The Interplay Between Genotoxic Stress And STING Activation In Cellular Senescence And Inflammatory Responses
Our cells are constantly exposed to various stressors that can damage their DNA, a process known as genotoxic stress. When DNA is damaged, it can sometimes escape the cell’s nucleus and appear in the cytoplasm, where it doesn’t belong. This misplaced DNA acts as a danger signal, alerting a crucial cellular defense system.
This defense system involves a protein called cGAS, which detects the abnormal DNA and then activates another protein called STING. Once activated, the STING pathway triggers a cascade of events that lead to two significant cellular responses: cellular senescence and inflammation. Cellular senescence is essentially a state of irreversible growth arrest, often referred to as cellular aging, where cells stop dividing but remain metabolically active. These senescent cells can then release inflammatory molecules, contributing to chronic inflammation in tissues.
Understanding this connection between DNA damage, STING activation, cellular aging, and inflammation is vital. The research highlights that STING activation can promote cellular aging and programmed cell death, and also contribute to inflammation, often through signaling pathways like NF-κB. This discovery opens up new avenues for potential therapies targeting the STING pathway to combat age-related diseases and chronic inflammatory conditions by modulating how cells respond to DNA damage.
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