Alternative Polyadenylation in Aging and Aging-Related Diseases

Aging is a major risk factor for a wide range of chronic diseases. Elucidating the molecular mechanisms underlying aging-associated disorders is essential for developing effective preventive and therapeutic strategies. Recent research has unveiled the regulatory roles of non-coding genomic regions. Among these, alternative polyadenylation (APA), a conserved co-transcriptional mechanism, has emerged as a key modulator of gene expression, with an established involvement in various age-related pathologies. APA alters the length of the mRNA 3' untranslated region (3' UTR), thereby affecting mRNA stability, localization, translational efficiency, and ultimately protein expression. Notably, approximately 70% of human genes undergo APA-mediated regulation, underscoring its extensive influence on cellular function. This review summarizes the advances in exploring the role of APA in aging-related diseases, including musculoskeletal disorders, neurodegenerative diseases, cardiovascular and respiratory diseases. These findings can verify the potential of APA as a novel regulatory player in aging biology and a mechanistic contributor to the pathogenesis of age-associated diseases, highlighting its promise as a therapeutic target.