A new class of drugs identified and validated by Mayo Clinic researchers along with collaborators at Scripps Research Institute and others, clearly reduces health problems in mice by limiting the effect of senescent cells -- cells that contribute to frailty and diseases associated with age. The researchers say this is a first step toward developing similar treatments for aging patients. Their findings appear today in the journal Aging Cell.
"If translatable to humans -- which makes sense as we were using human cells in many of the tests - this type of therapy could keep the effects of aging at bay and significantly extend the healthspan of patients," says James Kirkland, M.D., Ph.D., head of the Mayo Clinic Kogod Center on Aging and senior author of the study.
The drugs -- called senolytics -- selectively kill senescent cells without harming nearby cells and tissue, to reduce heart and vascular problems, muscle weakness, osteoporosis, and neurological problems. Senescent cells are cells that appear with aging and at sites of many age-related diseases. They produce factors that can damage the cells and tissues around them and at a distance, amplifying their effects. In many examples, the drugs caused significant and visible reduction of multiple conditions after just one dose - and remained therapeutic for up to seven months. The researchers say that this long lasting effect is consistent with a change in cellular or tissue composition.
The two drugs -- dasatanib and quercetin -- were the most successful of the 46 drugs tested in clearing senescent cells and while partially effective individually, when combined were significantly more effective in visibly reversing signs of aging in mice.
"While far too early to predict a clinical relevance, this work demonstrates a novel and exciting way to address multiple morbidities affecting the elderly, at least in a mouse model of accelerated aging," said Dr. Felipe Sierra, director of the National Institute on Aging's Division of Aging Biology. "It will be interesting to see further senolytics developed and tested in normal mice and other animal models."
More studies are planned and there is no time frame on when the drugs might be used on humans. Dr. Kirkland cautions against any speculation on clinical applications. Both drugs are in use in humans for other purposes, however they would still have to go through clinical trials for this new and unique type of aging therapy.
The research was supported by multiple grants from the National Institutes of Health, and by the Glenn, Ted Nash Long Life, and Noaber Foundations.
Others on the research team include co-first authors Yi Zhu, Ph.D. and Tamara Tchkonia, Ph.D., Husheng Ding, Nino Giorgade, Allyson Palmer, Steven O'Hara, Nicholas LaRusso, Jordan Miller, Carolyn Roos, Grace Verzosa, Nathan LeBrasseur, Joshua Farr, Sundeep Khosla, and Michael Stout, of Mayo Clinic; Adam Gower, Marc Lenburg of Boston University; Yuji Ikeno and Gene Borden, University of Texas at San Antonio and Audie Murphy VA Hospital, San Antonio; Jonathan Wren, Oklahoma Medical Research Foundation; and Sara McGowan, Heike Furhmann-Stroissnigg, Aditi Gurkar, Jing Zhao, Debora Colangelo, Akaitz Dorronsoro, Yuan Yuan Ling, Amira Barghouthy, Diana Navarro, Tokio Sano, Paul Robbins and Laura Niedernhofer, of the Scripps Research Institute in Florida.
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