Stamford Advocate

Team developing COVID drug to reverse aging

- By Jordan Fenster

The older you are, the more likely your COVID-19 infection will be more severe, and even fatal. Of the nearly 5,000 COVIDrelat­ed deaths in Connecticu­t to date, 81 percent are people over 70 years old.

But what if you could turn back the clock? A team of researcher­s at the University of Connecticu­t are working on ways to literally reverse the effects of aging as a way to mitigate the severity of a COVID infection.

“The goal here is not to erase aging, but rather we’re testing interventi­ons that are designed to slow the rate of biological aging and therefore help prevent severe COVID,” according to George Kuchel, director of UConn’s Center on Aging and chief of geriatric medicine at UConn Health.

One drug in particular, called compound RTB101, can theoretica­lly not only slow aging but boost the immune response, helping the body and any potential vaccines do their jobs better.

That’s important because, as Kuchel said, “these vaccines don’t work as well on older adults.”

“Even if the vaccine turns out to be as effective as the initial studies suggest, there’s a very strong likelihood that it’s going to be less effective in older adults,” he said. “These kinds of approaches are going to be important as additional therapies to the vaccine, for the vaccine alone is not going to be sufficient.”

Another weakness of any potential vaccine is its specificit­y. The COVID-19 pandemic may be contained, but the virus could mutate, or another virus might emerge.

“At some point, we’re going to be done with COVID-19, hopefully,” Kuchel said. “But I think we all agree that there could very well be another COVID, whether it’s COVID-21, -22, whatever, or another pathogen out there that we don’t even know about yet.

“And if older adults are more vulnerable to get this and to die from it, then we believe this approach will be helpful irrespecti­ve of what the infection is.”

How it works

The compound known as RTB101 doesn’t actually make you younger. There’s a difference,

Kuchel said, between chronologi­cal age — how many years you have been alive — and biological age.

“Whereas biological aging is an effort to capture the rate of aging, how fast somebody ages,” Kuchel said. “As you can imagine, you could have two people who are both 70 years old, and one could have a biological age which would be younger than most 70-yearolds, and another one who has a biological age that would be older than most 70-year-olds.”

RTB101 targets the biological pathways that control the aging process, the so-called “mTOR pathway,” for example.

Early versions of the compound have been studied for decades — at Connecticu­t’s Jackson Labs and elsewhere — and have been shown to slow aging in mice.

While inhibiting the natural processes that lead to biological aging, the compound also boosts the body’s ability to fight disease.

“There are a lot of genes that are involved in our ability to fend off viral infections,” Kuchel said. “There are these inflammato­ry molecules called ‘interferon gamma.’ That whole family of molecules is very important to our ability to fend off infection, particular­ly viral infections. What this compound does is it boosts those responses. So it down-regulates mTOR and it up regulates the interferon gamma responses.”

“In a sense, it kind of resets the body to behave the way it would have at a younger age, and to boost immune responses,” Kuchel said.


The work on RTB101 is being funded by the National Institutes for Health and the first step — which the team at UConn is currently recruiting subjects for — is a small-scale feasibilit­y study involving people over the age of 65 who have either been recently diagnosed with a COVID-19 infection or who lives with someone diagnosed with COVID in the last few days.

“We’re in a very tight timeline,” Kuchel said. “We need to do this in the next two months.”

But don’t expect your doctor to prescribe an anti-aging drug any time soon.

After the feasibilit­y study will come a large-scale, multi-site clinical trial. Only then will Kuchel and his team seek FDA approval.

“I know that sometimes the progress of science seems maddeningl­y slow. But unfortunat­ely, it’s the only way we can show that it works,” Kuchel said. “In terms of this being available at physician’s offices, it’s not going to be within the next year or two. This is going to take some time.”

But, again, this sort of research could be important, Kuchel said, because it is not a therapy to treat or prevent any specific disease.

“We believe that will be transforma­tive not only for the current COVID pandemic, but for future pandemics, future infections, which we know are going to happen,” he said.

“We know that future infections will happen, we know that older adults will be more vulnerable. That’s absolutely clear. The only thing we don’t know is what the pathogen will be.

“With this approach, the argument can be made that we don’t need to know what that pathogen is because we’re not targeting the pathogen, we’re targeting the person.”

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