Liver Inflammation Contributes to Brain Inflammation

Chronic, unresolved inflammation is a feature of aging. Constant inflammatory signaling is disruptive to tissue structure and function, and contributes to the onset and progression of all of the common, ultimately fatal age-related conditions. Inflammatory signal molecules generated in one organ will circulate throughout the body to provoke inflammation in other organs. This is the one of the many ways in which any one localized point of failure or excessive amount of age-related cell and tissue damage will tend to drag down the rest of the body.

As people age, the liver is among several organs that experience chronic, low-grade inflammation, a state that keeps the immune system activated even though there is no threat. Cells that die through necroptosis burst and release substances that lead to inflammation. Using an aging mouse model, researchers demonstrated the damaging effects of necroptosis in the liver, as well as the reduction of those effects when necroptosis was blocked. They also found that activating necroptosis in the liver increased liver inflammation and, surprisingly, increased brain inflammation, which affected the ability of mice to build nests, a possible sign of cognitive impairment.

"We hypothesize that when liver necroptosis is activated, the liver secretes toxic or inflammatory molecules that enter the bloodstream and cross the blood-brain barrier, where they cause inflammation in the brain. This type of organ crosstalk is becoming very important in research. Usually, when we study a disease condition, we focus on one organ, but when we do that, we miss the systemic effect. What we have found in our mice studies so far matches what is reported for patients - that people with liver diseases have high inflammation in the liver and also have cognitive issues. Our key question is what is causing this increase in inflammation in aging? It is important that we advance our knowledge in this area because it is critical that we develop new ways to treat these diseases."

Link: https://www.ouhsc.edu/News/details/organ-crosstalk-extends-harms-of-inflammation-from-liver-to-brain

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