New Study Finds Protein That Could Explain Why it is Hard to Exercise After a Long Period of Inactivity

Physical fitness is important for survival. Lack of physical activity results in detraining, lower performance, and ultimately, incapacity. 

Exercise is commonly encouraged, even prescribed, as therapy. We know that if every human could maintain a suitable level of exercise and fitness, many disease problems would be less severe and quality of life would be better.

In a recently published study, researchers from the University of Leeds, United Kingdom, found that Piezo1, a protein found in the inner lining of blood vessels, can detect the rise in blood flow during physical exercise. The research appears in the Journal of Clinical Investigation. 

Study Development and Results

The researchers found that this protein is essential for maintaining the density of capillaries in the muscles and the capacity for physical activity, which suggest that the presence of Piezo1 in blood vessels may modulate the ability for physical performance based on changes in blood flow during exercise. 

The researchers used adult mice that were genetically engineered by disrupting the expression of the Piezo1 gene in their endothelial cells.

They compared the effects of Piezo1 deactivation on physical activity with a control group consisting of adult mice with intact endothelial Piezo1 expression, and found that mice in the Piezo1 deactivation group showed lower running, climbing, and walking levels at 10 weeks than the control group. 

Both groups engaged in physical activity for a similar amount of time. However the Piezo1 deactivation group had lower running speeds, suggesting a negative impact on physical performance without influencing the motivation to engage in physical activity. 

They also 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 data found suggested  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.

The researchers concluded that physical inactivity may result in lower blood flow to the muscles, reduced activation of Piezo1, and subsequently a decline in exercise capacity.


Fiona Bartoli, et al. Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity. J Clin Invest. 2022;132(5):e141775.

Deep Shukla. (2022, Mar 9). Protein may explain why it is harder to exercise after a period of inactivity. Medical News Today. Retrieved from:

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