GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304476/primaryOK200TranscriptomicsMus musculus OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304476GEOGSEfalseInflammaging in aged tissues drives remodeling of the CD8+ T cell compartmentAging 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 (TAA cells). Although TAA cells make up a significant fraction of the aged CD8+ T cell compartment, the pathway underlying their differentiation remains unknown. In this study, we demonstrate that TAA cell development is cell-extrinsic and requires antigen exposure within aged non-lymphoid tissues. Using a novel TNFΔ69AU/+ mouse model, we show that systemic low-grade inflammation, characteristic of inflammaging, accelerates CD8+ T cell aging and promotes early accumulation of TAA cells. Through detailed analysis of TAA 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.2026/03/23GSE304476GSM9151228GSM9151227GSM9151226GSM9151225GSM9151219GSM9151229GSM9151231GSM9151220GSM9151230GSM9151224GSM9151223GSM9151222GSM9151233GSM9151232GSM915122134290304476Mus musculus