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:
Aging-related degeneration
- Diabetes Drugs Linked With Lower Risks of Open-Angle Glaucoma, AMD
New findings from a prospective cohort study outline associations between diabetes medications and common eye conditions, such as open-angle glaucoma and age-related macular degeneration (AMD).
- Springer Honoree explores age-related macular degeneration at annual lecture
Age-related macular degeneration was the topic at the UAB School of Optometry’s annual Springer Lecture, presented by the 2017 Springer Award Honoree, Christine Curcio, Ph.D., professor at the UAB ...
- Dried goji berries may provide protection against age-related vision loss
Regularly eating a small serving of dried goji berries may provide protection against age-related macular degeneration, the leading cause of vision loss in seniors. The researchers found that 13 ...
- Arizona surgeon first to administer new gene therapy to combat macular degeneration
Dr. Mark Barakat is the first surgeon in the state to administer the new gene therapy for people who suffer from the disease.
- A step closer to treatment for the most common form of blindness
Scientists at The University of Manchester have taken an important step towards finding a treatment for age-related macular degeneration (AMD), the most common form of adult blindness in the developed ...
Go deeper with Google Headlines on:
Aging-related degeneration
Go deeper with Bing News on:
Chronic inflammation
- How chronic inflammation spreads
During the brutal wildfire season last year, California's Dixie fire laid waste to more than 192,000 acres. The Bootleg/Log fire in Oregon was even larger, covering more than 400,000 acres. Like those ...
- Your Best Life: Foods to fight inflammation
Heart disease, diabetes, cancer, and even arthritis; there are a lot of diseases linked to chronic inflammation. Now researchers say the best medicine may ...
- How Inflammation Affects Your Health
The word "inflammation" might conjure up images of a swollen ankle after some missteps on a long hike. But inflammation has also emerged as a key factor in serious diseases, such as cardiovascular ...
- Healthy diet helps obese people with chronic inflammation and skin wound healing
Why do chronic inflammatory conditions like psoriasis occur more in people with obesity? Experts at Leipzig University Hospital have investigated which factors negatively influence inflammatory ...
- 'Growing end' of inflammation discovered
Redness, swelling and pain are signs of inflammation. It serves to protect the body from pathogens and foreign substances. Researchers from the Universities of Bonn and Cologne were able to show that ...