Neuroscientists Kill ‘Zombie’ Cells to Reverse COVID Brain Aging

COVID-19 infection accelerates premature aging in the brain, scientists have found. But there is some good news: we may be able to turn it back.

Using lab-grown mini brains grown from human stem cells, a team of researchers from the University of Queensland in Australia investigated how different variants of SARS-CoV-2 can influence brain tissues.

Each of our cells acts as a tiny molecular factory which carries out the essential processes our bodies need to survive. The problem is, these processes produce dangerous waste products that can build up in our cells over time and cause damage to our DNA and molecular machinery. At a certain point, these cells are essentially shut down and become incapable of cell division. But that does not mean that they are inactive.

These so-called senescent cells, also known as zombie cells, start to produce proteins and other molecules which can lead to inflammation. “Senescent cells are known to drive tissue inflammation and degeneration, leaving patients exposed to cognitive impairments like brain fog and memory loss,” Julio Aguado, a research fellow at the university’s Australian Institute for Bioengineering and Nanotechnology and lead author on this research, said in a statement.

When we are young our immune systems are pretty good at mopping these zombie cells up. But as we age and more cells get shut down, they eventually start to accumulate.

In their study, Aguado and his team found that SARS-CoV-2 actually accelerates this buildup of zombie cells, and thus premature aging.

“We found COVID-19 accelerates the presence of ‘zombie’ or senescent cells, which accumulate naturally and gradually in the brain as we get older,” Aguado said.

But what if there was some way to turn back the biological clock?

“We used the brain organoids [aka the mini brains] to screen a range of therapeutics, looking for any capable of removing those senescent cells,” Aguado said.

In their study, published in the journal Nature Aging, the team found four common drugs selectively destroyed these COVID-induced zombie cells: navitoclax, ABT-737, fisetin and a combination of dasatinib and quercetin.

“More research is needed to fully understand the mechanisms at play, but this study marks a significant step forward in our knowledge of the intricate relationship between viral infections, aging and neurological well-being,” Aguado said. “Long term, we can expect widespread use of these drugs to treat persistent post-acute infection syndromes caused by viral infections like COVID-19.”

As well as showing promise for patients with COVID-induced premature aging, the study acts as a proof of concept for the use of synthetically grown humanlike organs in a laboratory setting. “Our study beautifully demonstrates how human brain models can accelerate the preclinical screening of therapeutics, while also moving towards animal-free testing, with potentially global impacts,” Ernst Wolvetang, an organoid expert at the Australian Institute for Bioengineering and Nanotechnology, said in a statement.

“This same method of drug screening could also help Alzheimer’s research and a whole host of neurodegenerative diseases where senescence is a driver.”