Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function

The gradual decline in thymic function with age, known as age-related thymic involution, leads to reduced T cell production, thereby increasing the risk of infections and cancer susceptibility and leading to poor vaccine responses. Moreover, T cell defects were recently involved in the age-related loss of tissue integrity and function. Mechanistically, thymic involution is driven by several factors, including hormonal modifications and chronic inflammation, leading to functional changes in the hematopoietic and stromal compartments. These progressive changes alter the cross-talk between developing T cells and thymic epithelial cells, which is pivotal for thymic function. Promising strategies to counteract thymic involution and rejuvenate immune T cell function have been recently identified. This review summarizes key insights into the underlying mechanisms of thymic involution and discusses current and emerging rejuvenation strategies to restore thymic function. These interventions show promise in regenerative medicine to promote healthy aging by alleviating age-associated immune decline.