Killing 'Zombie' Blood-Vessel Cells Restores Glucose Control in Mice — Early Study Suggests New Diabetes Strategy

A new study finds that senescent — or so-called “zombie” — cells that line blood vessels may drive metabolic dysfunction with age, and that selectively eliminating these cells can improve glucose control in mice. The research points to blood-vessel endothelial cells as a unifying target that could influence whole-body metabolism and may inform future treatments for age-related metabolic disease.

What are senescent cells? Cells become senescent in response to stress: they permanently stop dividing but remain metabolically active in tissues. While senescence can serve beneficial roles, such as aiding wound healing, senescent cells also accumulate with age and secrete inflammatory molecules collectively called the Senescence-Associated Secretory Phenotype (SASP). SASP factors can disrupt normal cell and tissue function and are increasingly implicated in age-related diseases, including metabolic disorders.

Study design and key findings

Researchers focused on endothelial cells, the cells that form the inner lining of blood vessels and influence organ metabolism. In one experiment, mice fed a high-fat diet (to induce weight gain and cellular senescence) underwent selective removal of senescent endothelial cells. The treated mice showed reduced fat mass, better blood-glucose control and overall improvement in metabolic function.

In a complementary experiment, the team induced senescence in endothelial cells using radiation and then transplanted those senescent cells into lean mice. The recipient mice developed higher blood glucose and insulin resistance, consistent with a causal role for senescent vascular cells in metabolic dysfunction.

Senolytic treatment with fisetin

The researchers then treated both experimental groups with fisetin, a natural flavonoid the team had previously identified as having senolytic activity (meaning it can selectively clear senescent cells). Fisetin treatment reduced the number of senescent endothelial cells and improved glucose tolerance in the mouse models. The team also treated vascular tissue samples from six adults with obesity (in their 40s and 50s) and observed a similar reduction in senescent endothelial cells ex vivo.

Expert perspective and implications

“By finding a unifying target, such as blood vessels, you open up the possibility that you might be able to, at the same time, target very different aspects of aging,” said Dr. Christina Aguayo-Mazzucato, an assistant professor of medicine at Harvard Medical School, who was not involved in the study.

The findings suggest that targeting senescent vascular cells could be a promising strategy to improve metabolic health and perhaps affect multiple age-related conditions. Because blood vessels are present throughout the body, interventions aimed at senescent endothelial cells might influence diverse tissues and disease processes.

Limitations and next steps

These results are preclinical. While the mouse experiments and human tissue assays are encouraging, clinical trials are needed to determine whether senescent endothelial cells have the same effects in living humans and whether senolytic treatments like fisetin are safe and effective for metabolic disease. The researchers emphasize caution: translating findings from mice and ex vivo human tissues into approved therapies requires rigorous testing.

Conclusion

The study highlights senescent endothelial cells as contributors to metabolic dysfunction in mice and identifies senolytic clearance — using compounds such as fisetin — as a potential avenue to restore metabolic balance. Further research, including human clinical trials, is required before this approach can be recommended for people.

Study and credits: Lead author Dr. Mayasoshi Suda and co-author Dr. Nicolas Musi (Cedars-Sinai Medical Center); published in Cell Metabolism. This article is informational and does not constitute medical advice.