Cosmeceutical Critique

Circadian rhythms, part 2: Can treating cutaneous conditions at different times of the day improve outcomes?


 

We continue with a focus on circadian rhythms and implications for skin care this month, paying particular attention to research or insights pertaining to specific skin conditions, when possible, as well as clinical studies that may shed light on how to time skin care treatments.

Vectorial illustration of a clock with human hands, representing the circadian rhythm of sleep and wakefulness. In the balanced cycle, a half circle contains the night and the other one the day. Francesca Bellini/iStock/Getty Images

It is important to remember that several studies in the last 20 years have revealed cutaneous tendencies based on the time of day. For instance, sebum production is known to be highest around noon, and pH also peaks during the day and is at its lowest at night.1-5

Skin aging

In 2019, Dong and associates showed that blue light at 410 nm reduces PER1 transcription in keratinocytes, indicating that epidermal cells have the capacity to directly sense light and regulate their own clock gene expression. With the introduction of blue light at night, circadian rhythm is disrupted as epidermal skin cells act as if it is daytime. The investigators also considered blue light–induced damage to skin cells at various doses and exposure times in comparison with cells that remained unexposed to light. The production of reactive oxygen species increased in the exposed cells, as did DNA impairment and the emergence of inflammatory mediators, all of which have the potential to hasten aging.6

Early this year, Dong and associates demonstrated that melatonin can dose-dependently stimulate PER1 clock gene expression in normal human dermal fibroblasts and normal human epidermal keratinocytes, and verified that the MT-1 melatonin receptor in such fibroblasts manifests a marked decline with age. The researchers concluded that the melatonin pathway contributes significantly in cutaneous aging and impairment, and that its relationship with skin circadian rhythm points to a possible role in slowing the rate of skin aging through the modulation of cutaneous melatonin receptors.7

Wound healing

In 2019, Walker and associates investigated the effects of dim artificial light at night on wound healing in female C57BL/6 mice, and found that those conditions prior to wounding reduced healing. They concluded that such information might warrant consideration in prescribing treatment.8

Atopic dermatitis

Vaughn and associates contended that alterations in circadian rhythm may contribute to the development of atopic dermatitis.9 A good example of the impact of circadian rhythms on cutaneous health is the nocturnal exacerbation of atopic dermatitis, particularly in children.10

Psoriasis

According to Plikus and associates, recent evidence has emerged showing that the circadian clock regulates UVB-induced DNA damage and cutaneous cancers, and it is also associated with the immune-mediated disorder psoriasis.11

Clinical studies

In 2018, Deshayes and associates conducted a clinical study to evaluate the precursors and stem cell attributes of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) in response to clock pathway changes caused by long-term deregulation of circadian rhythms. A total of 20 women participated in the study, 10 in each group (day workers were the control group and compared with shift workers). Two 3-mm fresh punch biopsies were collected from the occipital region of each participant. The investigators reported that chronic circadian rhythm deregulation influenced clock pathway protein expression and correlated with changes in hHF, hEpi, and hHFDP. They concluded that their findings represented the first data in humans suggesting that deregulation of the clock pathway modulates regenerative activity in human cutaneous and hair precursor cells.12

Dr. Leslie S. Baumann, a dermatologist, researcher, author, and entrepreneur who practices in Miami.

Dr. Leslie S. Baumann

Later that year, Wu and associates reported on the role of the circadian clock in the transcriptional regulation of human epidermis. Investigators sampled 20 human participants through a 24-hour period and a population of 219 people once, finding a potent circadian oscillator in human epidermis at the population level, hundreds of rhythmically expressed genes, as well as a biomarker set for human epidermis that can, with one sample, highlight circadian phase within a 3-hour time frame. The team concluded that rhythms in human epidermis persist at the population level, and that they were able to present an effective single-sample circadian biomarker.13 This is important, as Morris pointed out, because the standard practice for measuring an individual’s internal clock is to use a dim-light melatonin onset assay over the course of a day.14 In 2019, Jia and associates studied the skin surface lipid profiles of young women to evaluate and characterize circadian human facial surface lipid composition. The investigators identified significant markers of circadian rhythm, with glycerolipids most affected. They ascribed changes in skin barrier function, such as variable pH and transepidermal water loss, to alterations in triacylglycerol levels as well as free fatty acid chain lengths and content that were affected by variations in circadian rhythm.15

Sleep and the timing of topicals

Based on their recent review of the literature on circadian rhythm and skin, Lyons and associates argued that an understanding of circadian rhythm helps dermatologists in recommending the optimal times for patients to apply topical medications. They added that urging patients to get sufficient sleep is important because DNA repair of the skin occurs best at that time.16

Conclusions

Doctors have known for half a century that timing drug delivery to a patient’s circadian clock can enhance outcomes. Chronobiological research into how circadian rhythms work at the cellular level, and in cutaneous cells in particular, is a fascinating and expanding area of inquiry that could help dermatologists more accurately recommend timing for skin care regimens. Much more research, especially in clinical trials, is necessary to further elucidate how to best work with the skin’s natural rhythms.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on skin care technologies. Write to her at [email protected]

References

1. Mehling A et al. Skin Pharmacol Physiol. 2006;19(4):182-9.

2. Latreille J et al. Skin Pharmacol Physiol. 2004 May-Jun;17(3):133-40.

3. Le Fur I et al. J Invest Dermatol. 2001 Sep;117(3):718-24.

4. Verschoore M et al. Chronobiol Int. 1993 Oct;10(5):349-59.

5. Yosipovitch G et al. J Invest Dermatol. 1998 Jan;110(1):20-3.

6. Dong K et al. Int J Cosmet Sci. 2019 Dec;41(6):558-62.

7. Dong K et al. Int J Mol Sci. 2020 Jan 3;21(1):326.

8. Walker WH II et al. Arch Dermatol Res. 2019 Sep;311(7):573-6.

9. Vaughn AR et al. Pediatr Dermatol. 2018 Jan;35(1):152-7.

10. Fishbein AB et al. J Allergy Clin Immunol. 2015 Nov;136(5):1170-7.

11. Plikus MV et al. J Biol Rhythms. 2015 Jun;30(3):163-82.

12. Deshayes N et al. Eur J Dermatol. 2018 Aug 1;28(4):467-75.

13. Wu G et al. Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-8.

14. Morris A. Nat Rev Endocrinol. 2018 Dec;15(1):3.

15. Jia Y et al. Exp Dermatol. 2019 Jul;28(7):858-62.

16. Lyons AB et al. J Clin Aesthet Dermatol. 2019 Sep;12(9):42-5.

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