Objective: The current study was performed to test the hypothesis that periodontal disease produces age-dependent activation of apoptotic markers in the gingival tissues. Methods: To address the hypothesis a prospective experimental study was designed and twenty-two patients were enrolled. Out of the twenty-two patients, gingival tissue biopsies samples were obtained from active sites of ten and twelve periodontal-healthy (HS) and periodontal disease (PD, probing depths >5 mm patients, respectively. The groups were further divided into 25-50 and 50 years age group compared to respective HS age groups. PD patients of both 25-50 years and >50 years age exhibited a significant increase in the expression of Cytochrome C and Caspase-3 compared to the respective HS groups. The PD patients exhibited a stronger correlation with age in the expression of TRADD and Bax compared to the HS groups. Further analyses revealed that the expression of Caspase-3 correlated with an increase in the age of the healthy patients. Conclusions: The data suggested that modulation of apoptotic cascade may contribute to the damage of gingival tissues particularly in PD patients >50 years age. © 2009 Elsevier Ltd. All rights reserved.