Inflammaging in aged tissues drives remodeling of the CD8 ⁺ T cell compartment

Aging profoundly reshapes the immune cell landscape, with particularly strong effects on CD8 ⁺ T cells, including a marked decline in naïve cells and the emergence of age-associated GZMK ⁺ CD8 ⁺ T cells (T _AA cells). Although T _AA cells make up a significant fraction of the aged CD8 ⁺ T cell compartment, the pathway underlying their development remains unknown. In this study, we demonstrate that T _AA cell development is cell-extrinsic and requires antigen exposure within aged non-lymphoid tissues. Using a novel TNF ^Δ69AU/+ mouse model, we show that systemic low-grade inflammation, characteristic of inflammaging, accelerates CD8 ⁺ T cell aging and promotes early accumulation of T _AA cells. Through detailed analysis of T _AA cell heterogeneity, we identified a progenitor subpopulation enriched in the aged adipose tissue. Using heterochronic transplantation, we show that adipose tissue acts as a functional niche, supporting progenitor maintenance and driving the conversion of young CD8 ⁺ T cells into the aged phenotype. Taken together, our findings reveal how aging of non-lymphoid tissues orchestrates the reorganization of the CD8 ⁺ T cell compartment and highlight adipose tissue as a promising target for therapeutic strategies aimed at modulating immune aging.