Wounds healed nearly 60% faster for injuries occurring during the day rather than at night
Afternoon surgery patients had a 50% lower risk than morning patients of a cardiac event
Circadian rhythms control your sleep and wake cycles as well as guide essential bodily functions including metabolism, blood pressure and even the individual cell-level work done by your genes.
In fact, each of your cells has its own biological clock, which is synchronized via temperature, hormones and other bodily cues, while the entire clockwork symphony is coordinated by a single conductor, a master clock in your brain known as the hypothalamic suprachiasmatic nuclei.
A Nobel Prize awarded to three American scientists who focused their research on the genetic and molecular biology of circadian rhythms suggests how fundamental these processes are to our health. Alina Patke, a research associate in the lab of Dr. Michael Young, one of the Nobel Prize winners and a professor at Rockefeller University, explained that circadian rhythms not only control human behavior and physiology but also that of animals, plants and even fungi.
Recently scientists have begun to wonder if the opposite might also be true: Could healing be guided by this clockwork as well?
Two new studies support this idea, widening our perspective and encouraging us to consider timing as essential to the process of recovery.
Timing of injury
Wounds, such as burns and cuts, heal nearly 60% faster when the injury occurs during the day rather than at night, a new study published Wednesday in Science Translational Medicine found. Scientists from the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, analyzed the records of 118 burn injury patients who had been cared for in England and Wales.
They found burns that happened at night (between 8pm and 8am) took longer to heal than burns that occurred during the day (between 8am and 8pm), the researchers found – an average of 28 days compared to only 17 days.
One reason for this faster daytime healing was that skin cells moved much more quickly to repair the wound site when the body clock was set for daylight, the team said. Within individual cells, this speed was driven by increased activity of proteins that are involved in cell movement and repair.
Mouse experiments, where the researchers made incisions to the skin, also showed wound healing to be significantly greater when wounds were inflicted during the animal’s active phase compared with the rest phase.
Further examining this process in the lab, the researchers “found that the microscopic architecture of the cell, the actin cytoskeleton, has a 24-hour rhythm in skin cells grown in a dish,” said Ned Hoyle, lead author of the paper and a postdoctoral fellow at the MRC Laboratory.
“One of the main jobs of these cells in a whole animal is to respond to wounds by moving into them and secreting proteins to repair the damage,” said Hoyle.
The researchers believe this healing process is driven by individual cells’ internal circadian clocks – and not signals transmitted throughout the body.
Hoyle also speculated that cellular clocks at the site of surgery could be “adjusted to the best time for healing before the operation,” while more generally, “the time of surgery could be scheduled to coincide with each patient’s biological time.” So that “larks,” or early risers, could see the surgeon in the morning, while “owls,” or late risers, would be treated in the afternoon.
Another new study, published last month in the Lancet, also suggests that timing may be essential to health care.
Timing of heart surgery
Following open heart surgery, some patients experience cardiac events that negatively impact the results and increase their risk of dying. The Lancet study explored whether this poor outcome might be influenced by the time of day an operation occurred.
Dr. David Montaigne – the study’s lead author and a professor at University of Lille in France – and his colleagues examined the medical records of 596 people who had heart valve replacement surgery between January 2009 and December 2015. Half of the patients had surgery in the morning, half in the afternoon.
People who had surgery in the afternoon had a 50% lower risk of a major cardiac event within 500 days of their operation compared to people who had surgery in the morning, the researchers found. Among the 298 afternoon patients, 28 had an event (9.4%) compared to 54 of 298 morning patients (18.1%).
Next, with the help of surgical patients, the researchers conducted an additional experiment between January 2016 and February 2017. Montaigne and his colleagues randomly scheduled half of 88 patients for heart valve replacement surgery in the morning and the other half for an afternoon operation and then monitored all until they left the hospital.
None of the patients died, and the average hospital stay was the same for both groups: 12 days.
Still, afternoon surgery patients had lower levels of heart tissue damage after surgery compared to the morning group, the researchers found. Conducting genetic tests on tissue samples, the team learned that the 287 genes linked to the circadian clock were more active in the afternoon samples than the morning samples. And in experiments on mice involving the deletion and replacement of relevant genes, the researchers found more evidence to suggest the heart’s ability to repair in the morning is poorer than in the afternoon.
Based on their explorations, the team believe drugs could be developed to modulate these genes and so protect the heart during surgery. Or, surgeries can be scheduled to protect at-risk patients.
“Aortic valve replacement is very safe nowadays,” said Montaigne and his co-author, Bart Staels, a professor at the University of Lille said by email. “The point is not to alter the schedule of surgery for all patients: changing the time of surgery for low risk patients (the most abundant) makes no sense, since they do not develop complications.”
Montaigne and Staels emphasized that more research is needed. Still, they noted their “findings are in line with the concepts of chronobiology and chronotherapy” – natural cycle-based biology and treatments.
And there are other examples as well. The existence of daytime variation in chemotherapy efficiency and toxicity has been well known for many years. And more recent experiments have shown that morning vaccination with a flu shot enhances immune response more than afternoon vaccination.
Join the conversation
On a lighter note, Hoyle said the practical applications of the new research might one day include a cure for jet lag.
But it’s more than just sleeping patterns that are affected. Patke noted that circadian dysfunction is also a medical issue.
“How this actually works is not entirely clear,” she said. “But most people would agree at this point that there definitely is a correlation.”