Background: The major function of Malassez's epithelial rest (ERM) cells is thought to be maintenance of the homeostasis of the periodontal ligament. The purpose of this study was to investigate the effect of aging on the functions of ERM cells in vitro. Methods: ERM cells cultured from porcine teeth were used in this study, and cells at passages 3, 11 and 17 were analyzed by DNA microarray to evaluate gene expression profiles. Furthermore, quantitative real-time RT-PCR was performed to confirm the microarray data for selected genes. Results: The microarray data revealed that approximately 4,300 of the 21,123 genes on the array were expressed at significantly different levels. Among them, 230 genes, including BMP2, were significantly decreased between the 3rd to the 11th passage. Moreover, 23 genes, including beta-defensin1, MMP13 and CD61, were significantly down-regulated from the 3rd to the 11th and from the 11th to the 17th passages(P<0.05). Conclusion: These results suggest that cementogenesis, antibacterial effects, collagenase activity and cell adhesive functions of the ERM are affected by aging.