New research links body clocks to chronic lung diseases

March 17, 2014 by Kath Paddison, University of Manchester

(Medical Xpress)—The body clock's natural rhythm could be utilized to improve current therapies to delay the onset of chronic lung diseases.

Scientists at The University of Manchester have discovered a rhythmic defence pathway in the lung controlled by our body clocks, which is essential to combat daily exposure to toxins and pollutants.

Internal biological timers (circadian clocks) are found in almost all living things driving diverse processes such as sleep/wake cycles in humans to leaf movement in plants. In mammals including humans, circadian clocks are found in most cells and tissues of the body, and orchestrate in our physiology.

The research team's ground breaking findings, which are being published in Genes & Development, have for the first time found that the in the mouse lung rhythmically switches on and off genes controlling the antioxidant defense pathway. This 24 hourly rhythm enables the lungs to anticipate and withstand daily exposure to pollutants.

The research was led by Dr Qing-Jun Meng from The University of Manchester who is also a Medical Research Council (MRC) Research Fellow. He has been studying body clocks for a number of years and has been awarded an MRC Career Development Award to establish the relationship between the disruption of circadian rhythms and the susceptibility to human diseases, especially those associated with old age.

Dr Meng said: "We used a mouse model that mimics human pulmonary fibrosis, and found that an oxidative and fibrotic challenge delivered to the lungs during the night phase (when mice are active) causes more severe lung damages than the same challenge administered during the day which is a mouse's resting phase."

This means that the rhythm of this lung clock gives an indication of more suitable times of the day for drugs to be administered to patients suffering from oxidative/fibrotic diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease.

Dr Meng continued: "Our findings show that timed administration of the antioxidant compound sulforaphane, effectively attenuates the severity of the lung fibrosis in this mouse model."

In other words the research suggests that taking drug treatments for oxidative and fibrotic diseases according to the lung clock time could increase their effectiveness, which would allow a lower dosage and consequently reduce side effects.

Dr Vanja Pekovic-Vaughan, who was part of the University's research team, said: "This research is the first to show that a functioning clock in the lung is essential to maintain the protective tissue function against oxidative stress and fibrotic challenges. We envisage a scenario whereby chronic rhythm disruption (e.g., during ageing or shift work) may compromise the temporal coordination of the antioxidant pathway, contributing to human disease."

This latest study is part of on-going research that is exploring how chronic disruption to body clocks by changes like ageing or shift work contribute to a number of conditions such as osteoarthritis, cardiovascular disease, breast cancer, and mood disorder.

Dr Meng said: "Our next step is to test our theory that similar rhythmic activity of the antioxidant defence pathway also operates in lungs. This will enable us to translate our findings and identify the proper clock time to treat chronic lung diseases that are known to involve oxidative stress.

"Funded by an MRC Fellowship Partnership Award, we have teamed up with GlaxoSmithKline to explore the potential of utilizing the mechanisms to improve the efficiency of the current antioxidant compounds for diseases. Timing the delivery of drugs - so-called 'chrono-therapy' or 'chrono-pharmacology' - has already demonstrated clinical benefits in treatment of cancer and arthritis," he said.

Professor Stuart Farrow, a Director in the Respiratory therapy area at GSK (who is also the industrial partner for Dr Meng on the MRC Fellowship Partnership Award), commented: "Chronic diseases are prevalent and debilitating, and continue to be an important area of unmet medical need. This exciting new research reveals an opportunity to harness the body clock to provide valuable benefit to patients."

Explore further: New research links body clocks to osteoarthritis

More information: Gossan, Nicole; Zhang, Feng; Guo, Baoqiang; Jin, Ding; Yoshitane, Hikari; Yao, Aiyu; Glossop, Nick; Zhang, Yong Q; Fukada, Yoshitaka; Meng, Qing-Jun. "The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor." N A R, eScholarID:220750

Related Stories

New research links body clocks to osteoarthritis

June 11, 2013
Scheduled exercise, regular meals and the periodic warming and cooling of joints could be used to relieve the symptoms of osteoarthritis according to scientists at The University of Manchester. Their research may also help ...

Want a good night's sleep in the New Year? Quit smoking

January 2, 2014
As if cancer, heart disease and other diseases were not enough motivation to make quitting smoking your New Year's resolution, here's another wake-up call: New research published in the January 2014 issue of The FASEB Journal ...

Researchers discover new way to improve internal clock function

August 21, 2013
Overnight flights across the Atlantic, graveyard shifts, stress-induced insomnia are all prime culprits in keeping us from getting a good night's sleep. Thanks to new research from McGill University and Concordia University, ...

Key protein is linked to circadian clocks, helps regulate metabolism

June 18, 2013
Inside each of us is our own internal timing device. It drives everything from sleep cycles to metabolism, but the inner-workings of this so-called "circadian clock" are complex, and the molecular processes behind it have ...

The internal clock and feeding rhythm set the pace of the liver

January 15, 2014
Living organisms have adapted to the day-night cycle and, in most cases, they have evolved a "circadian clock". Its effects are not completely known yet but its functioning has been shown to have important metabolic consequences ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.