Epithelial-mesenchymal transition in age-associated thymic involution: Mechanisms and therapeutic implications

The thymus is a critical immune organ with endocrine and immune functions that plays important roles in the physiological and pathological processes of the body. However, with aging, the thymus undergoes degenerative changes leading to decreased production and output of naive T cells and the secretion of thymic hormones and related cytokines, thereby promoting the occurrence and development of various age-associated diseases. Therefore, identifying essential processes that regulate age-associated thymic involution is crucial for long-term control of thymic involution and age-associated disease progression. Epithelial-mesenchymal transition (EMT) is a well-established process involved in organ aging and functional impairment through tissue fibrosis in several organs, such as the heart and kidney. In the thymus, EMT promotes fibrosis and potentially adipogenesis, leading to thymic involution. This review focuses on the factors involved in thymic involution, including oxidative stress, inflammation, and hormones, from the perspective of EMT. Furthermore, current interventions for reversing age-associated thymic involution by targeting EMT-associated processes are summarized. Understanding the key mechanisms of thymic involution through EMT as an entry point may promote the development of new therapies and clinical agents to reverse thymic involution and age-associated disease.