Objective:To study the mechanisms of cardiomyocytes aging induced by advanced glycation end products. Methods:Neonatal rat cardiac myocytes were cultured with AGEs,anti-RAGE antibody for 48 h. Senescence-associated beta galactosidase (SA-β-Gal) activity was observed via SA-β-Gal assay in neonatal rat cardiomyocytes. p53,p16,LC3 and Beclin1 were measured by Western blot. We observed mitochondrial membrane potential and the generation of reactive oxygen species(ROS) by JC-1 and DCFH-DA methods. Results:After intervention for 48 h with AGEs,SA-β-Gal activity and the expression of p53(P < 0.01),p16(P < 0.01),LC3(P < 0.01) and Beclin1(P < 0.01) were significantly increased in the AGEs group compared to that of the control group,accompanied by the significantly decrease of mitochondrial membrane potential (P < 0.01) and remarkably increase of ROS(P < 0.01). After treated with anti-RAGE antibody,SA-β-Gal activity and the level of p53(P < 0.01),p16 (P < 0.01),LC3 (P < 0.05)and Beclin1(P < 0.01)were remarkably decreased compared with the AGEs group. However,inhibition of RAGE with anti-RAGE antibody remarkably increased mitochondrial membrane potential(P < 0.01) and significantly decreased ROS compared with AGEs group(P < 0.01).Conclusion:AGEs-RAGE may induce aging of cardiomyocytes by mitochondrial damage,the generation of ROS and autophagy.