Thymic involution

Thymic involution is the progressive replacement of thymic epithelial space by adipose tissue that begins at puberty and accelerates thereafter, reducing the organ's capacity to generate naive T cells from bone-marrow-derived precursors. By the sixth decade, thymic output of T-cell receptor-diverse naive T cells is diminished to a small fraction of peak adolescent output, constraining the repertoire available to respond to new antigens. Several thymic regeneration strategies have been investigated, including the TRIIM trial by Fahy and colleagues in which a growth hormone/DHEA/metformin combination was associated with partial epigenetic age reversal, and interleukin-7 administration to support peripheral naive T-cell homeostasis and survival; both approaches remain early-stage and require replication in larger trials before clinical conclusions can be drawn. Improving thymic function is considered a plausible route to partially reversing age-related immune decline.