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July 2, 2024 – Researchers at the Mayo Clinic have discovered that senolytic drugs, which target and eliminate senescent “zombie” cells, may offer health benefits to some older women, but these benefits are not universal. The study, published in Nature Medicine, emphasizes the need for personalized approaches in using these drugs.
Senescent cells are malfunctioning cells that enter a dormant state, ceasing to divide yet contributing to chronic inflammation and tissue dysfunction associated with aging and various chronic diseases. Senolytic drugs are designed to clear these harmful cells from the body, potentially mitigating their negative effects.
In a 20-week, phase 2 randomized controlled trial, 60 postmenopausal women were intermittently administered a combination of FDA-approved dasatinib and quercetin, a natural compound found in several foods. This study marks the first randomized controlled trial to explore intermittent senolytic treatment in healthy aging women, using bone metabolism as an efficacy marker.
Key Findings
The study found that the dasatinib and quercetin (D+Q) combination positively influenced bone formation but did not reduce bone resorption, the process of breaking down bone tissue. Importantly, the beneficial effects were more pronounced in participants with a high number of senescent cells, as indicated by increases in bone formation, decreases in bone resorption, and improved bone mineral density at the wrist.
Dr. Sundeep Khosla, the senior author and an endocrinologist at the Mayo Clinic, cautioned against the widespread use of commercial products like quercetin for anti-aging purposes without understanding individual senescent cell levels or optimal dosing regimens. “Many people are using these products without knowing if they have enough senescent cells to benefit or what dose is needed to be effective yet safe,” Dr. Khosla said.
Future Directions
The research highlights the necessity for further studies to better identify individuals who might benefit from senolytic treatments and to develop more targeted and potent senolytic drugs. This could be particularly relevant for individuals who have experienced “accelerated aging,” such as cancer survivors post-chemotherapy or those with progeroid syndromes, who may have higher levels of senescent cells.
In addition to their potential role in combating aging, senolytic drugs might also be effective against diseases such as idiopathic pulmonary fibrosis, dementia, diabetes, and heart disease. However, the efficacy of these drugs will likely depend on their potency and the number of senescent cells present in the affected tissues.
Research Support and Conflicts of Interest
The study was funded by several grants from the National Institutes of Health, including 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.
It is worth noting that Drs. LeBrasseur, Tchkonia, and Kirkland have financial interests related to this research, including Mayo Clinic patents and pending patents on senolytic drugs and their uses. The other authors declared no competing interests.
As this research progresses, it holds promise for more effective and personalized treatments targeting age-related conditions and chronic diseases, potentially enhancing the health and quality of life for older adults.
