Aging Cells & Diabetes: New Treatment Hope?

The aging of the body is not only reduced to a slow and inevitable degradation of the tissues, but also involves the accumulation of cells that no longer function normally and can disturb the metabolic balance.

Researchers are increasingly exploring whether removing these “aged” (senescent) cells could become a therapeutic strategy for age-related conditions such as type 2 diabetes.

A preclinical study by researchers at Cedars-Sinai Medical Center in Los Angeles suggests that senescent cells in the walls of blood vessels play an important role in the development of age-related metabolic dysfunctions, including insulin resistance and diabetes, and their elimination can significantly improve glycemic control.

What are “zombie” cells?

Senescent cells, sometimes called “zombie cells” in the scientific literature, are cells that, following stress or injuries, stop dividing permanently, but remain in the tissues. In certain contexts they can be useful, for example in wound healing, but as they accumulate with age, they release a series of pro-inflammatory molecules and signaling factors – the so-called senescence-associated secretory phenotype (SASP) – that promote chronic inflammation and impair normal organ function.

In the new study, published in the journal Cell Metabolism on November 20, the Cedars Sinai team specifically analyzed endothelial cells, which line the inside of blood vessels and are essential for the functioning of most organs.

The researchers induced obesity in mice through a high-fat diet, which increased the number of senescent endothelial cells marked by the p16 protein, then selectively eliminated this population of cells. After eliminating p16+ cells from the endothelium, the animals showed reduced inflammation in the adipose tissue, decreased fat mass, improved glucose tolerance and a global improvement in metabolic dysfunction.

In another experiment, the transplantation of senescent endothelial cells into lean mice with normal metabolism caused an increase in blood sugar and the establishment of insulin resistance, suggesting that these cells are not just a “marker” of aging, but an active factor that can trigger metabolic disorders.

Fisetin as possibly senolytic

As a possible proof of therapeutic principle, the team used fisetin – a natural flavonoid, a type of polyphenol, which is found in many fruits and vegetables, a compound with senolytic properties – substances capable of selectively eliminating senescent cells -, observing the improvement of glucose tolerance and the reduction of the number of senescent cells both in mice and in human tissue samples evaluated in the laboratory.

The authors point out, however, that fisetin and other senolytics are still being researched for this indication and are not currently approved for the treatment of diabetes in humans.

According to the researchers, the fact that the vascular endothelium influences metabolism in numerous tissues makes it a potentially attractive target for anti-aging and anti-metabolic interventions.

According to experts, targeting vascular senescence could, in principle, simultaneously modify several processes involved in aging and associated diseases.

Although the results are promising, the study has the inherent limitations of preclinical research, being carried out on animal models, the precise mechanisms by which senescent endothelial cells deregulate metabolism in humans are to be clarified.

The next step for the Cedars Sinai team will be to test the safety and effectiveness of senolytic therapies or more specific methods of eliminating vascular senescent cells in human clinical trials.

If these results are confirmed, they could pave the way to new treatments for type 2 diabetes and other age-related metabolic diseases by reducing chronic inflammation and restoring insulin sensitivity.