Senescent cells key to periodontal health

Dental Tribune International

Tue. 13. May 2025

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PHILADELPHIA, US: Periodontal disease affects nearly 60% of adults over the age of 65 and imposes a considerable burden—medically, psychologically and financially. In light of these impacts, recent research conducted at Penn Dental Medicine suggests that an approach which targets senescent cells—cells that have permanently ceased dividing typically in response to stressors—may offer an innovative strategy for improving periodontal health.

According to Dr Sinem Esra Sahingur, the senior author of a paper on a new drug therapy, targeting senescent cells may help manage and potentially reverse periodontal disease. (Image: Penn Dental Medicine)

Senescent cells are known to secrete pro-inflammatory molecules that damage surrounding tissue, impair healing and accelerate disease progression. Previous studies by the Penn Dental Medicine team demonstrated that chronic periodontitis can induce cellular senescence even in younger tissue. Building on this, a new translational study led by Dr Sinem Esra Sahingur, associate professor in the Department of Periodontics and associate dean of graduate studies and student research at Penn Dental Medicine, has explored how targeting senescent cells can help in the management of periodontitis.

“Our findings suggest that senotherapy offers a promising approach to preserving periodontal health,” Dr Sahingur said in a press release. “Periodontitis is more than a bacterial infection—it’s driven by immune and metabolic dysfunction, cellular ageing and inflammation. By targeting inflammation and senescent cells, we may disrupt the chronic disease cycle and unlock new preventive and therapeutic possibilities for oral and systemic health.”

The study tested a combination therapy using dasatinib, a drug that aids in the elimination of senescent cells by inhibiting enzymes crucial for their survival, and quercetin, a natural flavonoid widely available as an over-the-counter supplement. This combination has previously been shown to reduce senescent cell burden and associated markers in the context of other diseases.

In vitro experiments involved exposing human gingival keratinocytes to periodontitis-associated bacteria, inducing cellular changes associated with senescence. Treatment with dasatinib and quercetin significantly reduced markers of senescence and associated periodontal inflammation and bone loss. Similar results were seen in vivo, where gingival tissue in animal models showed a reduction in senescence and inflammation, restoring tissue profiles to those seen in younger, healthy controls. Notably, the treatment also helped prevent alveolar bone loss, indicating a potential role in preserving the structural integrity of the periodontium.

“These results are consistent with our previous studies and a growing body of research that shows the powerful role of natural compounds, like quercetin, in promoting oral and systemic health,” Dr Sahingur noted.

The research team now plans to initiate early-stage clinical trials to evaluate the effects of quercetin on clinical and biological markers in patients with periodontitis. Future trials may also examine low-dose, intermittent dasatinib—currently approved for use in the treatment of leukaemia—to assess its safety and efficacy in a periodontal setting.

“Our hope is that these initial clinical trials will provide proof of concept for leveraging the therapeutic potential of natural products—either as stand-alone agents or in combination regimens—as host modulatory strategies to enhance clinical outcomes in the management of periodontitis,” Dr Sahingur said. “If successful, this could lay the foundation for more targeted and effective treatments and delivery options, particularly for patients at high risk of severe periodontal diseases, such as the elderly, diabetics and immunocompromised.”

The study, titled “Dasatinib and quercetin limit gingival senescence, inflammation, and bone loss”, was published in the April 2025 issue of the Journal of Dental Research.