Senolytic Therapies May Reduce COVID-19 Mortality in the Elderly
The therapy was associated with reduced mortality, cellular senescence and inflammatory markers.
A recent preclinical study conducted by investigators from the University of Minnesota Medical School, in collaboration with the Mayo Clinic, has discovered that senolytic therapies significantly reduced mortality in older mice infected with a beta-coronavirus that is closely related to SARS-CoV-2.
Results from the study were published in the journal Science.
"We wanted to determine if therapeutically targeting fundamental aging mechanisms, such as cellular senescence, could reduce morbidity and mortality following viral infection," Christina Camell, an assistant professor in the department of Biochemistry, Molecular Biology and Biophysics and a first author of the study said.
The team of investigators wanted to understand why the elderly were so much more vulnerable to the adverse outcomes associated with COVID-19. One hypothesis was senescent cells, so they removed them in older mice using senolytic therapies.
The team exposed both older and younger mice to a mouse beta-coronavirus and found that the older mice had a near 100% mortality rate, while the younger mice barely got sick.
When the older mice were treated with a senolytic following their infection, the rate of survival increased to 50%. The senolytic therapies were seen to reduce mortality, cellular senescence, inflammatory markers and increased anti-viral antibodies.
"We have been working on a new approach to help the elderly remain healthy, which is to find therapeutics to treat aging rather than treating each individual disease associated with old age. The fact that senolytics worked to protect old organisms from a viral infection proves that approach is accurate," Paul Robbins, a co-director of the Institute on the Biology of Aging and Metabolism at the U of M Medical School said. "By getting rid of a piece of aging biology, senescent cells, with senolytics, the older mice were able to withstand the stress of infection. This suggests that reducing the burden of senescent cells in ill or elderly individuals could improve their resilience and reduce their risk of dying from COVID-19."
The research has led to the initiation of 2 clinical trials looking at how to reduce mortality in eldery patients with a COVID-19 infection. The team also has plans for future research looking to see if senescent cells contribute to the long-hauler effect in many COVID-19 survivors.