15-PGDH

15-PGDH switches prostaglandin signalling off, chemically inactivating prostaglandin E2, a short-range messenger involved in inflammation and tissue repair. It is the rate-limiting step in clearing prostaglandins, which means blocking the enzyme raises prostaglandin E2 rather than lowering it — the opposite of what anti-inflammatories like ibuprofen do. It has become the reference example of a "gerozyme": its activity climbs with age and progressively suppresses regeneration. In mice, blocking it speeds regeneration of bone marrow, colon and liver, restores mass and strength to aged muscle, rebuilds nerve-muscle connections after injury, and, in work published in 2026, reverses the impaired muscle repair caused by semaglutide. The oral inhibitor MF-300 reported positive early safety data in healthy volunteers in September 2025 and in older adults in January 2026, and a randomised, placebo-controlled Phase 2 trial in age-related muscle loss is planned. One caution: the same gene suppresses tumours in colon and lung, so blocking it is not risk-free.