Why exercise gets harder the less you do it

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Doing less exercise could deactivate a vital protein in the body, causing further inactivity and making exercise more difficult, new research suggests.

Scientists at the University of Leeds have discovered that deactivating the Piezo1 protein, a blood flow sensor, reduces the density of capillaries carrying blood to the muscles.

This restricted blood flow means activity becomes more difficult and can lead to a reduction in how much exercise is possible, the team found.

The results, published in the Journal of Clinical Investigation, may help to explain the biology of why exercise becomes harder the less you do it.

Exercise is known to protect against cardiovascular disease, diabetes, depression, and cancer.

“Unfortunately, many people fail to exercise enough, for reasons such as injury and computer usage. This puts people at more risk of disease. The less people exercise, the less fit they become, often leading to a downward spiral,” said lead author Fiona Bartoli, a Postdoctoral Researcher in the University’s School of Medicine.

Although many responses to exercise are known, how the benefits of exercise are initially triggered at a molecular level has remained mysterious.

“Our study highlights the crucial link between physical activity and physical performance made at this level by Piezo1. Keeping our Piezo1s active by exercising may be crucial in our physical performance and health,” Bartoli said.

While the experiments were carried out in mice, the Piezo1 protein is found in humans, suggesting the same results could occur.

During the experiment, scientists compared two groups of mice – a control group, and a group whose Piezo1 levels had been disrupted for 10 weeks.

Walking, climbing, and running wheel activity was observed, with the Piezo1 mice showing a striking reduction in activity levels. This suggests an important role for Piezo1 in sustaining normal physical activity.

The researchers considered whether the Piezo1 mice were less interested in exercise, but they found no differences in the amount or duration of activity between the two groups.

Instead, there were fewer running wheel revolutions per exercise session, and slower running speed, suggesting a lowered ability to exercise, without a lesser desire.

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