CKM and metabolic disease: In summary, based on our finding that PGC1α4, a newly defined potent regulator for muscle hypertrophy, were reduced in both transcription level and nuclear localization in skeletal muscle of aged mice, we designed and delivered a AAV9 mediated and MCK driven nuclear localized PGC1α4 in GAS muscle of aged mice and resulted in significant improvements in muscle functionality and systematic metabolic performances, which represents a potent strategy against sarcopenia and aging‐associated metabolic disorders.