2024-02-10 18:04:41
Chronic disruption of the day-night rhythm is carcinogenic. Researchers demonstrate this with an experimental model that combines human and mouse liver cells. The humanized mice with jet lags developed liver cancer faster and more often, which can be translated to humans.
Anyone who has ever flown to the other hemisphere has undoubtedly suffered from jet lag: a disturbed day-night rhythm caused by the time difference. You are tired, cannot sleep well and with a bit of bad luck you also have stomach and intestinal complaints. Although it seems quite harmless, chronic jet lag (where your day-night rhythm is regularly disrupted) can cause serious health problems. Researchers have that Baylor College of Medicine demonstrated by their research. They did this by disrupting the internal clocks of mice that partly contain human liver cells and seeing what effects this had on the mice’s bodies.
We know that our internal biological clock plays an important role in the functioning of our body. It coordinates when you get hungry, tired or need to be alert. This clock is largely influenced by daylight, which means that our day-night rhythm contains cycles of 24 hours. Recent studies have shown that when the internal clock is no longer synchronized, diseases are more likely to develop. Epidemiological studies even found a link between chronic jet lag and an increased risk of liver cancer. However, experimental evidence for this was lacking until now.
Mouse model with human liver cells
The researchers worked with a so-called ‘humanized’ mouse model. “This animal model has both human and mouse liver cells in the animals’ livers,” explains lead author Loning Fu. “This allows us to study the effect of disrupting the day-night rhythm on the development of cancer in human cells.”
Flying up and down every week
The humanized mice were exposed to two different conditions. One group continued to follow the natural day and night cycle. So they got normal amounts of light and dark hours in a day. In the other group, the researchers manually adjusted the periods of light and dark. They created the equivalent of the changes a person experiences when flying back and forth from San Francisco to London every week. And that for weeks.
The consequences of chronic jet lag for the liver
“We found that mice in the jet lag group had a shorter lifespan and also developed more fatty liver disease, jaundice and cancer,” Fu said. Not only in the liver cells from the mouse itself, but also in human liver cells. The latter is especially important, he emphasizes. The blood analyzes and microscopic examinations of the livers showed several similarities between the livers of the humanized mice and patients with liver cancer. Glucose intolerance, for example, but also abnormal fat accumulation in the liver, inflammation and fibrosis.
Awareness and prevention
So the chronic jet lag humanized mice not only developed cancer faster and more often than the other mice. But the liver cancer in their human liver cells also followed the same process and via the same molecular pathways as happens in people with liver cancer. This indicates that this mouse model is valid as a model for studying the human situation, and that the findings of the research can be reliably translated to humans.
The researchers hope that their research can raise awareness of the dangers of chronic jet lag. They emphasize that this knowledge is not only relevant for people who travel often. People who work shifts or who have irregular sleep patterns may also be at greater risk of liver cancer.
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