Cleanup duty

A graphic showing a person sweeping out an image of a brain.

When COVID-19 began surging around the world in early 2020 and physicians were confronting a deadly disease they knew little about, scientists at the University of Minnesota’s Institute on the Biology of Aging and Metabolism (iBAM) swung into action to help.

“Early in the pandemic it became very clear that certain people were at greatest risk—the elderly, people with diabetes, and people with obesity,” says Laura Niedernhofer, professor of biochemistry in the Medical School and director of iBAM. “And one common thread between those groups? They all have increased levels of senescent cells.”

Senescent cells are aging cells that have stopped dividing but haven’t died. According to Niedernhofer, the burden of senescent cells in our body doubles with every decade of life.

“Senescent cells drive inflammation, and that inflammation then puts you at greater risk for disease and aging,” explains iBAM associate director Paul Robbins, also a professor of biochemistry in the Medical School. “If you have a perfectly healthy, robust immune system, your body clears these cells for you. But as we age, our immune response wanes and stops clearing these cells effectively.”

Niedernhofer, Robbins, and their iBAM colleagues didn’t wait to be asked if their research into senescent cells could be applied to fight COVID-19 infections, too. “This was really an instant reaction,” recalls Niedernhofer. “We’re here to think about the biology of aging, but more importantly, we’re here to help older Minnesotans. We felt it was our obligation to do everything we could to help rescue our most vulnerable populations from the lethality of COVID-19.”

What if there were a drug that could help clear senescent cells and slow the onset of not just the aging process, but of the many diseases associated with aging, such as heart disease, cancer, type 2 diabetes, and Alzheimer’s disease?

That question led Niedernhofer and Robbins, working with colleagues at the Mayo Clinic, to become the first scientists to describe a new class of drugs called senolytics in 2015. More recently, they’ve shown that fisetin, a natural antioxidant found in various fruits and vegetables (apples, strawberries, onions, and cucumbers, for example), successfully clears senescent cells in mice.

“We do have preliminary data [indicating] that fisetin clears senescent cells in humans,” says Niedernhofer, “and there are now many clinical trials underway to study it further.”

When COVID-19 struck, iBAM scientists quickly geared up to see whether the senolytics they were developing to promote healthier aging could also be used to treat the viral infection caused by SARS-CoV-2.

In a study led by iBAM investigator Christina Camell, researchers exposed aged mice to a coronavirus closely related to SARS-CoV-2. In the control group, all of the infected mice died; mice treated with a senolytic, however, had a 50–60% survival rate.

“The excitement around senolytics as a COVID-19 treatment has been growing,” says Camell, since the group’s results were published last summer in the prestigious journal Science. Clinical studies are under way in Minnesota to evaluate the success of treating COVID-19 patients with senolytics. 

Investment to outcomes

In 2015, the Minnesota Legislature’s higher education funding bill included an unprecedented $30 million investment that allowed the U of M’s Medical School to establish four new Medical Discovery Teams (MDTs). The MDTs were designed to propel already strong programs into world-class research cohorts dedicated to addressing some of the state’s most pressing health care priorities: addiction, rural and Native American health, optical imaging and brain science, and the biology of aging.

That investment brought top researchers like Niedernhofer and Robbins to the U to continue building on their leading-edge research.

“The University of Minnesota has been an incredibly rich backdrop for our work studying the biology of aging,” says Niedernhofer, “providing so many opportunities for collaborations with colleagues across campus to find new applications for senolytics in treating diseases in the elderly.”

And with the state’s (and the world’s) aging population growing, there’s no better time for progress.

“We’re living in a time on this planet where the elderly population is doubling,” says Niedernhofer, “and each of those elderly people has an average of two chronic diseases. By targeting the biology of aging itself, instead of targeting specific diseases, with this new class of drugs called senolytics, we may be able to help people live healthier for a longer time.”