The antidote to a bad scrape-up is usually a fairly simple recipe: antibiotics, bandages, and time. Now, a new study suggests that timing also matters. Skin cells that help patch up wounds work more quickly in the daytime than they do at night, thanks to the workings of our circadian clock. The finding suggests patients might recover from injury more quickly if they have surgery during the right time of day.
Biologists and neuroscientists long thought the body’s time keeper, our circadian clock, resided only in the brain. In mammals, that place is a region of the hypothalamus called the suprachiasmatic nucleus, which receives signals from the eyes. However, recent research demonstrated that cells in other parts of the body—including the lungs and liver—keep their own time. Researchers aren’t quite sure how they maintain their own 24-hour schedule, whereas other cells need external reminders.
To find out, John O’Neill, a biologist at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, U.K., and his team studied skin cells known as fibroblasts, which are essential for wound healing. Fibroblasts invade the void left by a scratch and lay the foundation for new skin to grow. The cells are also known to keep their own time. For example, cultured cells exhibit rhythmic oscillations in gene expression where there is no input from the master clock.
Given the fibroblasts’ time-keeping abilities, O’Neill and colleagues searched for proteins within the cells that ebb and flow with daily rhythms. They came back with an unexpected result: Proteins that direct the construction of the cell’s actin-based skeleton worked daytime shifts. These cellular contractors tell fibroblasts to move into an injury to begin the healing process. So the finding suggests that the time of day a wound occurs may affect how quickly it heals. Such a “skyscraper” hypothesis seems reasonable, says Steven Brown, a chronobiologist at the University of Zurich in Switzerland who was not involved in the study. “To build a complex tissue over several days, it makes sense to import building materials in a regularly timed fashion,” he says.
The researchers then tested that hypothesis with cells grown in a flat layer in a petri dish. The fibroblasts filled in scratches more quickly during the day than at night. “You can see by eye, when the cell is wounded only 8 hours apart from each other, in a different circadian phase, the [daytime] wounded ones take off, and the [nighttime] one drags,” O’Neill says.
The researchers then showed in mice that skin wounds suffered during waking hours healed better than ones incurred during resting hours. What’s more, those increases lined up with the cell culture data. About twice as many fibroblasts migrated into the daytime wounds as nighttime ones. “We were really astonished,” O’Neill says.
Finally, O’Neill and colleagues looked for evidence of such an effect in humans. The team examined data from the International Burn Injury Database, which records, among other things, the time of day an injury occurred. The analysis revealed that nighttime burns took an average of 11 days longer to heal than burns incurred during the day, the researchers report today in Science Translational Medicine. Brown calls the findings insightful. “I find it fascinating that even though wound healing takes days, a circadian clock is still used to optimize different aspects of the process.”
O’Neill says that the time-varying response may be an evolutionary adaptation. As people are more likely to sustain injuries when awake than when sleeping, perhaps our bodies are primed to respond more quickly in the daytime. But he emphasizes the need for further controlled clinical studies to confirm the effect. He speculates that, if real, the effect could help people recover more quickly by scheduling surgeries in time with their personal circadian rhythms, earlier for morning larks and later for night owls.
*Update, 13 November, 3:17 p.m.: This story has been updated to include comments from an outside researcher.