The gradual decline that comes with ageing may have less to do with the passing of time and more to do with an overworked immune system failing to clear away worn-out cells, according to a Stanford Medicine study that could reshape future treatments for age-related diseases.

Published in the journal Science, the research identifies tissue-resident macrophages—long-lived immune cells that quietly patrol organs and remove damaged cells—as key players in keeping the body healthy. Researchers discovered that as we age, these immune cells work less effectively because of too much activity from a receptor called EP2, which responds to the inflammatory hormone prostaglandin E2 (PGE₂). The result is a build-up of ageing, "zombie-like" neutrophils—short-lived white blood cells that should normally be cleared before they begin damaging surrounding tissues. The findings were seen in mice and supported by analyses of human liver cells. Human clinical trials have yet to begin.

"We've been trying to figure out why we age," said senior author Katrin Andreasson, professor of neurology and neurological sciences at Stanford Medicine. "Now we know at least one big reason for it."

In healthy adults, macrophages remove roughly 100 billion ageing neutrophils every day. The Stanford team found that this natural clean-up operation weakens over time, allowing harmful cells to accumulate and fuel the chronic, low-grade inflammation that scientists increasingly recognise as a hallmark of ageing. Previous studies, including Andreasson's 2021 Nature paper and wider research on "inflammaging", have similarly linked persistent inflammation to dementia, cardiovascular disease, frailty and metabolic disorders.

The researchers genetically removed the EP2 receptor from tissue-resident macrophages in older mice and also tested an experimental EP2-blocking compound. Both approaches restored the immune cells' ability to dispose of worn-out neutrophils. Older mice retained better memory, stronger grip strength, healthier muscles, lower abdominal fat and reduced inflammation across organs, including the brain, liver, heart, kidneys and colon.

"Senescent neutrophils are killing our tissues," Andreasson said. "Clearance of these cells is essential for preventing chronic inflammation."

No medicine currently targets EP2 specifically, and researchers caution that much more work is needed before similar treatments can be tested safely in people. Even so, the discovery strengthens a growing scientific view that slowing biological ageing may depend less on fighting time itself and more on restoring the immune system's natural housekeeping—an approach that could one day help millions spend more years living independently rather than simply living longer.