Longevity & AgingHow Exercise Turns Damaged Mitochondria Into a Muscle-Boosting Signal Molecule
Researchers discovered that endurance exercise triggers mitophagy — the cellular cleanup of damaged mitochondria — in slow-twitch muscle fibers, releasing ceramides that are converted into sphingosine-1-phosphate (S1P) via the enzyme SPHK1. This S1P then activates receptors S1PR1 and S1PR2, which are uniquely enriched in slow-twitch fibers in both mice and humans, promoting mitochondrial biogenesis and improving endurance capacity. Blocking this pathway impaired exercise adaptation, while administering S1P externally improved endurance in muscle-atrophy mouse models. The findings identify a previously unknown sphingolipid signaling axis as a central mediator of exercise-induced muscle adaptation, with potential therapeutic implications for muscle-wasting diseases like Duchenne muscular dystrophy and sarcopenia.
