How does regular exercise protect against mental decline?

Q. Is it true that regular exercise protects not only against overweight, diabetes, and heart disease, but also against mental decline? If so, how does exercise do all this?

A. We've had solid evidence for many decades that regular exercise offers protection against all of these things. But how? That's been the question. It's easy enough to see how burning calories with regular exercise would protect against weight gain. However, it's been harder to understand how exercise might protect against diabetes, cardiovascular problems, and brain disease.

In 2012, the Harvard Health Letter reported on the discovery at Harvard Medical School of a hormone called irisin (pronounced EYE-ris-in). The hormone was discovered in mice, but then was found in humans as well. Irisin is produced during exercise by the muscles and possibly by other organs, including the brain.

Experiments showed that this molecule turns white fat cells (which store fat) into brown fat cells (which burn fat), and also improves insulin resistance. Such changes reduce body weight and protect against both diabetes and heart disease. Could irisin also explain the beneficial effects of exercise on the brain?

A research report from many of the same Harvard team, published online Aug. 20, 2021, by the journal Nature Metabolism, concludes that it may. When a gene essential to the production of irisin was knocked out in mice from birth, blood levels of irisin were very low and brain cells (neurons) were abnormal. In these mice, exercise did not improve brain function, as it did in mice with an intact gene. This indicated that irisin might indeed be responsible for the beneficial effects of exercise on the brain. To pursue this possibility further, the scientists used gene therapy to introduce new copies of the healthy gene into the mice that had a knocked-out gene. This led the mice to produce high levels of irisin when they exercised — and their cognitive performance improved.

Then the scientists applied the gene therapy to boost levels of irisin in mice that had a disease like Alzheimer's disease. The cognitive performance of the mice improved, as did the brain changes characteristic of Alzheimer's disease. The studies identified one way that irisin may be protecting against the Alzheimer's-like disease of the mouse brain: by reducing brain inflammation.

The lessons from studies of mice do not always prove applicable to humans. Yet the fact that humans have the same irisin molecule as mice offers hope that one day the discovery of irisin may prove to benefit human health. More broadly, this study indicates that the many different health benefits of regular exercise may be caused, at least in part, by one or more hormones generated by exercise.

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