The majority of patients eligible for periodontal regenerative therapies are aged subjects. Since periodontal ligament cells (PDLC) are essential for periodontal regeneration, the aim of the present study was to determine the effect of cellular aging on PDLC, including genes associated with extracellular matrix metabolism and growth-associated factors. PDLC cultures were obtained from subjects aged 15 to 20 years and subjects aged more than 60 years. Proliferation, cell viability, mineralization assays, and mRNA levels were assessed for type I and III collagen, platelet-derived growth factor (PDGF)-1, basic fibroblast growth factor (bFGF), metalloproteinase (MMP)-2 and-8, and tissue inhibitor of metalloproteinases (TIMP)-1 and-2. Data analysis demonstrated that aging negatively influenced cell proliferation and mineral nodule formation (p < 0.05). Gene expression analysis further showed that mRNA levels for bFGF, PDGF-1, and TIMP-2 were not affected by aging (p > 0.05). In addition, mRNA levels for type I and III collagen were significantly lower in aged cells (p < 0.05), whereas MMP-2 and-8 and TIMP-1 mRNA levels were higher (p < 0.05). Within the limits of the present study, data analysis suggests that aging modulates important biological properties of periodontal ligament cells, diminishes the potential for mineral nodule formation, and favors extracellular matrix degradation.