ILLUSTRATION BY MIKE AUSTIN

Cleanup duty
New therapies designed to clear senescent cells from the body could keep our aging population healthier longer—and improve outcomes for COVID-19 patients.

When COVID-19 began surging around the world in early 2020, scientists at the University of Minnesota’s Institute on the Biology of Aging and Metabolism (iBAM) swung into action.

“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.”

Laura Niedernhofer and Paul Robbins/BRADY WILLETTE

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. “We felt it was our obligation to do everything we could to help rescue our most vulnerable populations from the lethality of COVID-19,” Niedernhofer says.

But what if there were a drug that could help clear senescent cells and slow the onset of aging and many diseases associated with it, such as heart disease, cancer, type 2 diabetes, and Alzheimer’s disease?

That question led Niedernhofer and Robbins, working with colleagues at 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.”

A new enemy

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 to 60 percent survival rate.

Since the group’s results were published this past summer in the journal Science, “the excitement around senolytics as a COVID-19 treatment has been growing,” Camell says. Now three clinical studies are underway in Minnesota to evaluate the success of treating COVID-19 patients with senolytics. The first trial focuses on hospitalized COVID patients at Mayo Clinic; investigators already have treated most of the 70 patients they want to study, so Niedernhofer expects they’ll have answers about the senolytics’ effectiveness against COVID within months.

A second study, which began this winter, is being conducted by physicians in the Medical School’s Department of Family Medicine and Community Health in nursing homes throughout Minnesota. Half of the people enrolled in the trial will receive a placebo, while the other half will get a senolytic.

A third study will target people with “long COVID,” who suffer brain fog, shortness of breath, fatigue, chronic pain, and other symptoms. Says Robbins: “There’s preliminary evidence that senescent cells increase in long-haulers, so senolytics may be effective in reducing symptoms in these patients.”

Super senolytics

In addition, researchers at iBAM are excited about the many possible uses for therapeutic senolytics beyond healthy aging and COVID-19:

  • Improving vaccine response: Early evidence indicates that senolytics can be used to improve response to a vaccine. Researchers foresee a scenario where people 65 and older might take senolytics for two weeks before getting their jabs.
  • Making kidneys viable for transplant: Senolytics could potentially help to rid older organs, which are not currently eligible for transplant, of senescent cells, thereby making them viable.
  • Tackling viral infections: Scientists also believe that senolytics may prove valuable in reducing mortality from a whole range of viral infections, including pneumonia and sepsis.

Philanthropic funding, including a recent $150,000 gift, directly supports iBAM’s development of new senolytic therapies as well as better biomarkers—simple blood and urine tests—that could aid physicians in quickly diagnosing disease.

“We’re living in a time 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.”

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