Dasatinib and Quercetin Limit Gingival Senescence, Inflammation, and Bone Loss

Area of Science:

• Gerontology and Periodontology
• Cellular senescence and aging research
• Microbiome-host interactions in oral health

Background:

• Cellular senescence is a key aging hallmark and driver of chronic diseases, including periodontal disease.
• Senescent cells and their secreted factors (SASP) contribute to periodontal pathogenesis.
• Senotherapeutics, like dasatinib and quercetin (DQ), target senescent cells to improve healthspan.

Purpose of the Study:

• To investigate the efficacy of dasatinib and quercetin (DQ) in mitigating periodontal tissue senescence and SASP.
• To evaluate DQ's impact on periodontal health in preclinical models of aging and bacterial challenge.

Main Methods:

• In vitro: Human gingival keratinocytes exposed to *Fusobacterium nucleatum* were treated with DQ.
• Assessed senescence markers (p16, SA-β-galactosidase, lamin-B1) and SASP factors (IL-8, MMP-1, MMP-3).
• In vivo: Aged mice received oral DQ to assess effects on gingival senescence, SASP, and periodontal bone loss.

Main Results:

• DQ treatment reduced senescence markers and SASP factors in gingival keratinocytes challenged by periodontal bacteria.
• Oral DQ administration decreased senescent cell burden and SASP in gingival tissues of aged mice.
• DQ treatment significantly reduced naturally progressing periodontal bone loss in aged mice.

Conclusions:

• Targeting gingival senescence and the senescence-associated secretome with DQ is a viable strategy for improving periodontal health.
• DQ demonstrates potential as a senotherapeutic intervention for age-related periodontal diseases and bone loss.
• Findings support further translational studies for DQ in vulnerable populations at risk for periodontal disease.