Scientists have discovered that people who regularly sleep for very long (11 hours or more) or very short (four hours or less) periods of time are two to three times more likely to have the incurable disease pulmonary fibrosis, compared to those that sleep for seven hours in a day.
The researchers attribute this association to the body clock. Their study showed that targeting the body clock reduced fibrosis in vitro, revealing a potential target for a disease that kills about 5,000 people a year in the UK.
The research team included members from the Universities of Manchester, Oxford, Newcastle, University College London and Toronto. Among them was Prof David Ray, a principle investigator in the NIHR Oxford BRC’s Diabetes and Metabolism theme.
The study was published in Proceedings of the National Academy of Sciences and was funded by the Medical Research Council and the Wellcome Trust.
Our internal body clocks regulate nearly every cell in our bodies, driving 24-hour cycles in many processes such as sleeping, hormone secretion and metabolism.
In the lungs, the clock is mainly located in the main airways. However, the team discovered that in people with lung fibrosis, these clock oscillations extend out to the small air spaces, called alveoli.
Previous studies in mice have found that by altering the clock mechanism it was possible to disrupt the fibrotic process making the animals more likely to develop pulmonary fibrosis.
Using human data from the UK Biobank, the researchers showed that pulmonary fibrosis is associated with short and long sleep duration. The link between sleep duration and lung fibrosis is similar in strength to other known risk factors for this disease.
People who report they regularly sleep four hours or less in a day doubled their chance of having pulmonary fibrosis, while those sleeping 11 hours or longer a day tripled their chance of having the disease, compared to those sleeping seven hours per day.
Smaller, but still elevated, risks were also seen in people who like to stay up late at night or those who do shift work.
The researchers explained their findings by the discovery of a core clock protein (REVERBα), which alters the production of a key protein in lung fibrosis (collagen). They say this is an exciting finding because chemical compounds can alter the function of REVERBα.
The authors were able to show that one of these REVERBα compounds can reduce collagen in lung slices from people with this disease.
They said that the discovery that the body clock is potentially a key player potentially opens new ways to treat or prevent pulmonary fibrosis, although more needs to be done to study the association between the disease and sleep duration to establish both causation and reproducibility.
If the results are confirmed, then sleeping for the optimal time may reduce the impact of this devastating disease.
Previous studies have shown that the clock also plays an important role in infection, cancer and diabetes. The discovery that the clock plays a role in fibrosis suggests that altering these oscillations could become an important therapeutic approach.