Combination Therapy May Reduce Cardiovascular Disease

Long-term use of senolytic drugs to clear damaged cells from the body can help prevent heart disease.

The removal of senescent cells has the potential to help reduce cardiovascular disease, a recent study suggests.

"Cardiovascular disease remains the leading cause of death in our population today, and disability related to heart disease and stroke has a tremendous impact on our aging population," said co-corresponding study author James Kirkland, MD, PhD. "This is the first evidence that longer term use of senolytic drugs to clear these damaged cells from the body can have a preventative impact against vascular diseases."

Previously, the Mayo Clinic evaluated chronic removal of cells from genetically altered mice and how it can change or delay many different health conditions. By applying a short term treatment using drugs that remove the senescent cells, it can improve the function of the endothelial cells that line the blood vessels.

Senescent cells have been damaged and can no longer function as normal. These damaged cells remain in the body and add to frailty and other aging health conditions.

The study conducted by the Mayo Clinic, published in the Aging Cell, looked at functional and structural impacts the blood vessels might experience over time when combination drugs clear the senescent cells.

The combination of the drugs dasatinib and quercetin were given to 24-month-old mice orally over a 3 month period, following the initial 2 years. Researchers also had another set of mice with high cholesterol and were able to develop atherosclerotic plaques for 4 months, followed by treatment with the combination drugs for 2 months.

The results of the study showed that in naturally aged mice or in atherosclerotic mice, the clearing of senescent cells alleviated vascular dysfunction.

In mice with the high cholesterol, there was no reduction in the size of the plaques, however, it reduced calcification of plaques already in existence on the interior of vessel walls.

"Our finding that senolytic drugs can reduce cardiovascular calcification is very exciting, since blood vessels with calcified plaques are notoriously difficult to reduce in size, and patients with heart valve calcification currently do not have any treatment options other than surgery," said senior author Jordan Miller, PhD. "While more research is needed, our findings are encouraging that one day removal of senescent cells in humans may be used as a complementary therapy along with traditional management of risk factors to reduce surgery, disability, or death resulting from cardiovascular disease."