Background: The circadian rhythm is the internal clock that controls sleep-wake cycles, metabolism,cognition, and several processes in the body, and its disruption has been associated with aging. Thedifferentiated embryo chondrocyte (Dec) gene is related to circadian rhythm. To our knowledge, there areno reports of the relationship between dec gene expression and KRG effect. Therefore, we treated Decgene knockout (KO) aging mice with KRG to study anti-aging related effects and possible mechanisms. Methods: We evaluated KRG and expression of Dec genes in an ototoxicity model. Dec genes expressionin livers of aging mice was further analyzed. Then, we assessed the effects of DEC KO on hearing functionin mice by ABR. Finally, we performed DNA microarray to identify KRG-related gene expression changesin mouse liver and assessed the results using KEGG analysis. Results: KRG decreased the expression of Dec genes in ototoxicity model, which may contribute to itsanti-aging efficacy. Moreover, KRG suppressed Dec genes expression in liver of wild type indicating inhibitionof senescence. ABR test indicated that KRG improved auditory function in aging mouse,demonstrating KRG efficacy on aging related diseases. Conclusion: Finally, in KEGG analysis of 238 genes that were activated and 158 that were inhibited by KRGin DEC KO mice, activated genes were involved in proliferation signaling, mineral absorption, and PPARsignalingwhereas the inhibited genes were involved in arachidonic acid metabolism and peroxisomes. Ourdata indicate that inhibition of senescence-related Dec genes may explain the anti-aging efficacy of KRG.