Restoring myeloid metabolism and efferocytosis to attenuate inflammaging

Tissue-resident macrophages (TRMs) are crucial for clearing senescent neutrophils via efferocytosis, thereby preventing chronic inflammation and tissue damage. However, whether this clearance mechanism fails with age and actively drives organ decline has been unclear. A recent study by Tan et al. reveals that aberrant prostaglandin E₂ (PGE₂)–PGE 2 receptor EP2 signaling in aged TRMs suppresses mitochondrial metabolism and efferocytic function, allowing senescent neutrophils to accumulate and propagate systemic inflammaging. Remarkably, genetic ablation or pharmacological inhibition of EP2 restores TRM clearance capacity and reverses multiple aging phenotypes. These findings reframe aging as a failure of active cellular clearance rather than passive degeneration, positioning TRM EP2 as a promising therapeutic target for age-related pathology.