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Protein may explain why it is harder to exercise after a period of inactivity

Periods of physical inactivity due to a sedentary lifestyle, illness, or injury are associated with reduced ability for physical exercise, or detraining.

A recent study in mice suggests that the Piezo1 protein expressed by endothelial cells lining the inner surface of blood vessels could mediate these effects of physical inactivity on exercise capacity.

Previous researchTrusted Source has shown that the endothelial Piezo1 protein can detect changes in blood flow during physical activity. The present study found that the deactivation of Piezo1 resulted in a reduced density of capillaries in the muscle and a decline in the capacity for physical activity.

These data suggest that Piezo1 can modulate the local blood supply to muscles and thus physical performance capacity according to physical activity levels.

The study’s co-author Dr. Fiona Bartoli, a postdoctoral fellow at the University of Leeds, United Kingdom, told Medical News Today: “Although this study was performed in mice, the Piezo1 protein is also present in humans, indicating that the same molecular mechanism could exist. We suggest that deactivating Piezo1 by not doing enough exercise impacts physical performance by reducing the capillary density in muscles.”

“This restricted blood flow means activity becomes more difficult, causing further inactivity and leading to a downward spiral. It helps to explain the biology of why exercise becomes harder the less you do and why it is important to exercise regularly to keep our Piezo1 proteins active to maintain our physical performance and health.”

– Dr. Bartoli

The study appears in the Journal of Clinical Investigation.

Physical activity and Piezo1

Scientists have speculated for some time now that certain molecules in the body may be able to detect physical activity levels and help the body adapt as the levels of physical activity change.

Physical activity is associated with an increase in blood flow to the muscles. Thus, molecules capable of detecting changes in blood flow to the muscles could serve as exercise sensors.

The endotheliumTrusted Source is a layer of cells that forms the innermost surface of blood vessels and can detect changes in blood flow.

Recent studies have shown that the Piezo1 protein expressed by endothelial cells can sense the increase in blood flow during physical activity. Moreover, the Piezo1 protein is also essentialTrusted Source for enhancing blood flow to the muscles during physical activity.

However, the impact of Piezo1 on physical activity levels remains unclear. Researchers undertook the present study to examine the ability of Piezo1 to modulate physical activity levels.

Reduced physical activity

In the present study, the researchers used adult mice that they had genetically engineered by disrupting the expression of the Piezo1 gene in their endothelial cells. Deactivating Piezo1 in adult mice helped the researchers avoid any potentially harmful effects that disrupting this protein might have had in developing mice.

They compared the effects of Piezo1 deactivation on physical activity with a control group consisting of adult mice with intact endothelial Piezo1 expression.

The researchers found that mice in the Piezo1 deactivation group showed lower running, climbing, and walking levels at 10 weeks than the control group.

Although animals in both groups engaged in physical activity for a similar amount of time, Piezo1 deactivation led to lower running speeds, suggesting a decline in the capacity for physical activity.

These data suggest that Piezo1 deactivation had a negative impact on physical performance without influencing the motivation to engage in physical activity.

Underlying mechanisms

Changes in respiration, metabolism, heart function, or muscle composition could potentially explain the decline in physical performance after Piezo1 deactivation.

The researchers found that Piezo1 deactivation did not alter energy metabolism, respiratory or cardiac function. Similarly, animals in the experimental and control groups did not differ in skeletal muscleTrusted Source mass or the composition of muscle fibers, both of which can influence physical performance.

Subsequently, the researchers examined the impact of Piezo1 disruption on the density of capillaries in the skeletal muscle. They found that Piezo1 deactivation reduced capillary density in muscles by 20%. Moreover, such a reduction in capillary density was absent in cardiac tissue, suggesting that the effects of Piezo1 deactivation were specific to the skeletal muscle tissue.

The researchers then examined if the reduced capillary density in skeletal muscle tissue after Piezo1 deactivation was due to the regression of previously existing blood vessels. The endothelial cells in the blood vessels are supported by a matrix called the vascular basement membrane.

After deactivation of Piezo1, the researchers found remnants of previously existing capillaries in the form of the vascular basement membrane without attached endothelial cells in skeletal muscle.

They also identified an upregulation of markers for cell death in endothelial cells after Piezo1 deactivation.

These data suggest that the reduced capillary density in skeletal muscle tissue after Piezo1 deactivation was due to increased death of endothelial cells, resulting in regression of blood vessels.

According to a model based on these data, the increased blood flow during physical activity may activate the endothelial Piezo1 protein. This activation may help maintain or increase the stability of blood vessels in skeletal muscle tissue, thus increasing capillary density and improving muscle performance.

In the present study, the disruption of Piezo1 gene expression in genetically modified mice resulted in lower physical activity levels and reduced capillary density in the skeletal muscle tissue.

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