Senolytics reduce symptoms of COVID-19 in preclinical studies
ROCHESTER, Minn. – Researchers and colleagues at the Mayo Clinic at the University of Minnesota have shown that COVID-19 exacerbates the damaging impact of senescent cells in the body. In preclinical studies, senolytic drugs discovered in Mayo significantly reduced inflammation, disease, and mortality from COVID infection in older mice. Results appear in the journal Science.
Senescent cells (damaged or non-functioning cells that persist in the body) contribute to many aspects of aging and disease, including inflammation and multiple chronic diseases. Based on the senescent cell “amplifier / rheostat hypothesis” developed in Mayo, researchers set out to find out how COVID-19 causes much higher mortality in the elderly and chronically ill. They showed that human senescent cells have an amplified response to the SARS spike protein, causing increased production of factors causing inflammation and tissue damage by senescent cells.
The researchers also found that older mice infected with viruses, including a coronavirus linked to SARS-CoV-2 using a model developed at the University of Minnesota, exhibited an amplified response, with an increase senescent cells, inflammation and nearly 100% mortality. When researchers treated similar mice – before or after infection – with senolytics, drugs that selectively remove senescent cells from the body, the result was the opposite. Antiviral antibodies increased, while signs of inflammation and senescent cells decreased dramatically with mortality, so that the survival of older infected mice became more similar to that of younger mice.
Researchers suggest that reducing the existing burden on senescent cells in older or chronically ill patients may increase their resilience and reduce their risk of dying from viral infections, including SARS-CoV-2. Three of these clinical trials are currently underway.
“Even as vaccine use increases, senolytics could still be helpful for those who cannot receive the vaccine, and especially for older people in nursing homes with co-morbidities or immunity issues,” said said James Kirkland, MD, Ph.D., director of the Kogod Center on Aging and, with Tamar Tchkonia, Ph.D., lead author of the study for the Mayo Clinic. The study suggests that senolytics may also improve the response of older people to vaccines and help them fight bacterial and other viral infections.
The research was supported by the National Institutes of Health; the Connor Fund; Robert J. and Theresa W. Ryan; Robert P. and Arlene R. Kogod; the Noaber Foundation; the Institute of Clinical and Translational Sciences, University of Minnesota; the Biology of Aging Medical Discovery Team; and Irene Diamond Fund / American Federation on Aging Research Postdoctoral Transition 10 Award. Also by the Fesler-Lampert Chair in Studies on Aging and the AFAR Junior Faculty Prize.
About the Mayo Clinic
Mayo Clinic is a non-profit organization committed to innovation in clinical practice, education, and research, and providing compassion, expertise, and answers to all in need of healing. Visit the Mayo Clinic News Network for more information on the Mayo Clinic. For more information on COVID-19, including the Mayo Clinic Coronavirus Map Tracker, which has 14-day forecasts of COVID-19 trends, visit the COVID-19 Resource Center at the Mayo Clinic.
Bob Nellis, Mayo Clinic Public Affairs, [email protected]
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