Comprehensive Transcriptomic Profiling of m6A Modification in Age-Related Hearing Loss

Area of Science:

• Otolaryngology
• Epigenetics
• Molecular Biology

Background:

• Age-related hearing loss (ARHL), or presbycusis, affects 70-80% of individuals over 65.
• ARHL pathogenesis is complex and multifactorial, with epigenetic dysregulation implicated.
• The role of N6-methyladenosine (m6A) modification in ARHL remains unclear.

Purpose of the Study:

• To investigate the role of m6A modification in ARHL.
• To identify differentially m6A-methylated genes in ARHL cochlear tissues.
• To explore potential therapeutic targets for ARHL.

Main Methods:

• Confirmation of m6A downregulation in ARHL cochlear tissues.
• Analysis of m6A regulators (WTAP, METTL3, ALKBH5, FTO) expression in ARHL mice.
• Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) to identify differentially methylated genes.
• Gene Ontology (GO) and KEGG pathway analyses.

Main Results:

• m6A modification regulators were significantly downregulated in ARHL mice.
• 3438 differentially m6A-methylated genes identified (1332 hypermethylated, 2106 hypomethylated).
• 262 genes showed significant differences in both mRNA expression and m6A methylation.
• These 262 genes were primarily enriched in the PI3K-AKT signaling pathway.

Conclusions:

• Differential m6A methylation patterns are present in ARHL cochlear tissues.
• m6A modification plays a role in ARHL pathogenesis.
• Findings provide a basis for further ARHL research and potential therapeutic strategies.