Inflammation Switch
Chronic inflammation that occurs in old age, against the background of prolonged stress or as a result of the action of toxins from the environment, keeps the body's immune system in a state of overload and can contribute to the development of a number of diseases, from Alzheimer's and Parkinson's disease to diabetes and cancer.
Researchers from the University of California at Berkeley have studied a molecular switch that controls the immune mechanism responsible for chronic inflammation in the body. The research may lead to the creation of new ways that can stop or even reverse many of the age-related conditions and chronic diseases.
Researchers have shown that a bulky set of NLRP3 inflammasomes ("inflammatory bodies") responsible for perceiving potential threats to the body and triggering an inflammatory response can be disabled by deacetylation.
Hyperactivation of NLRP3-inflamosomes is associated with many chronic conditions, including multiple sclerosis, cancer, diabetes and dementia. Tests have shown that medications aimed at deacetylating or disabling NLRP3 can prevent or cure these diseases and possibly age-related degeneration in general.
As the researchers have shown, acetylation of NLRP3 can serve as a switch that triggers inflammation, and deacetylation extinguishes it.
After studying mice and human macrophages, the team found that the SIRT2 protein is responsible for deacetylation by NLRP3 inflammasome. Mice with a mutation that prevented the production of SIRT2 had more signs of inflammation at the age of two years than their normal peers. These mice also showed more pronounced insulin resistance, turning into type 2 diabetes mellitus and metabolic syndrome.
To understand the role of deacetylation in older mice, the immune system was destroyed by radiation, and then restored with blood stem cells that produced either a deacetylated or acetylated version of the NLRP3 inflammasome. Individuals who received the deacetylated – "off" version improved their response to insulin after six weeks. This means that disabling the immune mechanism can actually change the course of metabolic disease.
The study is very important for the development of methods for the treatment of major chronic human diseases, as well as conditions associated with the aging process.
Article M.He et al. An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance is published in the journal Cell Metabolism.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Berkeley News: Molecular 'switch' reverses chronic inflammation and aging.