Experimental drugs clear zombie-like cells and apply brakes to diabetes

Zombie-like cells that have stopped dividing in the human body and accumulate as we age, known as senescent cells, continue to find themselves at the center of all kinds of medical breakthroughs. A new study has explored how these damaged, lingering cells can negatively influence the behavior of fat cells, and demonstrated how their removal can alleviate diabetes symptoms in obese mice.

Among the ways senescent cells can hamper the activity of neighboring, healthy cells, is by altering the way they process sugars and proteins, which can lead to problems with metabolism. This new study carried out by scientists at the University of Connecticut sought to shine new light on the role these zombie cells play in type 2 diabetes, a metabolic condition affecting around 34 million people in the US.

To do so, the scientists turned their focus to insulin resistance, a major risk factor for type 2 diabetes whereby the body’s cells don’t respond well to insulin and prevent the uptake of glucose, causing it to build up in the blood instead. Insulin resistance is associated with obesity and present in most people with diabetes, so the scientists used obese mice as a model to shed new light on this relationship.

The experiments revealed a population of senescent cells had accumulated in the fat tissue of the obese mice, and showed that intermittently clearing them away prevented and alleviated insulin resistance. The team also tested the ability of experimental senolytic drugs dasatinib and quercetin to eliminate the senescent cells in human tissue in the lab, with great success. Notably, this donated tissue from obese individuals was then transplanted to mice, where it triggered insulin resistance. The scientists were then able to use the same drug cocktail to almost eliminate this effect.

“These drugs can make human fat healthy, and that could be great,” says study author Ming Xu. “The results were very impressive and cleared the route for potential clinical trials.”

The scientists say the population of senescent cells at the heart of the study express high levels of a cyclin-dependent kinase inhibitor called p21. Where previous research in this area had focused on different cell markers, the scientists say that clearing away the cells expressing high levels of p21 produced such strong effects in alleviating the effects of diabetes that the technique warrants more attention.

“Although these preclinical results were very promising, large-scale clinical trials are absolutely critical to examine the efficacy and safety of these drugs in humans before clinical use,” says Xu.

The research was published in the journal Cell Metabolism

Source: University of Connecticut

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