The Emerging Role of Accelerated Cellular Senescence in Periodontitis

Abstract

Accelerated cellular senescence may be a crucial process for periodontitis progression because it integrates the damaging effects of major periodontitis risk factors. Cellular senescence is a manifestation of aging at the cellular level. However, recent technological advances have shown that healthy young cells continuously exposed to sublethal oxidative stress undergo accelerated senescence. Although accumulation of senescent cells is normal in aged tissues, persistent bacterial infection, chronic inflammation, diabetes, and smoking promote the early onset of senescence by causing DNA damage. As a result, the premature accumulation of senescent cells not only increases tissue destruction but also limits regeneration. Senescent cells are a source of chronic inflammation, and once they start to accumulate, a “two-source” periodontal inflammation results from both bacteria-triggered and senescence-associated inflammation. Senescent cells also transmit senescence to nearby healthy cells, generating a vicious cycle that extends the affected area over time. Since senescent cells Accumulate, Limit regeneration, Transmit senescence, Exacerbate inflammation, and Remodel tissues, the acronym ALTER is suggested to summarize key senescence-associated features implicated in tissue deterioration. Given that different homeostatic mechanisms are disrupted during the transition of gingivitis to periodontitis and that the network of senescence-associated events disrupts local homeostasis, accelerated activation of cellular senescence could be a central underlying mechanism for periodontitis progression. In this review, the emerging contribution of premature DNA damage-driven cellular senescence in periodontitis is discussed. This novel knowledge is particularly important to better understand the host contribution in periodontal destruction and will help to develop new therapeutic strategies.