The majority of human cells, including skin and hair cells, keep their own time; that is, they manifest autonomous clocks and the genes that regulate their functioning.1 During the day, one primary function of the skin is protection; at night, repairing any damage (particularly DNA impairment) incurred during the day prevails.2-4 These activities are driven through circadian rhythms using clock genes that exist in all cutaneous cells.2 Important cutaneous functions such as blood flow, transepidermal water loss, and capacitance are affected by circadian rhythms.5 Hydration and inflammation are also among the several functions pertaining to epidermal homeostasis affected by circadian rhythms.6 In addition, some collagens and extracellular matrix proteases are diurnally regulated, and approximately 10% of the transcriptome, including the extracellular matrix, is thought to be controlled by circadian rhythms.7
Cutaneous cell migration and proliferation, wound healing, and tissue vulnerability to harm from UV exposure, oxidative stress, and protease activity, for example, are affected by circadian rhythms, Sherratt et al. noted in suggesting that chronotherapy presents promise for enhancing skin therapy.7 Indeed, recent research has led to the understanding that cutaneous aging, cellular repair, optimal timing for drug delivery to the skin, and skin cancer development are all affected by the chronobiological functioning of the skin.8
We have known for several years that certain types of products should be used at different times of the day. For instance, antioxidants should be used in the morning to protect skin from sun exposure and retinols should be used in the evening because of its induction of light sensitivity. The remainder of this column focuses on research in the last 2 decades that reinforces the notion of circadian rhythms working in the skin, and may alter how we view the timing of skin care. Next month’s column, part two on the circadian rhythms of the skin, will address recent clinical trials and the implications for timing treatments for certain cutaneous conditions.
Emerging data on the circadian rhythms of the skin
In 2001, Le Fur et al. studied the cutaneous circadian rhythms in the facial and forearm skin of eight healthy White women during a 48-hour period. They were able to detect such rhythms in facial sebum excretion, transepidermal water loss (TEWL) in the face and forearm, pH in the face, forearm skin temperature, and forearm capacitance using cosinor or analysis of variance methods. The investigators also observed 8- and 12-hour rhythms in TEWL in both areas, and 12 hours for forearm skin temperature. They verified that such rhythms could be measured and that they vary between skin sites. In addition, they were the first to show that ultradian and/or component rhythms can also be found in TEWL, sebum excretion, and skin temperature.9
A year later, Kawara et al. showed that mRNA of the circadian clock genes Per1, Clock, and bmal1/mop3 are expressed in normal human-cultured keratinocytes and that low-dose UVB down-regulates these genes and changes their express in keratinocyte cell cultures. They concluded that UV targeting of keratinocytes could alter circadian rhythms.10
In 2011, Spörl and colleagues characterized an in vitro functional cell autonomous circadian clock in adult human low calcium temperature keratinocytes, demonstrating that the molecular composition of the keratinocyte clock was comparable with peripheral tissue clocks. Notably, they observed that temperature acts as a robust time cue for epidermal traits, such as cholesterol homeostasis and differentiation.11
The next year, Sandu et al. investigated the kinetics of clock gene expression in epidermal and dermal cells collected from the same donor and compared their characteristics. They were able to reveal the presence of functional circadian machinery in primary cultures of fibroblasts, keratinocytes, and melanocytes, with oscillators identified in all skin cell types and thought to be involved in spurring cutaneous rhythmic functions as they exhibited discrete periods and phase relationships between clock genes.12
Three years later, Sandu et al. characterized the circadian clocks in rat skin and dermal fibroblasts. They found that skin has a self-sustaining circadian clock that experiences age-dependent alterations, and that dermal fibroblasts manifest circadian rhythms that can be modulated by endogenous (e.g., melatonin) and exogenous (e.g., temperature) influences.13
In 2019, Park et al. demonstrated that the diurnal expression of the gene TIMP3, which is thought to evince a circadian rhythm in synchronized human keratinocytes, experiences disruptions in such rhythms by UVB exposure. The inflammation that results can be blocked, they argued, by recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients, such as green tea extracts.6
Circadian rhythms and the biological clocks by which most cells, including skin and hair cells, regulate themselves represent a ripe and fascinating area of research. Applying evidence in this realm to skin care has been occurring over time and is likely to enhance our practice even more as we continue to elucidate the behavior of cutaneous cells based on the solar day. Based on this information, my recommendations are to use antioxidants and protective products in the morning, and use DNA repair enzymes, retinoids, and other repair products at night.
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 , a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at .
1. Dong K et al. Int J Mol Sci. 2020 Jan 3..
2. Dong K et al..
3. Lyons AB et al..
4. Wu G et al..
5. Vaughn AR et al..
6. Park S et al. Int J Mol Sci. 2019 Feb 16..
7. Sherratt MJ et al..
8. Luber AJ et al..
9. Le Fur I et al..
10. Kawara S et al..
11. Spörl F et al..
12. Sandu C et al..
13. Sandu C et al..