Targeting Senescent Cells Increases Bone Mass

Mayo Clinic researchers in Rochester, Minnesota, have found that targeting senescent cells—aging cells—led to an increase in bone mass and strength. The findings, titled “Targeting cellular senescence prevents age-related bone loss in mice” appear online in the August 21, 2017 edition of Nature Medicine.

“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,” says Sundeep Khosla, M.D., director of the Aging Bone and Muscle program at Mayo Clinic’s Robert and Arlene Kogod Center on Aging and a co-author on the study, in the August 21, 2017 news release.

“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.”

According the Mayo Clinic’s news release, “In the study, researchers used multiple approaches to target senescent cells in mice with established bone loss between 20 and 22 months of age. That’s the equivalent of over age 70 in humans. Approaches included using: a genetic model where senescent cells can be killed off; a pharmacological approach, where senolytic drugs previously developed at Mayo Clinic eliminate senescent cells; a Janus kinase inhibitor—a drug that blocks the activity of Janus kinase enzymes—to eliminate the toxic products produced by senescent cells.”

“The benefits on bone found in elderly mice were not evident in younger mice. That, coupled with the finding that the senolytic drugs were effective when given only intermittently, supports the link between senescent cells and age-related bone loss. Researchers administered a senolytic drug combination (dasatinib and quercetin) once per month 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,” says James Kirkland, M.D., Ph.D., director of the Kogod Center on Aging and co-corresponding author of the study. “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.”

Dr. Khosla commented to OTW, “To our knowledge, this is the first study showing that treating a fundamental aging mechanism that is present in all tissues—cellular senescence—can prevent bone loss with aging. This opens up the possibility of using compounds that target this mechanism in all tissues, thereby ameliorating or preventing multiple age-associated co-morbidities, including osteoporosis, frailty, vascular disease, and metabolic dysfunction. Our next steps are to continue to explore additional ‘senotherapeutic’ compounds in animal models and move the most promising of these to early phase human studies.”