p21+TREM2+ Senescent Macrophages Drive Inflammaging and MASLD, Reversed by Senolytics

A Nature Aging study identifies a distinct population of p21+ Trem2+ senescent macrophages as major drivers of inflammaging. These cells exhibit a SASP and type I interferon signaling driven in part by cytosolic mitochondrial DNA, accumulate in aging livers and in metabolic dysfunction-associated steatotic liver disease (MASLD), and are distinct from classic M1/M2 macrophages. In both mouse models and human tissue, senolytic treatment with ABT-263 reduces liver inflammation and steatosis, supporting macrophage senescence as a tractable target for aging-related liver disease.