Experiments showed that blood levels of cathepsin B rose in mice that spent a lot of time on their exercise wheels. What's more, as levels of the protein rose, the mice did better on a memory test in which they had to swim to a platform hidden just beneath the surface of a small pool.
The team also found evidence that, in mice, cathepsin B was causing the growth of new cells and connections in the hippocampus, an area of the brain that is central to memory.
But the researchers needed to know whether the substance worked the same way in other species. So they tested monkeys, and found that exercise did, indeed, raise circulating levels of cathepsin in the blood.
Next, they studied 43 people who hadn't been getting much exercise.
"The people were university students that were couch potatoes — they didn't exercise much," says Dr. Emrah Duzel, a neurologist and team member from the German Center for Neurodegenerative Diseases.
Half the students remained sedentary. The other half began a regimen of tough treadmill workouts several times a week.
"Within four months we really made them fit," Duzel says.
And, just like mice, the students who exercised saw their cathepsin B levels rise as their fitness improved. They also got better at a memory task: reproducing a geometric pattern they'd seen several minutes earlier.
But the clincher was the link between memory improvement and cathepsin levels, Duzel says.
"Those individuals that showed the largest gains in memory also were those that had the largest increase in cathepsin," he says.
Of course, cathepsin is probably just one of several factors linking exercise and brain function, van Praag says.
"I don't think we have fully explained how exercise improves memory," she says, "but I think we've made a significant step forward."
Also, cathepsin has a dark side. It's produced by tumor cells and has been linked to the brain plaques associated with Alzheimer's. So, trying to artificially raise levels might not be a good idea, van Praag says.
However van Praag says she's trying to keep her own cathepsin levels up naturally by jogging — when she can.