Stanford study finds blocking one receptor slows aging in mice

A study published in the journal Science on Wednesday reveals that blocking a single receptor on immune cells can restore the body's ability to clear senescent "zombie" cells, preventing cognitive decline, frailty, and weight gain in aging mice. The research, led by a team at Stanford University, points to a potential new avenue for anti-aging therapies in humans.

Macrophages Lose Their Appetite With Age

The study, led by neurologist Katrin Andreasson, focuses on tissue-resident macrophages — immune cells responsible for clearing defunct cells from the body. Among their primary targets are neutrophils, short-lived white blood cells that enter a senescent state when they fail to encounter pathogens. These senescent neutrophils accumulate in tissues over time, driving chronic inflammation.the-scientist+1

"Senescent neutrophils are killing our tissues," Andreasson said in a statement. "Clearance of these cells is essential for preventing chronic inflammation."the-scientist

The researchers traced the age-related decline in macrophage performance to prostaglandin E2, an inflammatory molecule that overstimulates a receptor called EP2 on macrophages' surfaces, suppressing their metabolism and ability to engulf damaged cells.science+1

An Experimental Drug Mimics Genetic Protection

In mice aged 23 to 25 months — equivalent to humans in their 60s or 70s — the team found changes in 71 blood proteins associated with aging. But older mice genetically engineered to lack EP2 on their macrophages retained youthful levels of most of these proteins, showed greater muscle mass, better organ function, and memory performance nearly matching that of young mice.the-scientist

The researchers then tested an experimental oral drug that specifically inhibits EP2 in older, unmodified mice. The drug reduced senescent neutrophil counts toward more youthful levels. The team also observed similar cellular changes in human tissue samples, suggesting the findings could eventually translate to people.science+1

A Difficult Target

Despite the promising results, Andreasson cautioned that EP2 sits at the center of a complex metabolic pathway. No approved drugs currently target this receptor, and common anti-inflammatory painkillers that work on related processes are too non-specific. "EP2 will be a difficult target to hit precisely," she said, noting that further work is needed before clinical translation.the-scientist