Restoring ability to remove zombie cells may keep us sharp as we age
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- Stanford researchers led by Katrin Andreasson found that older mice lose the ability to clear senescent neutrophils because prostaglandin E2, a signalling molecule that rises with age, overstimulates the EP2 receptor on tissue-resident macrophages and cripples their cleanup function.
- Genetically modifying EP2 in older mice's macrophages restored senescent-cell clearance and produced lower inflammation, reduced muscle loss, less visceral fat, better mobility, and near-young performance in memory tests compared with unmodified same-age mice.
- An experimental oral EP2-blocking drug given to older mice for two months produced similar age-related improvements with no known side effects reported in the study.
- Derek Gilroy at University College London, who was not involved in the research, cautioned that EP2 is part of normal body signalling and warned whole-body blocking could have unwanted effects, suggesting it may be safer to target EP2 in ageing macrophages specifically.
- Liver samples from older humans showed higher EP2 activity and more senescent neutrophils — a pattern matching the mouse data, though Gilroy noted the human evidence remains correlative and has not yet shown that blocking EP2 restores clearance in aged human tissue.
- Andreasson's team is now planning to investigate whether the same pathway affects the onset of conditions such as Alzheimer's disease.
Why it matters: Unlike most anti-ageing approaches that try to kill senescent cells directly, this Stanford study targets the immune system's declining cleanup machinery via a single receptor — and an oral drug achieved comparable results in mice, making human translation more feasible than cell-killing strategies. Researchers are now extending the work to Alzheimer's, which could sharply raise the stakes if the EP2 pathway also governs neurodegenerative disease onset.
