Drugs that selectively eliminate senescent cells may offer benefits to some older women but are not universally effective, according to research from the Mayo Clinic. The study, published in Nature Medicine, indicates these drugs might only benefit individuals with a high number of senescent cells.
Senescent cells, often referred to as "zombie cells," are malfunctioning cells that become dormant and contribute to chronic inflammation and tissue dysfunction associated with aging and chronic diseases. Senolytic drugs aim to clear these cells from tissues.
The 20-week phase 2 randomized controlled trial involved 60 healthy postmenopausal women who intermittently received a combination of FDA-approved dasatinib and quercetin, known as D+Q. This trial is the first of its kind for intermittent senolytic treatment in healthy aging women, using bone metabolism as a marker for efficacy.
Researchers found that D+Q positively impacted bone formation but did not reduce bone resorption or the breakdown of bone tissue. The benefits were primarily observed in individuals with a high number of senescent cells, who experienced significant increases in bone formation, decreases in bone resorption, and increased bone mineral density at the wrist.
"Our findings argue against what many people are already doing — using commercial products like quercetin or related compounds like fisetin that may show some senolytic properties," says senior author Sundeep Khosla, M.D., an endocrinologist at Mayo Clinic in Rochester, Minnesota. "They're using them as anti-aging agents without knowing if they have high enough senescent cell numbers to benefit or what dose or dosing regimen is needed to be effective yet safe."
Dr. Khosla emphasizes the need for further research to identify individuals who could benefit from senolytic treatments and develop more specific and potent drugs. People experiencing "accelerated aging," such as cancer survivors post-chemotherapy or those with progeroid syndromes, may have higher numbers of senescent cells.
Beyond aging applications, senolytic drugs might also address diseases like idiopathic pulmonary fibrosis, dementia, diabetes, heart disease, among others. These treatments will likely need customization based on their potency and the quantity of senescent cells present in diseased tissues.
The study was supported by several National Institutes of Health grants: R21 AG065868, P01 AG062413, R01 AG 076515, R01 DK128552, R01 AG055529, R37 AG13925 and R33 AG61456.
Co-authors include Joshua Farr, Ph.D., Elizabeth Atkinson, Sara Achenbach, Tammie Volkman, Amanda Tweed, Stephanie Vos, Ming Ruan, Jad Sfeir M.D., Matthew Drake M.D., Ph.D., Dominik Saul M.D., Madison Doolittle Ph.D., Irina Bancos M.D., Kai Yu M.D., Tamara Tchkonia Ph.D., Nathan LeBrasseur Ph.D., James Kirkland M.D., Ph.D., and David Monroe Ph.D. Drs. LeBrasseur, Tchkonia and Kirkland have financial interests related to this research through Mayo Clinic patents and pending patents covering senolytic drugs and their uses. Other authors report no competing interests.
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