therapeutic components and Chinese herbal remedies of the main ageing genes were investigated using a network pharmacology approach. 20 DARGs were combined to create a diagnostic model, and both the training and validation sets had an area under the ROC curve of 1. We found alterations in many cell types in IDD tissue, but mainly in activated dendritic cells, type 17 T helper cells, and mast cells. We identified a regulatory axis for STAT1/miR-4306/PPARA based on the correlations between gene expression and targeting. Active substances (Naringenin and Quercetin) and herbs (Aurantii fructus and Eucommiae cortex) targeting PPARA for the treatment of IDD were discovered through network pharmacology. These results provide a theoretical framework for identifying and treating IDD. For the first time, we were able to diagnose IDD patients using 20 ageing-related indicators. At the same time, TF-miRNA-mRNA in conjunction with network pharmacology enabled the identification of prospective therapeutic targets and pharmacological processes. [Display omitted] •A model based on 20 differential ageing-related genes (DARGs) is a valuable diagnostic feature for intervertebral disc degeneration (IDD).•Naringenin and quercetin may hasten the development of IDD by binding to PPARA.•The DARGs are closely associated with cellular infiltration, especially in Th17 cells, in IDD.