Why Exercise Gets Harder the Less You Do

New research out of the University of Leeds offers a molecular explanation for why exercise is harder after sedentary periods. Their findings suggest that inactivity deactivates Piezo1 protein, a blood flow sensor that reduces the density of capillaries carrying blood to muscles. In turn, this restricted blood flow means activity becomes more difficult and can lead to a reduction in how much exercise is possible.

“Exercise protects against cardiovascular disease, diabetes, depression and cancer,” says lead author Fiona Bartoli, a postdoctoral researcher in the University of Leeds’ School of Medicine. “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.”

The team 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. The researchers also considered whether the Piezo1 mice were just less interested in exercise. However, they found no differences in the amount or duration of activity between the two groups—the difference was limited to fewer running wheel revolutions per exercise session, and slower running speed, suggesting a lowered ability to exercise, not lowered desire. 

The findings, published recently in the Journal of Clinical Investigation, demonstrate the benefits of exercise at the molecular level and highlights the crucial link between physical activity, physical performance, and Piezo1.

“Our work sheds new light on how Piezo1’s role in blood vessels is connected to physical activity,” says supervising author Professor David Beech, of the University of Leeds’ School of Medicine. “A lot was already known about its role in blood vessel development, but far less was known about its contribution to vessel maintenance in adults. Our discovery also provides an opportunity to think about how loss of muscle function could be treated in new ways: if we activate Piezo1, it might help to maintain exercise capability.”