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Periodontal ligament cells (PDLC) play a major role in periodontal tissues homeostasis and destruction. Most age-associated diseases seem to be closely related to an underlying chronic inflammatory state. Thus, the present study aimed at evaluating in PDLC the effect of aging on the basal levels of inflammatory and bone-related genes. Primary PDLC cultures were obtained from subjects aged 15–20 years (control- n = 5), and subjects aged more than 60 years (test- n = 5). Proliferation, cell viability and total secreted protein assays were performed, and mRNA levels were quantitatively assessed for interleukin (IL)-1β, IL-4, IL-6 and IL-8, and for receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) by real time PCR. Data analysis demonstrated that aging negatively influenced cell proliferation, whereas cell viability and total secreted protein were not affected (p > 0.05). Gene expression analysis showed that mRNA levels for RANKL and IL-8 were not affected by aging (p > 0.05) whereas, mRNA levels for IL-4 was significantly lower in aged cells (p < 0.05) and OPG, IL-1β and IL-6 mRNA levels were higher (p < 0.05). Data analysis suggests that aging decreased the ability of PDLC to proliferate and modulated the expression of important inflammatory and bone-related genes in periodontal ligament cells, favoring a proinflammatory and an antiresorptive profile.