Senescent cells (damaged or non-functioning cells that persist in the body) contribute to many aspects of aging and illness, including inflammation and multiple chronic diseases. Based on the "Amplifier/Rheostat Hypothesis" of senescent cells developed at Mayo, the researchers sought to discover 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, provoking 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 related to SARS-CoV-2 using a model developed at University of Minnesota, showed an amplified reaction, with increased senescent cells, inflammation, and nearly 100 % mortality. When the researchers treated similar mice - before or after the infection - with senolytics, drugs that selectively remove senescent cells from the body, the result was the opposite. Anti-viral antibodies increased, while signs of inflammation and senescent cells significantly decreased along with mortality, so survival of the old, infected mice became more like that of younger mice.
The researchers suggest that reducing the existing burden of senescent cells in older or chronically-diseased patients may increase their resilience and decrease their risk of dying from viral infections, including SARS-CoV-2. Three such clinical trials are now underway.
"Even though vaccine use is growing, senolytics could still be helpful to those who cannot receive the vaccine, and especially to older individuals in nursing homes with comorbidities or immunity issues," says James Kirkland, M.D., Ph.D., director of the Kogod Center on Aging and, together with Tamar Tchkonia, Ph.D., senior author for Mayo Clinic on the study. The study suggests senolytics could also improve response of the elderly 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 University of Minnesota Clinical and Translational Science Institute; the Medical Discovery Team on the Biology of Aging; and The Irene Diamond Fund/American Federation on Aging Research Postdoctoral Transition 10 Award. Also, by the Fesler-Lampert Chair in Aging Studies and the AFAR Junior Faculty Award.