Moreover, we designed and successfully applied muscle‐specific promoter MCK driven AAV to mediate the delivery of NLS‐PGC1α4 into gastrocnemius (GAS) muscle and alleviated aging‐associated sarcopenia and metabolic disorders, including adiposity, insulin resistance and fatty liver in mice, at least partially via myokines IGF1 and METRNL to improve muscle and adipose tissue functionality and systemic energy metabolism in aged mice. Here, CKM is linked to metabolic disease.