Xie, Q.; Lin, T. D.; Jang, S.; Jan, C.; Selahi, A.; Nyberg, K.; Wendorff, A. A.; Hake, K.; Lefebvre, A. E. Y. T.; Jin, M.; Di Francesco, A.; Pokrovskii, M.; Tauc-Adrian, H.; Kenyon, C.

Adipose tissue exhibits pronounced inflammation during aging, yet the mechanisms sustaining this chronic state are not well understood. By creating an atlas integrating histology, single-nucleus transcriptomics and flow cytometry across the murine lifespan, we find that age-associated inflammation is distinct from the obesity-like inflammatory profile observed at mid-life. Specifically, age-associated inflammation is characterized by a potent interferon-gamma (IFN{gamma}) response signature and the accumulation of T cells. We demonstrate that senescent cells act as an upstream trigger, indirectly initiating an IFN{gamma} response that upregulates vascular MHC II to promote extravasation of CD4+ T cells into the aging tissue. These recruited T cells then act as a critical source of IFN{gamma}, thereby perpetuating a positive feedback loop that maintains chronic immune infiltration and tissue inflammation. These results provide a multi-modal view of adipose aging and identify a mechanism that sustains its age-associated inflammation.