Aging-associated genes as therapeutic candidates for spinal cord injury: An observational study

Huang, Xiaoyan; Zha, Xiaowei*

Department of Orthopedics, Anhui No. 2 Provincial People’s Hospital, Hefei, Anhui Province, China

*Correspondence to: Xiaowei Zha, MD, xiaowei.zha@stud.uni-heidelberg.de.

Abstract

Objectives:

Aging is inextricably linked to the development of multiple diseases. However, the prognostic significance and therapeutic potential of aging-related genes in spinal cord injury are not fully understood. This study aims to explore the key roles of aging-related genes in spinal cord injury through integrated bioinformatics analysis and experimental validation, identifying core biomarkers and potential therapeutic targets.

Methods:

Transcriptome datasets related to spinal cord injury were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes were identified by comparing injury and control groups and intersecting them with known aging-related gene sets. Hub genes were subsequently determined through four protein–protein interaction algorithms. Finally, drug–biomarker, miRNA–mRNA, and transcription factor–mRNA networks were constructed to uncover potential therapeutic targets and candidate small-molecule compounds. Expression of key hub genes was validated in an independent dataset (GSE183591) and in a rat spinal cord injury model using quantitative reverse transcription-polymerase chain reaction.

Results:

Comparative analysis between spinal cord injury and control groups identified 1396 differentially expressed genes (820 upregulated, 576 downregulated). Protein interaction network analysis positioned cyclin-dependent kinase 1 (CDK1) and the MYC proto-oncogene at the core of the regulatory network. Computational screening predicted their potential regulation by 176 miRNAs, 81 transcription factors, and 85 therapeutic drugs. In both the independent validation dataset and the rat model, CDK1 and MYC expression was significantly upregulated in the injury group, consistent with findings in the discovery cohort.

Conclusion:

By linking aging-related genes to the progression of spinal cord injury, this study advances our comprehension of its molecular mechanisms. CDK1 and MYC were identified as key hub biomarkers, demonstrating their critical roles in modulating neuronal survival and repair pathways. These findings provide novel potential targets for prognostic assessment and targeted therapies in spinal cord injury.

与衰老相关的基因作为脊髓损伤的治疗候选靶点：观察性研究

摘要

目的：衰老与多种疾病的发生发展密切相关。然而，衰老相关基因在脊髓损伤中的预后意义及治疗潜力尚未完全阐明。本研究旨在通过整合生物信息学分析与实验验证，探索衰老相关基因在脊髓损伤中的关键作用，识别核心生物标志物及潜在治疗靶点。

方法：从基因表达综合数据库（GEO）检索脊髓损伤相关转录组数据集。通过损伤组与对照组比较识别差异表达基因，并与已知衰老相关基因集进行交叉分析。随后运用四种蛋白质相互作用算法确定枢纽基因。最终构建药物-生物标志物、miRNA-mRNA及转录因子-mRNA网络，以发掘潜在治疗靶点和小分子化合物候选物。通过定量反转录聚合酶链反应技术，在独立数据集（GSE183591）及大鼠脊髓损伤模型中验证关键枢纽基因的表达。

结果：脊髓损伤组与对照组的比较分析识别出1396个差异表达基因（820个上调，576个下调）。蛋白质相互作用网络分析将周期素依赖性激酶1（CDK1）和MYC原癌基因定位于调控网络核心。计算筛选预测其可能受176种miRNA、81种转录因子及85种治疗药物调控。在独立验证数据集和大鼠模型中，损伤组CDK1和MYC表达均显著上调，与发现队列结果一致。

结论：本研究通过揭示衰老相关基因与脊髓损伤进展的关联，深化了对该疾病分子机制的理解。CDK1与MYC被确认为关键枢纽生物标志物，证实其在调控神经元存活与修复通路中的核心作用。这些发现为脊髓损伤的预后评估和靶向治疗提供了新型潜在靶点。