Switching off aging and inflammation

A recent study from the University of California, Berkeley suggests there may be new ways to reverse current age-related conditions. These findings could have significant implications for rampant age-related conditions such as Alzheimer’s, Parkinson’s, diabetes, and even cancer.

Leading the study is senior author Danica Chen, Associate Professor of Metabolic Biology, Nutritional Sciences, and Toxicology at UC Berkeley. Her team first shows that the NLRP3 inflammasome, a large collection of proteins in charge of launching inflammatory responses to bodily threats, could be ‘switched off’ by a molecule removal process named deacetylation. Chen suggests that because overactivation of this inflammasome has been linked to conditions such as multiple sclerosis, cancer, and dementia, drugs that involve deacetylating could have practical applications in their treatment.

“This acetylation can serve as a switch,” Chen said in a UC Berkeley press release. “So, when it is acetylated, this inflammasome is on. When it is deacetylated, the inflammasome is off.”

Chen and her team found that a protein, called SIRT2, is capable of deacetylating the NLRP3 protein complex. By doing tests on mice and cells called macrophages, they found that mice that were bred without SIRT2 showed more inflammation at a younger age when compared to the control group. They were also shown to have higher insulin resistance, which is seen in individuals with type II diabetes and metabolic syndrome.

The team studied older mice with immune systems that had been destroyed by radiation. The researchers gave the mice blood stem cells that produced either the deacetylated or acetylated version of the NLRP3 inflammasome. The mice that produced the deacetylated version of the inflammasome had improved insulin resistance after six weeks, which has implications for reversing the course of metabolic disease.

“I think this finding has very important implications in treating major human chronic diseases,” Chen explained. “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 drug development for aging-related diseases.”

This research has important implications for those suffering from or at risk of cancer, Alzheimer’s, and diabetes, which are currently among the leading causes of death in the U.S. No current cure exists for these diseases. For instance, Alzheimer’s only has medicine to delay, not cure, the degenerative symptoms of memory loss. This is done mainly through cholinesterase inhibitors, which prevents the breakdown of chemical messengers involved in learning and memory.

Chen seeks to continue her research in inflammation. “In the past, we showed that aged stem cells can be rejuvenated. Now, we are asking: to what extent can aging be reversed?” said Chen in a press release.