Posts Tagged ‘sleep’

New Therapy May Reset Biological Clocks

Biological clocks and sleep schedules may be able to be reset through administration of glucocorticoids, opening up new therapeutic avenues for improving the synchronization of the body’s various biological clocks, according to a new study.

Physiological changes over the course of a day are regulated by a circadian system composed of a central clock located deep within the center of the brain and multiple clocks located in different parts of the body.

“These results lead us to believe that we may one day be able to use a combined therapy that targets the central clock (inverting work schedules, administering controlled light therapy) with a pharmacological treatment that targets the peripheral clocks to ensure that all clocks are adjusted,” said lead author Diane B. Boivin, MD, PhD, Professor in the Faculty of Medicine at McGill University and the Founder/Director of the Centre for Study and Treatment of Circadian Rhythms of the Douglas Mental Health University Institute in Montreal.

In previous studies, Dr. Boivin and her team showed that desynchronized circadian clocks disrupt the sleep, performance, and cardiac parameters of night-shift workers.

The researchers also showed that exposing workers to bright light at night or adjusting work schedules can improve the synchronization of the central biological clock to their atypical work schedule.

“A single therapy can’t address the disruptions that occur in all biological clocks,” stated Dr. Boivin.

“For example, when used incorrectly, light therapy can even aggravate the situation.”


Clock genes drive biological clocks, and these genes are active in all body organs.

Animal studies have shown that the central biological clock in the brain sends signals to the clocks in other organs.

Glucocorticoids appear to play a central role in transmitting these signals.

Glucocorticoids, such as cortisol and cortisone, are essential for the utilization of carbohydrate, fat and protein by the body and for normal response to stress.

This is the first study to demonstrate that glucocorticoids play this role in humans, the researchers stated.

They studied the rhythmic expression of clock genes in white blood cells of 16 healthy volunteers to see how the volunteers adjusted to glucocorticoids administered in the late afternoon.

The results show that 20 mg of hydrocortisone taken orally acutely increased gene expression in peripheral blood mononuclear cell (PBMC) peripheral clocks.

After 6 days of hydrocortisone administration, the phases of central markers were not affected; however, expression of 2 genes in PBMCs were shifted by about 9.5 to 11.5 hours.

This suggests that biological rhythms may play a role in controlling immune function in night-shift workers, the investigators stated.


The new research opens the door to innovative therapies that adjust circadian rhythms in inverted sleep schedules, combining synchronizing agents for the central and peripheral clocks.

This has possible applications for travelers, night-shift workers, patients who are experiencing sleep disorders and circadian rhythm disorders, and persons with various psychiatric disorders, they stated.

“At this stage, we are not recommending the use of glucocorticoids to adjust the rhythms of night-shift workers, as there could be medical risks,” Dr Boivin said.

The researchers published their results online December 12, 2014 in The FASEB Journal.

Night Shifts Upset Sleep, Up Heart Death Risk

Night shift work not only disrupts sleep patterns but also increases the risk of cardiovascular disease (CVD) and lung cancer deaths, according to one of the largest prospective cohort studies worldwide with a high proportion of rotating night shift workers and long follow-up time.

“Women working rotating night shifts for more than 5 years have a modest increase in all-cause and CVD mortality.

Those working more than 15 years of rotating night shift work have a modest increase in lung cancer mortality.

These results add to prior evidence of a potentially detrimental effect of rotating night shift work on health and longevity,” report researchers led by Eva S. Schernhammer, MD, DrPH, Associate Professor of Medicine, Harvard Medical School, and Associate Epidemiologist, Department of Medicine, Brigham and Women’s Hospital, Boston.

There is substantial biological evidence that night shift work enhances the development of CVD.

In 2007, the World Health Organization classified night shift work as a probable carcinogen because of circadian disruption.


Sleep and the circadian system play an important role in cardiovascular health and anti-tumor activity.

The circadian system and its prime marker, melatonin, are considered to have anti-tumor effects through multiple pathways — including antioxidant activity, anti-inflammatory effects, and immune enhancement — and they exhibit beneficial actions on cardiovascular health by enhancing endothelial function, maintaining metabolic homeostasis, and reducing inflammation, the researchers noted.

“Direct nocturnal light exposure suppresses melatonin production and resets the timing of the circadian clock,” they stated.

“In addition, sleep disruption may also accentuate the negative effects of night work on health.

Taken together, substantial biological evidence supports the role of night shift work in the development of poor health conditions, including cancer, CVD, and ultimately, mortality.”


Using data from the Nurses’ Health Study, the international team of researchers analyzed 22 years of follow-up of nearly 75,000 women.

Night shift information was collected in 1988.

Rotating shift work was defined as working at least 3 nights per month in addition to days or evenings in that month.

The investigators found that working rotating night shifts for more than 5 years is associated with an increase in all-cause and CVD mortality.

Mortality from all causes appeared to be 11% higher for women with 6 to 14 years or more than 15 years of rotating night shift work.

CVD mortality appeared to be 19% and 23% higher for those groups, respectively.

There was no association between rotating shift work and any cancer mortality, except for lung cancer in those who worked the night shift for 15 or more years (25% higher risk).

“A single occupation (nursing) provides more internal validity than a range of different occupational groups, where the association between shift work and disease outcomes could be confounded by occupational differences,” the researchers noted.

“To derive practical implications for shift workers and their health, the role of duration and intensity of rotating night shift work and the interplay of shift schedules with individual traits (eg, chronotype) warrant further exploration,” they added.

The researchers published their results in the January 5, 2014 issue of the American Journal of Preventive Medicine.