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Review
. 2020 Oct 9;21(20):7441.
doi: 10.3390/ijms21207441.

Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?

Ruben Aquino-Martinez  1 , Sundeep Khosla  1   2 , Joshua N Farr  1   2 , David G Monroe  1   2
Affiliations
Review

Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?

Ruben Aquino-Martinez et al. Int J Mol Sci. .

Abstract

The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction.

Keywords: DNA damage; bacterial infection; cellular senescence; immune response; inflammation; molecular mechanism; pathogenesis; periodontal disease; periodontitis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Telomere dependent and independent factors contribute to the onset of cellular senescence. Telomeres gradually shorten as a result of cell division eventually leading to cellular senescence, a phenotype characterized by permanent growth arrest. Although mitotic cell division is the main cause of telomere shortening, this process can be affected or accelerated when cells are exposed to oxidative stress or genotoxic agents. Indeed, unrelated factors, such as radiation, H2O2, or certain Gram-negative bacteria products, can induce premature senescence.
Figure 2
Figure 2
Interconnected factors that may contribute to the accumulation of senescent cells in periodontal microenvironment. Persistent Gram-negative bacterial infection causes chronic inflammation and DNA damage in host cells. Chronic inflammation itself induces oxidative stress in healthy cells. Downregulated local immune response and immune surveillance. Constant renewal of damaged periodontal tissues leads to stem cell exhaustion.
Figure 3
Figure 3
Potential mechanism by which senescent cells aggravate periodontal tissue deterioration. Cells that survive persistent DNA damage acquire a senescent phenotype, which is characterized by the hypersecretion of key proinflammatory cytokines. DNA damage-driven senescence is a crucial intermediate mechanism between DNA damage and host immune activation. Released factors by these dysfunctional cells could aggravate the initial immune reaction against pathogenic bacteria. Thus, gradual accumulation of senescent cells in periodontal tissues during lifetime could contribute to the progression of periodontal tissue deterioration.
Figure 4
Figure 4
Senescent cells in periodontal tissues are an additional source of proinflammatory factors. Senescence-associated factors can potentially interact and exacerbate bacteria-induced chronic inflammation. NF-κB activation plays an important role in bacterial recognition and nuclear DNA damage signaling.
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