Senescent cell research moves into human trials

Rochester, Minn. — Mayo Clinic researchers, along with collaborators from Wake Forest School of Medicine and the The University of Texas Health Sciences Center at San Antonio, have published findings from a safety and feasibility clinical trial on the removal of senescent cells from a small group of patients with pulmonary fibrosis. The findings appear in EBioMedicine.

While lung function, clinical test outcomes, frailty levels and overall health among the patients did not change, all 14 participants showed clinically meaningful improvement in physical function in nine doses over three weeks. That ability was measured in four tests: gait speed, walking speed in six minutes, a chair rise test and a score related to a bank of physical function tests.

“This was a short safety trial to determine if we should move ahead with actual large-scale human trials,” says senior author James Kirkland, M.D., Ph.D., head of the Robert and Arlene Kogod Center on Aging. “It’s important to emphasize that, while some measurable improvement was noted in all the participants, this is simply the start of human studies. We don’t know what lies ahead.” Senescent or semidormant cells (sometimes called “zombie cells”) form in many areas of the body and cause aspects of aging and frailty, ranging from osteoporosis to diabetes and muscle weakness. In this case, researchers are focusing on idiopathic pulmonary fibrosis, a progressive and fatal condition that is related to senescent cells. The researchers used a drug called a senolytic – dasatinib plus quercetin, an open-label drug, to clear the senescent cells.

“We are studying the effectiveness of this and other senolytic drugs, but that does not mean that these should be used by patients or prescribed by physicians for any off-label conditions,” says Dr. Kirkland. “I want to emphasize that no one should take these drugs. This research is only beginning.”

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Co-first authors of the article are Jamie Justice, Ph.D., Wake Forest School of Medicine, and Anoop Nambiar, M.D., UT Health. Other collaborating institutions were the South Texas Veterans Health Care System and the University of Central Florida. The research was funded by the National Institutes of Health; the Claude Pepper Older Americans Independence Centers; The Connor Group; Robert and Theresa Ryan; John and Virginia Kunkel; and the Noaber, Ted Nash Long Life and Glenn Foundations. The research was not supported by any private industry or other for-profit agencies. The Mayo researchers have a financial interest in this research. Patents on senolytic drugs are held by Mayo Clinic.

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