Transcriptomic analysis reveals the function of m6A regulators in aged cochlea

Abstract

Objective: Presbycusis is a prevalent health issue among the elderly. Previous studies have shown mechanisms related to this condition, but the underlying mechanisms of presbycusis remain elusive. N6-methyladenosine (m6A) modification in regulating gene expression and cellular functions has been implicated in the development of various diseases. Nevertheless, the potential role of m6A regulators in presbycusis is still unclear. In this study, we aim to determine the expression of m6A regulators in the cochleae of young and old mice, and to investigate their potential role in aging. Methods: We sequenced the transcriptome from the cochleae of six young (2-mo) and six old mice (24-mo) bioinformatics analysis. Differential expression analysis and downstream functional analysis was performed to identify m6A regulators. Association of m6A regulators with protein-protein interaction and transcription factor-miRNA networks were constructed to explore their regulatory mechanisms. Results: ALKBH5 and YTHDC1 were found upregulated in the aged cochleae. They were strongly correlated with immune-related pathways, immune molecular subtypes, and immune infiltration levels in old mice, suggesting their potential involvement in immune-related mechanisms of presbycusis. Receiver Operating Characteristic (ROC) curve analysis demonstrated the high diagnostic potential molecules of AlkB Homolog 5 (ALKBH5) and YTHDC1. Conclusion: This study has established a molecular foundation and introduce a novel perspective on the role of m6A regulators in presbycusis, emphasizing ALKBH5 and YTHDC1 as potential markers. Level of evidence: Acknowledging methodological similarities with Level 3 (non-randomized controlled cohort or case-control studies) in clinical research, we reference Level 3 as a comparative framework, while recognizing the distinct differences between clinical and animal research settings.

Keywords

• Aged cochlea
• m6A regulators
• Transcriptomics
• Mice
• Immune-related genes