Scientists Discover Enzyme That Could Result In A Drug Substitute For Exercise

MARY LOUISE KELLY, HOST:

Scientists say they have identified an enzyme that could help explain how exercise can slow or even reverse some signs of aging in the brain. Exercise in a bottle is not around the corner, but it's not out of the question either. NPR's science correspondent Richard Harris took a break from reporting about the coronavirus to look into this intriguing suggestion.

RICHARD HARRIS, BYLINE: Scientists were surprised to discover a few years ago that brain function doesn't have to get worse and worse as we age. Saul Villeda's research was inspired in part by a finding that parts of the brain can actually regrow, even in older people.

SAUL VILLEDA: Just because you have an old brain, it doesn't have to stay that way. And one of the best-known interventions that has a benefit on the brain is exercise. The problem is that the elderly are frail. Many of them can't physically do the exercise.

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HARRIS: Villeda and his colleagues at UC San Francisco have been on the hunt for factors in the blood that are boosted by exercise and that can improve mental performance.

VILLEDA: Can we actually then transfer the benefits of exercise without actually having to do the physical component of the exercise itself?

HARRIS: They now report in Science magazine that they think they have a great lead. Mice who exercise produce lots of a liver enzyme called GPLD1. And when the researchers revved up production of this protein in mice, nerves grew in part of their brains, and the animals perform better on mental tasks in a maze.

VILLEDA: Exercise causes this protein to be produced in the liver, goes into the blood. That sort of dampens certain aspects of inflammation. And then the result of that is that you actually have improvement in cognitive function in these older mice.

HARRIS: The research team also looked at a group of older people who exercise more, and, there again, they found more of this enzyme.

VILLEDA: So the same thing is true in humans. If you're more active, you're producing more of this protein, and it's sort of circulating in your blood.

HARRIS: Now, both aging and exercise are extremely complicated systems involving all sorts of components that interact in complicated ways. So Villeda had to think hard about whether a single protein could really have a big effect.

VILLEDA: I was surprised that one protein could have that much effect. But when I started thinking about it, OK, it's one protein but really, it's changing, you know, these other hundred proteins. So I think that's why.

HARRIS: Scientists are nowhere near understanding the complex relationship between all these interacting parts. Bradley Wise is at the National Institute on Aging.

BRADLEY WISE: There's a long step between identifying this enzyme and making, say, a pill out of that. This is one piece of the puzzle.

HARRIS: But the team at UC San Francisco is eager to see if they can find their way to making a medication out of their now-patented discovery. Villeda says the discovery at least suggests a path forward.

VILLEDA: We don't have that, you know, exercise pill right now. You know, this lets us know that that, I think, is a viable thing to pursue, but we're not there yet. You know, my mom gets really excited. She goes like, oh, exercise in a bottle. I'm like, we're on our way, but we're not there yet.

BILL FREEMAN: I wouldn't rush out to make GPLD1 and give it to people.

HARRIS: Bill Freeman researches aging at the Oklahoma Medical Research Foundation and at the VA in Oklahoma City. He's excited about the new findings but cautions that almost nothing is known about the potential downside of tinkering with this enzyme and the complicated system it affects.

FREEMAN: There's a lot more research to be done, and in the meantime, one of the things that we can all do is exercise. We can - we have that within our own power.

HARRIS: And exercise has all sorts of health benefits beyond the brain. So if this ever does become a medication, it would be most helpful for people who, through injury or old age, simply can't exercise on their own. Richard Harris, NPR News. Transcript provided by NPR, Copyright NPR.