The NLRP3 receptor protein is responsible for detecting potential pathogens in the body and launching an immune response. (Image by MLGProGamer123 via Wikimedia Commons)
Chronic inflammation, which results when old age, stress or environmental toxins keep the body’s immune system in overdrive, can contribute to a variety of devastating diseases, from Alzheimer’s and Parkinson’s to diabetes and cancer.
Now, scientists at the University of California, Berkeley, have identified a molecular “switch” that controls the immune machinery responsible for chronic inflammation in the body. The finding, which appears online Feb. 6 in the journal Cell Metabolism, could lead to new ways to halt or even reverse many of these age-related conditions.
“My lab is very interested in understanding the reversibility of aging,” said senior author Danica Chen, associate professor of metabolic biology, nutritional sciences and toxicology at UC Berkeley. “In the past, we showed that aged stem cells can be rejuvenated. Now, we are asking: to what extent can aging be reversed? And we are doing that by looking at physiological conditions, like inflammation and insulin resistance, that have been associated with aging-related degeneration and diseases.”
In the study, Chen and her team show that a bulky collection of immune proteins called the NLRP3 inflammasome — responsible for sensing potential threats to the body and launching an inflammation response — can be essentially switched off by removing a small bit of molecular matter in a process called deacetylation.
Overactivation of the NLRP3 inflammasome has been linked to a variety of chronic conditions, including multiple sclerosis, cancer, diabetes and dementia. Chen’s results suggest that drugs targeted toward deacetylating, or switching off, this NLRP3 inflammasome might help prevent or treat these conditions and possibly age-related degeneration in general.
“This acetylation can serve as a switch,” Chen said. “So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off.”
By studying mice and immune cells called macrophages, the team found that a protein called SIRT2 is responsible for deacetylating the NLRP3 inflammasome. Mice that were bred with a genetic mutation that prevented them from producing SIRT2 showed more signs of inflammation at the ripe old age of two than their normal counterparts. These mice also exhibited higher insulin resistance, a condition associated with type 2 diabetes and metabolic syndrome.
The team also studied older mice whose immune systems had been destroyed with radiation and then reconstituted with blood stem cells that produced either the deacetylated or the acetylated version of the NLRP3 inflammasome. Those who were given the deacetylated, or “off,” version of the inflammasome had improved insulin resistance after six weeks, indicating that switching off this immune machinery might actually reverse the course of metabolic disease.
“I think this finding has very important implications in treating major human chronic diseases,” Chen said. “It’s also a timely question to ask, because in the past year, many promising Alzheimer’s disease trials ended in failure. One possible explanation is that treatment starts too late, and it has gone to the point of no return. So, I think it’s more urgent than ever to understand the reversibility of aging-related conditions and use that knowledge to aid a drug development for aging-related diseases.”
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
- Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategieson February 25, 2021 at 12:28 pm
Despite these multiple potential pathomechanisms, it is far from clear how exactly abnormal tau causes or contributes to neuronal dysfunction and degeneration ... and likely to take other medications ...
- See the world through others' eyes: 360-degree images reveal how iconic tourist spots look to people with ocular conditions including cataracts, glaucoma and tunnel visionon February 23, 2021 at 11:22 am
Users can see 'floaters' over the Sydney Opera House, experience the lights of Times Square dimmed by night blindness and view Dubai with colour deficiency.
- Revision Eye supplement Reviews - Does Revision 2.0 Eye Capsules Really Work - Review By DietCare Reviewson February 14, 2021 at 9:05 pm
The ReVision eye supplement works to reverse aging-related damage ... age-related cell degeneration. Thanks to this mechanism, one enjoys full recovery with long term effects.
- Chutes & Ladders—After Verastem pit stop, bluebird vet Neumann lands at Kiteon February 12, 2021 at 1:30 am
where she ran its clinical-stage program targeting aging biology as a new way to treat aging-related conditions. Release > Clinical-stage biotech Frequency Therapeutics has signed on Kevin Franck ...
- Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injuryon February 10, 2021 at 3:58 am
We then focus on the causative functions of AGEs that impact various aging-related diseases ... caspase-3 to enhance neuronal apoptosis and/or degeneration with elevated gliosis 110.
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammationon March 5, 2021 at 2:12 pm
Imbalance between proteases and their inhibitors plays a crucial role in the development of Inflammatory Bowel Diseases (IBD). Increased elastolytic activity is observed in the colon of patients ...
- Lipid, fatty acid, carnitine- and choline derivative profiles in rheumatoid arthritis outpatients with different degrees of periodontal inflammationon March 5, 2021 at 7:08 am
Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases with several pathogenic pathways in common. Evidence supports an association between the diseases, but the exact ...
- New molecular mechanisms identified in chronic skin inflammationon March 5, 2021 at 4:27 am
Frequently occurring chronic skin inflammation like in atopic dermatitis (AD or neurodermatitis) and psoriasis have different causes such as genetic predisposition, stress or allergens. These ...
- Suffering from chronic inflammation? Study finds new way to put brakes on excessive inflammationon March 4, 2021 at 11:31 pm
Are you suffering from chronic inflammation? RCSI researchers find a new way to halt excessive inflammation. Read on to know more.
- Researchers identify new molecular mechanisms in chronic skin inflammationon March 4, 2021 at 10:45 pm
Frequently occurring chronic skin inflammation like in atopic dermatitis (AD or neurodermatitis) and psoriasis have different causes such as genetic predisposition, stress or allergens.