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

JOURNAL/agad/04.03/02274129-202601000-00002/figure1/v/2026-04-20T115955Z/r/image-tiff 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.