FEB 09, 2020 1:01 PM PST

Switching Inflammation Off at the Molecular Level

WRITTEN BY: Carmen Leitch

While chronic inflammation is a natural result of getting old and experiencing stress and toxin exposure, it has been theorized to be the basis for a wide variety of chronic diseases. Scientists have now found a molecule that acts as a kind of switch that regulates the biological mechanisms that underlie chronic inflammation. The findings, which were reported in Cell Metabolism, may offer insight into treatments for many conditions including cancer, diabetes, and Alzheimer's.

Image credit: Pexels

"My lab is very interested in understanding the reversibility of aging," said the senior study author Danica Chen, an associate professor of metabolic biology, nutritional sciences and toxicology at the University of California 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."

A protein complex called the NLRP3 inflammasome helps sense and respond to potential threats against the body. Overactivation of this complex has been associated with chronic diseases including dementia, diabetes and cancer.

Chen's team has determined that this complex can be inactivated by deacetylating or deleting a chemical group from the NLRP3 inflammasome. It may be possible to treat age-related chronic inflammation and the diseases that come with it by using drugs that aim to deacetylate or turn off the NLRP3 inflammasome.

"This acetylation can serve as a switch," Chen explained. "So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off."

Investigating further, the researchers learned that a protein called SIRT2 normally acts to deacetylate the NLRP3 inflammasome. Using a mouse model, the scientists genetically deleted the SIRT2 protein, and found that the mice had a greater degree of inflammation at the age of two than normal mice. The inflamed mice also had higher resistance to insulin, which is connected to metabolic diseases.

In another mouse model, the immune systems of older mice were knocked out with radiation and then replenished with blood stem cells. One group was given stem cells that were made to generate a deacetylated NLRP3 inflammasome, the other group got acetylated NLRP3 inflammasome. After six weeks, insulin resistance went down in the mice that received the inactivated or deacetylated version. It may be possible, therefore, to reverse the progression of inflammation-related 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."

Sources: Science Daily via UC Berkeley, Cell Metabolism

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 11, 2020
Genetics & Genomics
A Better Understanding of Telomere Length Throughout the Body
SEP 11, 2020
A Better Understanding of Telomere Length Throughout the Body
Telomeres cap the ends of chromosomes. They work to protect the chromosomes from degradation, and are known to get short ...
OCT 09, 2020
Cell & Molecular Biology
Proteins Have an Orientation in Plant Cells
OCT 09, 2020
Proteins Have an Orientation in Plant Cells
Just like animals, plants are made of cells that are full of proteins. The proteins in plant cells are often only found ...
OCT 19, 2020
Cell & Molecular Biology
Mapping the Human Proteome
OCT 19, 2020
Mapping the Human Proteome
To learn more about biology and medicine, researchers have used advances in molecular techniques and computational biolo ...
OCT 25, 2020
Cell & Molecular Biology
Revealing More About the Genetics of Ewing Sarcoma
OCT 25, 2020
Revealing More About the Genetics of Ewing Sarcoma
Ewing sarcoma is a rare kind of cancer that tends to impact young people and occurs in bones or the tissue around them. ...
NOV 05, 2020
Clinical & Molecular DX
Digging DEEP into Metabolomic Space
NOV 05, 2020
Digging DEEP into Metabolomic Space
Metabolomics is an umbrella term encompassing lipidomics and the study of smaller polar metabolites.  As such, more ...
NOV 12, 2020
Genetics & Genomics
Liposomes Potentially Safer Alternative to Viruses for CRISPR Delivery
NOV 12, 2020
Liposomes Potentially Safer Alternative to Viruses for CRISPR Delivery
To repair disease-causing errors in the genome, gene editing reagents like those used in CRISPR-Cas9 first have to reach ...
Loading Comments...