Objective:To investigate the mechanisms of cardiac fibroblasts aging and fibrosis induced by advanced glycosylation end-productcs(AGEs). Methods:Neonatal rat cardiac fibroblasts were incubated for 72h with AGEs(200 μg/ml),anti-RAGE antibody (2 μg/ml) and TGFβ/smad signaling pathway inhibitor (SB431542,10 μmol/L). Senescence-associated beta galactosidase activity and p16 expression were observed;MMP-2,TGF-β1 and p-smad2/3 were measured by Western blot. Results:After intervened with AGEs for 72 h,senescence-associated beta galactosidase activity and the level of p16 in the AGEs group were significantly increased compared with the control group(P < 0.01),accompanied with significant increases of the expressions of TGF-β1,p-smad2/3 and MMP-2. However,senescence-associated beta galactosidase activity and the expression of p16 were remarkably down-regulated after the pretreatment of anti-RAGE antibody and SB431542 compared with those of the AGEs group,meanwhile,the levels of TGF-β1,p-smad2/3 and MMP-2 were also significantly decreased. Conclusion:We conclude that AGEs could induce cardiac fibroblasts aging through binding to its receptor RAGE,and cardiac fibrosis induced by TGF-β/smad pathway could be involved in this process.