Drugs that selectively kill senescent cells may work for healthy older women, but they’re not a “cure-all” treatment, Mayo Clinic researchers have found. Specifically, these drugs may only be effective in people with high numbers of senescent cells, according to the results of a study published July 2. Nature Medicine.
Senescent cells are cells in the body that become dysfunctional and dormant. These cells, also known as “zombie cells,” cannot divide but can contribute to the chronic inflammation and tissue dysfunction associated with aging and chronic disease. Senescent cell removal drugs remove senescent cells from tissues.
In a 20-week, phase 2 randomized controlled trial, 60 healthy postmenopausal women received an intermittent senolytic combination of FDA-approved dasatinib and quercetin, a natural substance found in some foods. This is the first randomized controlled trial of intermittent senolytic treatment in healthy older women, and the researchers used bone metabolism as a measure of efficacy.
The researchers found that while the combination, known as D+Q, had beneficial effects on bone formation, it did not reduce bone resorption, or the breakdown and removal of bone tissue. What’s more, D+Q worked primarily in people with a proven high number of senescent cells. This group saw a more robust increase in bone formation, a decrease in bone resorption, and increased bone density in the wrist.
“Our findings argue against what many people already do: use over-the-counter products like quercetin and related compounds like fisetin that may have anti-aging properties,” says Sandeep Khosla, MD, an endocrinologist at the Mayo Clinic in Rochester, Minnesota, and senior author of the paper. “They’re using them as anti-aging drugs without knowing whether they’re targeting high enough senescent cells to be effective, or what the dosage and dosing regimen would need to be to be effective and safe.”
Dr. Khosla says further research is needed to more precisely identify people who may benefit from senolytic therapies and to develop more specific and powerful senolytic drugs that could work for a larger population of people. People who experience “accelerated aging,” such as cancer survivors after chemotherapy or patients with progeria syndrome, may have increased numbers of senescent cells.
Beyond their application in aging, anti-aging drugs may also be effective in treating specific diseases, such as idiopathic pulmonary fibrosis, dementia, diabetes and heart disease, Dr. Khosla says, but these drugs would need to be customized for potency and the amount of senescent cells in the diseased tissue.
