How exercise could help keep your memory sharp and lower the risk of dementia

A fascinating new study shows how exercise can boost brain health. The study was done on mice, but it found that a hormone produced by muscles during exercise can enter the brain and improve the health and function of neurons, increasing thinking and memory in both healthy animals and those with a rodent version of Alzheimer’s disease will improve. Previous research shows that people produce the same hormone while exercising, and taken together, the results suggest that exercise could alter the course of memory loss with aging and dementia.

We already have a lot of evidence that exercise is good for the brain. Studies in humans and animals show that exercise stimulates the formation of new neurons in the brain’s memory center, and then helps these new cells survive, mature, and integrate into the brain’s neural network where they can aid in thinking and remembering. Large-scale epidemiological studies also show that active people tend to develop Alzheimer’s disease and other forms of dementia much less than people who rarely exercise.

Irisin helps in the formation of brown fat and stimulates our metabolism

But how does training affect the inner workings of our brain on a molecular level? Scientists have speculated that exercise could directly alter the biochemical environment in the brain without involving the muscles. Alternatively, during physical activity, the muscles and other tissues can release substances that travel to the brain and stimulate processes there, which leads to a subsequent improvement in brain health. Then the substances would have to be able to pass the protective and usually impermeable blood-brain barrier that separates our brain from the rest of our body.

These confused topics were of particular interest to a large group of scientists at Harvard Medical School and other institutions a decade ago. In 2012, some of these researchers, led by Bruce Spiegelman, the Stanley J Korsmeyer Professor of Cell Biology and Medicine at the Dana-Farber Cancer Institute and Harvard Medical School, identified a previously unknown hormone that was found in the muscles of laboratory rodents and humans during movement and is then released into the bloodstream. They named the new hormone Irisin after the messenger god Iris in Greek mythology.

They followed the flight of irisin in the blood and often found it in adipose tissue, where it was soaked up by fat cells and triggered a cascade of biochemical reactions that helped turn normal white fat into brown. Brown fat is more metabolically active than the much more common white fat. It burns a lot of calories. So by helping with the formation of brown fat, Irisin helps boost our metabolism.

Young mice, older animals, and even those with advanced cases of rodent Alzheimer’s disease performed better on tests of their memory and learning ability

But dr. Spiegelman and his colleagues suggested that irisin could also play a role in brain health. A 2019 study by other researchers showed that irisin is produced in the brain of mice after exercise. This previous research had also found the hormone in most human brains that were donated to a large brain bank – unless the donors died of Alzheimer’s disease, in which case their brains contained virtually no irisine.

This study strongly suggests that irisin reduces the risk of dementia. And in the new study just published in Nature Metabolism, Spiegelman and his coworkers wanted to quantify how.

They started by raising mice that were unable to produce irisin from birth, and then let these and other normal, adult mice walk on wheels for a few days, which the animals seem to like to do. This type of training usually increases the subsequent performance in memory and learning tests in rodents that occurred in normal runners. But the animals that were unable to make irisin showed few cognitive improvements, leading the researchers to conclude that irisin is essential for movement to improve thinking.

Then they took a closer look at the brains of running mice with and without the ability to make irisin. All contained more newborn neurons than the brains of sedentary mice. But in the animals without irisin, these new brain cells appeared strange. They had fewer synapses, the connections where brain cells send and receive signals, and dendrites, the snake tendrils that allow neurons to connect to the neural communication system. These newly formed neurons would not easily integrate into the existing network of the brain, the researchers conclude.

But when scientists used chemicals to raise levels of irisin in the blood of animals that were unable to make them themselves, the situation in their brains changed noticeably. Young mice, older animals, and even those with advanced cases of rodent Alzheimer’s disease performed better on tests of their memory and learning ability. The researchers also found signs of decreased inflammation in the brains of animals with dementia, which is important since neuroinflammation is believed to accelerate the progression of memory loss.

Importantly, they also confirmed that irisin flows to and crosses the blood-brain barrier. After the researchers injected the hormone into the genetically engineered mice’s bloodstream, it appeared in their brains, even though their brains couldn’t have produced it.

Overall, these new experiments strongly suggest that irisin is a key element in “linking movement with cognition,” Spiegelman said.

It could also one day be developed as a drug. He said he and his staff, including Christiane Wrann, assistant professor at Massachusetts General Hospital and Harvard Medical School and lead author of the new study, hope to finally test whether pharmaceutical versions of irisin slow cognitive decline, or even that Thinking skills could improve in people with Alzheimer’s.

However, this was a mouse study, and much research remains to be done to see if our brains react to irisin like rodents. It is also not known how much or what types of movement could best enhance our iris levels. But even now, says Wrann, the study reinforces the idea that exercise can be “one of the most important regulators” of brain health. – New York Times

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