Activation Of Cgas-STING Signaling In Senescent Cells Promotes The Aging Process By Remodeling The Functions Of The Immune System
As we age, our bodies accumulate “senescent cells” – cells that have stopped dividing but remain active, often releasing substances that can be harmful. A key discovery reveals that a particular internal alarm system, known as the cGAS-STING pathway, plays a significant role in this process. This pathway gets triggered when double-stranded DNA, which normally resides safely inside the cell’s nucleus or mitochondria, leaks into the cell’s main fluid compartment (cytosol). This leakage acts as a danger signal, activating the cGAS-STING pathway.
Once activated in these senescent cells, this pathway doesn’t just sit there; it actively remodels the immune system. On one hand, it can spark inflammation by increasing the release of signaling molecules like cytokines and chemokines, which are small proteins that help cells communicate, and colony-stimulating factors, which promote the growth of blood cells. This can lead to changes in how blood cells are formed and even contribute to the shrinking of the thymus, an organ crucial for immune function, as we get older. It also activates inflammasomes, which are protein complexes that trigger inflammatory responses.
However, the cGAS-STING pathway also has a more complex role. It can contribute to resolving inflammation by attracting cells that suppress immune responses and by dampening the activity of certain immune cells called T helper 17 cells. Furthermore, it can boost the production of molecules that act as “brakes” on the immune system, such as PD-L1, potentially preventing the immune system from clearing out these problematic senescent cells. Ultimately, this pathway not only helps create senescent cells but also actively drives the aging process by altering the delicate balance and function of our immune defenses.
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