Organoids in aging research: Decoding mechanisms, accelerating interventions, and bridging translation

Aging, as a process of gradual decline in cellular and tissue function, poses a major challenge for healthcare systems worldwide. However, traditional models (experimental animals and 2D cell cultures) struggle to reproduce the complexity of human aging, which limits the depth of mechanistic understanding. Organoids, defined as self-organizing 3D stem cell-derived structures that replicate key organ features, have effectively addressed this research gap. This article reviews the applications of organoids in the study of aging, including their core principles, methods for generating common organoid types, advantages, and limitations. The validation processes and mechanisms of the aging model are also discussed. In addition, the applications of brain organoids in research on Alzheimer’s disease and Parkinson’s disease, heart organoids in research on myocardial aging, and liver and islet organoids in research on diabetes are emphasized. Despite advances in single-cell sequencing, gene editing, and imaging technologies, challenges such as standardization and vascularization remain. Nevertheless, organoids have accelerated the development of anti-aging drugs and personalized medicine, thus becoming indispensable tools for understanding the mechanisms of human aging and developing interventions to extend healthy life span.