Transcriptomic analysis reveals the function of m6A regulators in aged cochlea

TL;DR

This study finds that ALKBH5 and YTHDC1 are linked to immune changes in aged mouse cochleae and may serve as markers for age-related hearing loss.

Contribution

The study introduces a novel perspective on m6A regulators' role in presbycusis and identifies ALKBH5 and YTHDC1 as potential diagnostic markers.

Findings

ALKBH5 and YTHDC1 are upregulated in aged cochleae.

These regulators are strongly associated with immune pathways and immune cell infiltration.

ROC analysis shows ALKBH5 and YTHDC1 have high diagnostic potential for cochlear aging.

Abstract

•ALKBH5 and YTHDC1 are potential useful diagnostic markers for cochlear aging.•ALKBH5 and YTHDC1 are highly associated with immune pathways.•ALKBH5 and YTHDC1 are highly associated with immune cell infiltrate.

ALKBH5 and YTHDC1 are potential useful diagnostic markers for cochlear aging.

ALKBH5 and YTHDC1 are highly associated with immune pathways.

ALKBH5 and YTHDC1 are highly associated with immune cell infiltrate.

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.

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.

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.

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.

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.

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