Researchers find a switch that reverses age and diabetes-related inflammation

Researchers have discovered a molecular switch that can stop inflammation related to aging and diabetes.

The results of a study that focused on the NLRP3 inflammasome and the molecular machine SIRT2 that can deactivate the inflammatory pathway were published online in Cell Metabolism on Feb. 6, and in print on March 3.

Study authors included MIng He, Hou-Hsien Chaing, Hanzhi Luo, Zhifang Zheng, Qi Quao, Li Wang, Mingdiean Tan, Rika Ohkubo, Wei-Chieh Mu, Shimin Zhao, Hao Wu., and Danica Chen.

Aging and overnutrition can activate the NLRP3 inflammasome producing inflammatory cytokines leading to development of low-grade inflammation. He et al. looked at the interface of the immune system and metabolism to understand if this could be reversed.  

He and the research team found that the NLRP3 inflammasome can be switched on and off by the process of adding or removing an acetyl group to the inflammasome complex. 

“Here, we show that NLRP3, a pattern recognition receptor, is modified by acetylation in macrophages and is deacetylated by SIRT2, an NAD+-dependent deacetylase and a metabolic sensor,” they wrote in the study. 

The research group developed a cell-based system modeling the inflammation that occurs as part of aging and used a co-culture system that simulated the inflammation from insulin resistance that occurs during aging.  By increasing the amount of SIRT2 in this experimental system and by modifying the inflammasome where modification takes place the researchers were able to reverse low-grade inflammation.

Although further validation is required and technological advancements will be necessary before this can be used in the clinic, this research is a key step in the advancement of the current understanding of low-grade inflammation.  It offers hope for people suffering from Type 2 diabetes or other aging-associated sources of inflammation. One day doctors may be able to modulate this molecular switch in humans and reverse the impact of overnutrition and aging.