This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ntroduction: The susceptibility of the periodontal tissues to plaque-induced periodontal disease may be influenced by the aging process. We hypothesize that aging of periodontal tissues causes changes in the expression of proteins critical for inflammation and tissue regeneration. This results in greater disease susceptibility and lower healing potential in aged subjects. We are using cellular replicative senescence as an in vitro model of aging.Methods: Gingival tissue from young and old patients with and without periodontal disease was examined using microarrays. Senescent cells were compared to rapidly dividing cells using microarrays, RT-PCR and cell proliferation assays and apoptosis dyes. Heat-killed periodontal pathogen P.gingivalis was added to the cultures to simulate periodontal infection in vitro. Additionally, apoptosis-inducing molecules were added to the cell cultures to study the effects of senescence on apoptosis. Results: The following are the results for year 4. Microarray analysis of gingival tissues revealed few changes with aging, while the changes from health to disease were far more pronounced. Microarray analysis of senescent versus rapidly dividing cells showed several classes of molecules that were differentially expressed, including; attachment and extracellular matrix proteins, cytokines and growth factors, cyclins, histones and genes involved in apoptosis. Many of these genes were increased in senescent cells. The addition of P. gingivalis to rapidly dividing cells showed parallel trends to those observed in senescence. Senescent gingival fibroblasts seem more sensitive to apoptosis, but the transition from apoptosis to necrosis may be delayed in these cells.Discussion: Cellular senescence of gingival fibroblasts results in changes in the expression of numerous genes compared to rapidly dividing gingival fibroblasts. Also, there seems to be a role of cellular senescence in determining increased susceptibility to apoptosis in gingival tissues with aging
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