Age-related thymic involution: Mechanisms and functional impact

The thymus is the primary immune organ responsible for generating self-tolerant and immunocompetent T cells. However, the thymus gradually involutes during early life resulting in declined naive T-cell production, a process known as age-related thymic involution. Thymic involution has many negative impacts on immune function including reduced pathogen resistance, high autoimmunity incidence, and attenuated tumor immunosurveillance. Age-related thymic involution leads to a gradual reduction in thymic cellularity and thymic stromal microenvironment disruption, including loss of definite cortical-medullary junctions, reduction of cortical thymic epithelial cells and medullary thymic epithelial cells, fibroblast expansion, and an increase in perivascular space. The compromised thymic microenvironment in aged individuals substantially disturbs thymocyte development and differentiation. Age-related thymic involution is regulated by many transcription factors, micro RNAs, growth factors, cytokines, and other factors. In this review, we summarize the current understanding of age-related thymic involution mechanisms and effects.