Age-Related Thymic Atrophy: Mechanisms and Outcomes

Age-related thymic atrophy or involution, a hallmark of thymic aging, takes place both in humans and animals. In this chapter, we will discuss age-related thymic atrophy, outlining the underlying cellular and molecular mechanisms of its occurrence. We will also address the downstream influences on the aged T cell immune system, not only regarding insufficiency against pathogens, but also hyper-reactivity to self. Particularly, we will focus on how thymic atrophy disrupts efficient establishment of central T cell immune tolerance primarily via impairment of thymocyte negative selection, resulting in an increased number of self-reactive conventional T cells, and on thymic-derived regulatory T cell generation. Finally, we will provide a framework for understanding the significant role that the atrophied thymus plays in shaping inflammaging: a chronic, low-grade, systemic inflammatory phenotype observed in aged individuals in the absence of acute infection. The involvement of T cell adaptive immunity in mediating inflammaging plays a crucial role in the progression of many age-related neurological and cardiovascular diseases.