Sarcopenia is an aging-associated muscle wasting disease that lacks good treatment options. In this manuscript the authors show that blocking the activity of a single protein called 15-PGDH in old mice for one month restores mass and strength to the animals’ withered muscles and helps them run longer on a treadmill, rejuvenating their muscles. Conversely, increasing the abundance of the protein in young mice causes their muscles to atrophy and weaken, effectively prematurely aging the muscles of these mice. 15-PGDH breaks down another molecule called PGE2. Blocking its activity effectively increases the amount of PGE2 present in aged muscles. PGE2 signaling in turn impacts cellular pathways to ameliorate muscle atrophy and rejuvenate muscle function. 15-PGDH may be a suitable therapeutic target for countering sarcopenia.