[Reading Science] Found the Cause of Modern People's Chronic Fatigue

US Research Team Identifies Related Functional Protein
Positive Signs for Developing Treatments for Long COVID and More

Chronic fatigue syndrome is a disease that many modern people suffer from. Recently, it has become a serious problem as a type of post-COVID-19 sequela known as Long Covid. However, scientists have identified the causative protein of chronic fatigue syndrome, raising hopes for the development of future treatments.

Chronic fatigue. Reference image.

According to the international academic journal Science, on the 14th (local time), the U.S. National Heart, Lung, and Blood Institute published these research results in the Proceedings of the National Academy of Sciences (PNAS).

The research team initially planned to study mutations in the cancer-triggering gene TP53 in a 38-year-old woman. Unlike her father and brothers, this woman had a mutation in the TP53 gene but had not been officially diagnosed with chronic fatigue syndrome, although she had long complained of severe fatigue. The team aimed to collect samples from her muscle cells to identify abnormalities in biochemical pathways related to TP53. During this process, however, they discovered that the WASF3 protein was abnormally elevated. WASF3 is a type of protein associated with Wiskott-Aldrich syndrome, which causes symptoms such as eczema, thrombocytopenia, and immunodeficiency, and it had already been reported in a 2011 paper to possibly be related to chronic fatigue syndrome.

The research team predicted that WASF3 could cause chronic fatigue syndrome through interactions with mitochondria, the organelles responsible for energy production within cells. They conducted experiments regulating the amount of WASF3 protein in cells collected from the woman, other individuals, and mice, confirming that the protein interferes with mitochondrial function. In particular, high levels of WASF3 prevented mitochondria from assembling into molecular complexes necessary for normal energy production.

Next, the team genetically engineered mice to deliberately increase the amount of WASF3 protein, and these mice also exhibited mitochondrial dysfunction. They suffered from fatigue to the extent that they could only run about half as much on a wheel compared to normal mice. The researchers then turned their attention to humans, collecting muscle cells from 14 individuals officially diagnosed with chronic fatigue syndrome and 10 healthy individuals for examination. The results confirmed that WASF3 levels were significantly higher in the cells of those suffering from chronic fatigue syndrome.

The research team believes that this mechanism could be used to treat people suffering from chronic fatigue and cognitive impairments even after recovering from COVID-19. Since WASF3’s interference with mitochondrial energy production likely affects not only muscle cells but also brain cells, it could be a cause of cognitive impairment. In this case, developing drugs that reduce WASF3 levels could open the way to treating chronic fatigue syndrome and Long Covid symptoms.