Alternative splicing in aging and age-related diseases

Alternative splicing (AS) of mRNA generates multiple protein isoforms from a single gene. This greatly expands proteome diversity and plays important roles in most biological processes. Global changes occur to AS as cells and individuals age normally and during age-related diseases. Some of these changes play critical roles in aging and associated phenotypes. Although AS has been extensively reviewed with respect to functions and molecular mechanisms in certain biological processes, a comprehensive view of AS is lacking in aging research. In this review, we focus on the functional side of AS in the aging process, and we summarize the age-related genes and splicing types, the potential functional mechanisms, upstream regulators and pathways involved. Global changes to AS during aging and potential therapeutic strategies to correct aberrant splicing are also discussed.