As the Earth’s rotation creates alternating hours of light and dark, we adapt our behaviors to harmonize with this daily cycle. An internal ‘clock’ adjusts our metabolism to fit the demands of our usual daytime and nighttime activities. This makes good sense, since our metabolic needs are very different when we are sleeping and fasting, in comparison to what we need when awake, working and eating. Until recently, it was believed that this biological clock resided solely in the brain – in the hypothalamus to be precise – and that the effects of this clock on our metabolism were mediated by hormones, like melatonin and cortisol. In this traditional scheme, light entering the eye, stimulates the retina, transmitting messages along the optic nerve to regulate the activity of the cells in this central clock and their output of these hormones or their activators. That is still true – but it’s not the whole story.
Skin Can Tell Time, Too!
It turns out that nearly all cells have clocks of their own, and melatonin and cortisol released by a central clock are not the only signals to which these ‘peripheral’ clocks are tuned. Now, recent research suggests that the skin may provide the key to understanding our daily or ‘circadian’ rhythms and their importance in medical practice. Epidermis, these authors demonstrate, may be the ideal tissue to study. It possesses a robust peripheral clock, with a set of metabolic pathways having a reliable, diurnal cycle of activity – and it has the added advantage of being readily accessible.
Why is this potentially important? First, in the past physicians could evaluate the timing of a patient’s internal clock only by using difficult to administer and time-consuming assays of blood melatonin levels under standardized laboratory conditions. These assays were not practical for use in clinical settings. But, if Wu, et al, are correct, it should soon be possible to assess the status of a person’s internal clock with a single, easily obtained skin samples, such as plucked hairs or tape-stripped skin.
When Should I Take My Pills, Doctor? Have That Operation? Apply My Creams?
Information about the timing of our internal clocks could be helpful to our doctors, when they prescribe medications or schedule surgery. Other research has shown that ‘circadian’ fluctuations in metabolism impact both the effectiveness of some medications, and the outcomes of surgery. Knowing the status of a patient’s clock might be particularly important for night shift workers, in whom the normal circadian rhythm may well be disrupted. By assessing his or her skin’s clock, physicians might be able to ascertain the best time of day (or night) for a night-time worker to take medications or undergo surgery
The skin’s clock also regulates the repair mechanisms that protect against the development of the types of DNA damage from ultraviolet light linked to skin cancers. Knowing which hours of sunlight are the most risky for producing unrepaired genetic damages that could result in skin cancer for a patient, could help their dermatologist identify the best time for their light treatments – to achieve the desired therapeutic effect with the lowest risk of inducing cancer later on. Our skin’s clock also regulates melanin synthesis – the protein in skin that produces our shades of color. Timing treatments for vitiligo, (a common skin condition of decreased skin pigmentation), around the hours when melanin synthesis is peaking might increase the effectiveness of these therapies. In addition, the knowledge that these clock genes regulate pigment production could lead to new approaches to therapy for this and other pigmentation disorders. Hair is another skin product whose growth is tuned to its biological clock. Clearly, further understanding of the skin’s clocking system may have important therapeutic spin-offs for a variety of skin conditions.
Fourth, and of particular interest to our readers, is the fact that circadian rhythms are also known to modify the efficiency of our skin’s permeability barrier. Knowledge of the timing of a patient’s clock might be predictive of the best time to apply certain topical medications. If the desired effect of the drug requires it to penetrate the permeability barrier, then it might be optimal to apply it when the barrier is less efficient in keeping out foreign chemicals. Conversely, if the benefit takes place on the surface of the skin – as with topical medications directed against ectoparasites, like lice or scabies – then applying the treatment when the barrier is most robust could prevent unwanted side effects, such as neurotoxicity from the scabicide, lindane.
Our Smart Skin
This developing story of the skin’s biological clock can serve as yet another reminder that we should take the skin and what it does for us seriously. In addition, discovery of the skin’s internal clock offers yet another striking example of how the brain and epidermis are closely related, operationally. We now have learned that the skin has retained its own internal clock, which operates in synchrony and employs some of the same genes that regulate the brain’s clock. This should not be surprising if we recall that the brain and epidermis share a mutual embryonic origin. Both are branches from the same tree.