m(6)A RNA Methylation in aging and age-related diseases

Despite advances in prevention and treatment, aging and age-related diseases remain major causes of morbidity and mortality worldwide. N6-methyladenosine (m6A) is a prevalent internal modification of eukaryotic mRNA that regulates RNA splicing, export, stability, translation, and decay. In this comprehensive narrative review, we synthesize current evidence on the dynamic, tissue- and context-dependent remodeling of m6A during aging and in selected age-related pathologies. We emphasize how m6A functions as a post-transcriptional rheostat that complements canonical transcriptional and signaling pathways by controlling the fate of specific RNA transcripts. We discuss mechanistically supported roles of m6A in cellular senescence, the senescence-associated secretory phenotype, autophagy, oxidative stress, and organ dysfunction, while distinguishing established mechanisms from emerging or conflicting observations. We also critically evaluate the potential and current limitations of m6A regulators as biomarkers and therapeutic targets. By integrating evidence from human samples, animal models, and cellular systems, this review defines current knowledge gaps and outlines priorities for future mechanistic and translational research in aging.