Carnosine drives mitochondrial biogenesis and skeletal muscle regeneration via Sirt1-mediated nuclear translocation of PGC-1α.

Abstract

Post-injury skeletal muscle regeneration depends on the proliferation and differentiation of satellite cells, and mitochondrial function acts as an essential prerequisite for this biological process. This study shows carnosine promotes mouse C2C12 myoblast proliferation, up-regulates mitochondrial genes, and activates oxidative phosphorylation and ATP synthesis. In mechanism, it promotes PGC-1α nuclear translocation, TFAM expression, mitochondrial biogenesis and ATP production. The pharmacological inhibition of Sirt1 by EX-527 eliminated the nuclear accumulation of Sirt1 and PGC-1α induced by carnosine, which confirmed that Sirt1 is an important mediator. Animal experiments confirmed that oral carnosine could accelerate the repair of injury, increase regenerated muscle fibers on the 7th day, and up regulate Pax7, myogenic differentiation 1 (MyoD) and myogenin (MyoG). Molecular docking showed that carnosine could bind to Sirt1 protein. This study clarified that carnosine can drive mitochondrial biogenesis by targeting Sirt1/PGC-1α/TFAM signaling axis, thus promoting myogenesis and muscle repair, providing a theoretical basis for the clinical application of carnosine.