Running Improves Memory Through Muscle Factor, Could Deter Dementia

That running can boost our memory to the same degree or more than brain training is an old observation that still puzzles scientists worldwide. But a new study by National Institute on Aging scientists is providing information about how that happens and emphasizing that to keep memory from fading, people should keep running.

The study, “Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function,” published recently in the journal Cell Metabolism, has already attracted plenty of media coverage, since the findings overwhelmingly show that people who exercise more also reap the most benefits of improved cognition. It is a recipe that could keep dementia at bay.

Scientists have long studied brain changes triggered by endurance exercise such as running, and they have identified growth factors and other brain-specific molecules that contribute to the building of more neural connections with exercise – but questions still remained regarding the effect of exercise on memory in the very first place.

Attempting to clear confusion, senior author Henriette van Praag at the National Institute on Aging went to what she imagined was the source of the potential changes – the muscles.  Because muscles undergo radical changes when exercised, they might produce some substance that travels through the bloodstream to the brain to impact memory function.

“We wanted to cast a wide net. Rather than focus on a known factor, we did a screen for proteins that could be secreted by muscle tissue and transported to the brain,” said van Praag. Other compounds produced in other parts of the body were excluded because a mechanism called the blood-brain barrier keeps them from the brain.

Starting with muscle cells in a laboratory dish, they looked at molecules produced by the cells during and after a run – but because cells in a dish do not run, they were treated with a chemical that simulated the effect.

Soon enough, one molecule stuck out. Cathepsin-B – a factor explored in a scattered collection of studies ranging from cancer to epilepsy – was present in large quantities in both the cell-growth medium and in the blood and muscles of mice that had been running every day for weeks in another part of the lab.

Additional proof that cathepsin-B could be the missing link between exercise and brain changes came when van Praag observed that it made nerve cells produce many of the factors needed for neuron growth – factors also observed in running animal’s brains in numerous earlier studies.

Researchers then decided to observe what would happen to mice without the factor. A simple memory test, requiring a mouse to learn to navigate with the help of spatial clues, revealed that a week of running improved memory in normal mice.

After one week – the time it took normal, non-exercising mice to pass the test – mice lacking cathepsin-B still struggled. Unlike mice who were allowed daily runs, the memory of the mutant mice did not improve at all after running.

“Nobody has shown before cathepsin B’s effect on spatial learning,” said van Praag, who admitted that the findings might be seen as controversial. Though other studies reported that cathepsin-B might be beneficial, even clearing Alzheimer’s amyloid plaque; other research indicates the opposite by suggesting that the factor can kill neurons.

van Praag is not deterred because many proteins can give radically different effects if present in high or low levels, and under different physiological circumstances.

The team is now focusing on the details of how cathepsin-B boosts the production of other desirable brain molecules.

“Overall, the message is that a consistently healthy lifestyle pays off,” said Dr. van Praag. “People often ask us, how long do you have to exercise, how many hours? The study supports that more substantial changes occur with the maintenance of a long-term exercise regimen.”