Alternative splicing in aging and aging-related diseases: From pathogenesis to therapy

Aging is a complex biological process associated with nearly all diseases. Alternative splicing is increasingly recognized as an important contributor to aging and a key research pathway for extending human lifespan. In this review, we highlight the findings of alternative splicing in the hallmarks of aging including key processes such as genomic instability, telomere length, protein stability, autophagy processes, etc., as well as antagonistic hallmarks of aging such as various metabolic signals, energy metabolism, clearance of senescent cells, stem cell self-renewal, cell communication and inflammatory process, etc. We also discuss the roles of alternative splicing in age-related diseases, including neurodegenerative diseases, cardiovascular diseases, skeletal muscle-related diseases, metabolic disorders, cancer, sensory degeneration, and chronic inflammation, etc. These studies suggest that new anti-aging therapies could be developed by regulating key splicing proteins or specific splicing events.