Daytime wounds may heal faster

"Daytime wounds 'heal more quickly'," reports BBC News. Researchers discovered that skin cells' internal clocks allow them to respond more quickly to an injury inflicted when they are usually active, than during usual rest times.

The findings are in line with UK figures that show people who sustained burns injuries during the daytime healed more quickly than those injured at night.

The researchers carried out a series of experiments on skin cells, some from mice and some from humans. They looked at whether fibroblasts changed activity according to circadian rhythm (our internal body clock).

Fibroblasts, described in the media as the body's "first responders", are specialist cells that help repair damaged tissue.

The internal body clock regulates temperature and hormone activity. Feedback from this body clock is received by every cell in the body, which then synchronise to set their own cellular clocks.

The results of the experiments suggest fibroblasts can move more quickly to the site of a wound during daytime.

However, the findings don't prove that night time burns victims healed less quickly because of their body clock. It's possible, for example, that people burned at night had more severe burns, because they were asleep when fire broke out, or that it took longer for them to get treatment than it would have done during the day.

The researchers speculate that we may be able to take advantage of this effect. For example, some forms of steroid cream are also known to "reset" circadian rhythm at a cellular level, which may be beneficial for wound healing. However, more work is needed to show that this type of approach would be safe or beneficial.

Where did the story come from?

The study was carried out by researchers at the Medical Research Council's Laboratory of Molecular Biology, Addenbrooke's Hospital and the University of Manchester, all in the UK. It was funded by the Medical Research Council and the Wellcome Trust. The study was published in the peer-reviewed journal Science Translational Medicine.

The UK media reports mainly focused on the figures for healing of burns victims, and they did not question or explore alternative reasons why healing might be quicker for those injured during the day.

The reporting also gave the impression that this research into burn victims was an ongoing project when in fact it was a retrospective analysis of existing data. The distinction is important as retrospective research may carry a higher risk of bias (as you known what patterns you are looking for).

What kind of research was this?

The main part of the research was a series of experiments on mouse skin cells, to observe changes that take place in the cells during 24 hour cycles. The researchers also experimented on live mice, to see how quickly they healed from skin wounds. Finally, they carried out an observational study of people on a burns database in the UK.

Research on animals and on cultured cells can help us understand biological processes, but we cannot be sure that the findings translate to humans. Observational research can help us spot patterns, but it cannot show that one factor (such as time of wounding) directly causes another (such as time taken to heal).

What did the research involve?

The researchers started with a series of experiments on a type of mouse skin cell (fibroblasts) grown in the laboratory. They observed changes to the cells over a 24-hour period, including production of proteins and the forms of a key protein called actin. They also looked at what happened when layers of skin cells were damaged at different times of the day.

They then looked at whether these results applied when they made cuts in the skin of live mice, either during their resting or active phase. They also looked at what happened to layers of human skin cells called keratinocyte that were cultured in a laboratory setting.

Finally, they examined wound time healing data from a UK database of burn injuries. They looked to see whether there was a difference in time to 95% healing of wounds, by the time of day at which the injury had occurred. Usually, researchers would also look at potential confounding factors, such as severity of wound or time to treatment, but the report does not say whether that happened in this case.

What were the basic results?

Experiments on skin cells showed:

• cells produced proteins in different amounts at different times of the day, in line with circadian rhythms
• the protein actin, responsible for cell movement, changed form according to circadian rhythms – but in cells which had been genetically altered to remove their cellular clock, actin did not vary by circadian rhythm
• layers of fibroblasts healed more quickly when injured at peak activity time than at their least active time
• fibroblasts moved faster to wound sites during the peak activity time

Experiments on mice backed up these findings – mice wounded during their active period healed more quickly than those wounded during their rest period. These experiments also showed more collagen was deposited at wound sites in animals wounded during their active period.

The figures from burns units, based on 118 people showed:

• people who’d been wounded between 8am and 8pm were 95% healed after 17 days on average
• people who’d been wounded between 8pm and 8am were 95% healed after 28 days on average
• the quickest wound healing followed wounds made between 8am and 12 noon, and the slowest following wounds between midnight and 4am

How did the researchers interpret the results?

The researchers said they demonstrated how internal cell clocks affect the activity of fibroblasts and actin in the event of an injury. They say more work needs to be done to back up their initial findings in humans.

However, they say: "we speculate that maximal healing could be promoted by pharmacological resetting of local cellular clocks before surgery", by use of drugs that affect the body clock.

Conclusion

This research adds to scientists’ understanding of the skin’s healing processes, and how they may be affected by circadian rhythms.

There is currently a lot of interest in how these "internal clocks" affect our bodies (see our recent story about how this affects digestion). This may be more important now that many people work night shifts, travel frequently across time zones, or simply ignore day and night time because of the easy availability of light and 24-hour entertainment.

However, the study is less conclusive in its findings about healing times for human burns patients. While the time to healing is strikingly different between those injured at day or night, we don’t know what other factors might have caused these differences. The study doesn’t give us enough information to say whether different healing times are affected by body clocks.