IADR Abstract Archives
Deciphering oral tissue aging: The role of TMPRSS11a in the accumulation of senescent cells
Objectives: The life expectancy has increased exponentially. Along with this, there has been an epidemiological transition from infectious to chronic non-communicable diseases associated with aging. One of the hallmarks of aging is cellular senescence, which has been associated with various aging-related pathologies due to its accumulation in tissues by a mechanism that is still unknown. Particularly the effect of senescent cells in various tissues has been described; however, this phenomenon is unknown in gingival tissue. Results from our laboratory indicate that a anchored-membrane protease, TMPRSS11a, induces senescence by increasing its expression is increased in gingival tissue from aged donors.
In gingival tissue little is known about induction of cellular senescence when exposed to bacterial noxa and pro-inflammatory environments and how the accumulation of these cells affects the loss of homeostasis and tissue function.
Methods: To determine how various sublethal stimuli induce senescence and alter the recognition of senescent cells by the immune system, using primary gingival fibroblasts exposed to sublethal doses of LPS, TNF-α and H2O2, we evaluated by cell biology and biochemistry techniques markers associated with senescence and recognition ligands for senescent cells by the immune system.
Results: We found that stimulation for 7 days with these stimuli increased markers of SAHF, DDR and cell cycle arrest, as well as increased levels of TMPRSS11a. We also found alterations in the levels of recognition ligands such as CD112, CD155, MICA/B and HLA-C.
Conclusions: Our findings indicate that bacterial noxa or proinflammatory environments to which oral tissue is subjected effectively induce senescence in gingival fibroblasts and that these alter their recognition molecules favoring their accumulation in tissue and affecting their homeostasis. This knowledge allows us to develop tools or therapies that target these mechanisms for the application of senolytic or senostatic strategies and thus delay or reverse oral pathologies associated with aging.
In gingival tissue little is known about induction of cellular senescence when exposed to bacterial noxa and pro-inflammatory environments and how the accumulation of these cells affects the loss of homeostasis and tissue function.
Methods: To determine how various sublethal stimuli induce senescence and alter the recognition of senescent cells by the immune system, using primary gingival fibroblasts exposed to sublethal doses of LPS, TNF-α and H2O2, we evaluated by cell biology and biochemistry techniques markers associated with senescence and recognition ligands for senescent cells by the immune system.
Results: We found that stimulation for 7 days with these stimuli increased markers of SAHF, DDR and cell cycle arrest, as well as increased levels of TMPRSS11a. We also found alterations in the levels of recognition ligands such as CD112, CD155, MICA/B and HLA-C.
Conclusions: Our findings indicate that bacterial noxa or proinflammatory environments to which oral tissue is subjected effectively induce senescence in gingival fibroblasts and that these alter their recognition molecules favoring their accumulation in tissue and affecting their homeostasis. This knowledge allows us to develop tools or therapies that target these mechanisms for the application of senolytic or senostatic strategies and thus delay or reverse oral pathologies associated with aging.