Fig. 1

Intersection of immunosenescence and inflammaging is associated with age-related thymic involution. The aged, involuted thymus exhibits ineffective central tolerance and declined thymopoiesis. The ineffective central tolerance includes (1) impaired negative selection, which leads to the increased output of self-reactive T cells that attack self-tissues/organs, and (2) imbalanced generation of tTreg TCR repertoire, which fails to sufficiently suppress self-reactive T cell–mediated autoimmune responses. Autoimmune responses lead to tissue damage and thus cause chronic inflammation, which is one of the contributors to inflammaging. Reduced thymopoiesis leads to decreased output of naïve T cells for the clearance of senescent somatic cells (SSCs) and the expansion of oligo-clonal T cells in the aged periphery lack sufficient clearance capacity, which allows for SSC accumulation. SSCs are an important source of SASP, another contributor to inflammaging