An article appearing August 21, 2017 in Nature Medicine reveals a potential role for senolytic compounds, including quercetin and the drug dasatinib, in the targeting of senescent cells to help maintain bone. “While we know from previous work that the accumulation of senescent cells causes tissue dysfunction, the role of cell senescence in osteoporosis up to this point has been unclear,” noted researcher Sundeep Khosla, MD, of the Mayo Clinic’s Robert and Arlene Kogod Center on Aging. “The novelty of this work for the bone field lies in the fact that, rather than targeting a bone-specific pathway, as is the case for all current treatments for osteoporosis, we targeted a fundamental aging process that has the potential to improve not only bone mass, but also alleviate other age-related conditions as a group.”
The team targeted senescent cells in aged mice with bone loss by several methods, including quercetin plus dasatinib, a genetic model, and a drug that blocks the activity of Janus kinase enzymes to eliminate senescent cell byproducts. “The effects of all three approaches on aging bone were strikingly similar,” Dr Khosla reported. “They all enhanced bone mass and strength by reducing bone resorption but maintaining or increasing bone formation, which is fundamentally different from all current osteoporosis drugs.”
Dr Khosla’s team determined that the senolytic drugs were only effective when intermittently administered. Dasatinib and quercetin were only given monthly to eliminate senescent cells. “Even though this senolytic drug combination was only present in the mice for a couple of hours, it eliminated senescent cells and had a long-lasting effect,” noted co-corresponding author James Kirkland, MD, PhD. “This is another piece of the mounting evidence that senolytic drugs are targeting basic aging processes and could have widespread application in treating multiple chronic diseases.”
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