Research by Mayo Clinic suggests that senolytic drugs could improve bone health in older women by targeting senescent cells, with the most significant benefits observed in those with higher cell counts, pointing to the importance of tailored treatments.
Mayo Clinic researchers have found that drugs targeting senescent, or “zombie,” cells could benefit healthy older women, but they are not universally effective. According to a recent study published in Nature Medicine, these drugs may only be helpful for individuals with a high concentration of senescent cells.
Senescent cells are damaged cells that lapse into a state of dormancy. These cells, often called “zombie cells,” can’t divide but can contribute to inflammation and tissue damage associated with aging and chronic disease. Senolytic drugs are designed to eliminate these cells, potentially reducing age-related health issues.
Research Findings From Mayo Clinic
In a 20-week, phase 2 randomized controlled trial, 60 postmenopausal women intermittently took a combination of FDA-approved dasatinib and quercetin, a natural compound found in certain foods. This trial marks the first investigation of intermittent senolytic therapy in healthy aging women, using bone metabolism changes as a measure of effectiveness.
Researchers found that this combination, known as D+Q, had beneficial effects on bone formation but did not reduce bone resorption or the breakdown and removal of bone tissue. Furthermore, D+Q mainly benefited people with evidence of a high number of senescent cells. This group had more robust increases in bone formation, decreases in bone resorption, and an increase in bone mineral density at the wrist.
The Future of Anti-Aging Treatments
“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 says more research is needed to better identify people who may benefit from senolytic treatments and to develop more specific and potent senolytic drugs that may show efficacy in more people. People who have experienced “accelerated aging” — such as cancer survivors after chemotherapy, or those with progeroid syndromes – may have increased numbers of senescent cells.
Broader Implications for Disease Treatment
Besides their application to aging, senolytic drugs may be useful against certain diseases, such as idiopathic pulmonary fibrosis, dementia, diabetes, heart disease, and others, Dr. Khosla says. However, these drugs will likely need to be customized according to their potency and the amounts of senescent cells in the diseased tissues.
Reference: “Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial” by Joshua N. Farr, Elizabeth J. Atkinson, Sara J. Achenbach, Tammie L. Volkman, Amanda J. Tweed, Stephanie J. Vos, Ming Ruan, Jad Sfeir, Matthew T. Drake, Dominik Saul, Madison L. Doolittle, Irina Bancos, Kai Yu, Tamara Tchkonia, Nathan K. LeBrasseur, James L. Kirkland, David G. Monroe and Sundeep Khosla, 2 July 2024, Nature Medicine.
DOI: 10.1038/s41591-024-03096-2
The study was supported by National Institutes of Health grant nos. R21 AG065868, P01 AG062413, R01 AG 076515, R01 DK128552, R01 AG055529, R37 AG13925 and R33 AG61456.
Co-authors are 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, including Mayo Clinic patents and pending patents covering senolytic drugs and their uses. The remaining authors declare no competing interests.