On Jun. 8, 2021, Mayo Clinic researchers and colleagues at the University of Minnesota showed that COVID-19 exacerbates the damaging impact of senescent cells in the body. In preclinical studies, the senolytic drugs discovered at Mayo significantly reduced inflammation, illness, and mortality from COVID infection in older mice. The findings appear in the journal Science.

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.

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