A Science paper from Stanford Medicine researchers linked organ aging to breakdown in tissue-resident macrophage clearance of senescent neutrophils. The group reported that advancing age impairs tissue-resident macrophage (TRM) ability to clear aged neutrophils, contributing to organ-wide decline. In mouse models and human cell experiments, blocking the EP2 receptor on TRMs preserved a more youthful state across multiple organs, including brain, heart, muscle, liver, spleen, bone marrow, kidney, and colon. The team also reported that selective genetic disruption of EP2 in TRMs or an experimental EP2 antagonist drug prevented inflammation-associated disorders such as frailty and supported cognitive function. The findings frame aging as a failure of active cellular clearance rather than passive degeneration and point to EP2 signaling as a druggable target for healthspan-focused interventions.