Innate Immune cGAS/STING Signaling is Both Necessary and Pathological

Chronic, unresolved inflammation is a feature of aging. When the immune system is constantly active in this way, the consequent altered cell behavior throughout the body becomes disruptive to tissue and organ function, harmful to the individual. Chronic inflammation accelerates the onset and progression of all of the common fatal age-related conditions. This unwanted inflammatory signaling arises from many different roots, including the growing presence of senescent cells, but also the interaction of innate immune sensors with other forms of age-related dysfunction. For example, damage-associated molecular patterns such as mislocalized fragments of mitochondrial DNA leaking from dysfunctional mitochondria into the cell cytosol can trigger cGAS/STING signaling. This mechanism evolved to detect the presence of bacterial DNA, and unfortunately runs awry with age. The challenge inherent in dampening age-related chronic inflammation is that, so far, it appears to use exactly the same pathways that are involved in the normal, necessary, short-term inflammatory response to injury, pathogens, potentially cancerous cells, and so forth. All of the approaches developed to date to suppress the overactivity of an immune system also suppress necessary functions, and that produces unpleasant long-term consequences. This is well established via the use of immunosuppressant drugs in patients with autoimmune disease. There was some hope that targeting aspects of cGAS/STING function woul...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs