Stanford Medicine researchers reported that organ aging in mice and human cells is linked to failure of tissue-resident macrophages to clear senescent neutrophils. In work published in Science, the team identified EP2 signaling on tissue-resident macrophages as a central regulator of senescent neutrophil clearance, driving organ decline and cognitive deterioration. Mechanistically, blocking EP2 preserved a more youthful state across multiple organs in mice, including brain, heart, skeletal muscle, liver, spleen, bone marrow, kidney, and colon. The authors reported that genetic removal of EP2 on tissue-resident macrophages or pharmacologic EP2 inhibition substantially limited chronic inflammation-linked phenotypes such as frailty and excess fat accumulation. The study reframes aging as a cellular clearance problem rather than passive degeneration and points to a specific pathway for intervention—an approach that could inform future drug discovery programs targeting systemic inflammation and immune aging drivers.