Understanding the skin’s circadian rhythm and metabolome

By Yeji Hong

Circadian rhythms, which are 24-hour oscillations in behaviour and physiology, play a role in the function of all cells in the body to optimize cellular functions to adapt to environmental challenges throughout the day. Visible light is considered as the most powerful ‘master’ clock to act upon humans, through the retina. The master clock coordinates circadian expression of tissue-specific output genes and controls the rhythmic expression of target genes.

Previous studies have demonstrated that up to 10% of gene expression in any tissue is rhythmical, and there is tissue-specific circadian control of various mechanisms such as cell growth, DNA damage-repair responses, metabolic processes and immune function (Matsui et al., 2016).

To better understand the link between the circadian rhythm and the cellular mechanisms in skin, a study was carried out by researchers at Estee Lauder, where they investigated the metabolome of skin from young people aged 20~25 and from older people aged 60. In this unpublished study, by sampling their skin surface early in the morning and late in the evening, they obtained metabolomic profiles at the skin surface. A non-invasive sampling strips collection method was utilised, a novel and useful in vivo sampling which provides the ability to view complex patterns to identify the changes that happen to the skin throughout the day. The metabolites were isolated from the individuals and subjected to metabolic profiling using a multi-method liquid chromatography with tandem mass spectrometry platform (Corallo et al., 2019). 

Through studying metabolomics, the researchers focused on finding a more direct link to phenotype as metabolomics takes into account the influence that the environment has on the behaviour of skin. This was crucial, as external factors such as exposure to sunlight or pollution have been found to have the ability to affect skin as much as genes. Their findings showed that over 300 metabolites contributed to the appearance of skin, and out of these, 220 metabolites were found to change with age. Young and healthy skin metabolites follow a circadian rhythm, leading to completely different metabolite profiles in the morning and in the evening. They found that 186 of metabolites follow a distinct circadian rhythm in young skin but only 44 of these retain the rhythm in mature skin. The 186 metabolites that follow a rhythm in youthful skin were classified into several categories: oxidative damage, inflammation, protein breakdown and barrier integrity/moisturization. 

Oxidative damage, which is caused by an imbalance in antioxidants and free radicals in the body, was found to be low in the morning and increase over the course of the day. Healthy young skin was able to efficiently repair the damage each night for healthy young skin, but in mature skin, the oxidative damage was found to increase and show a poor repair efficiency. Inflammation was found to lower in the morning and increase through the day in young skin but was much higher and in a constant state in mature skin, translating into increased damage and loss of repair abilities. Protein damage was repaired overnight effectively in young skin, but in mature skin, the extent of damage was higher throughout the day and the repair was less effective, leading to an accumulation of protein damage and skin mechanical properties. Furthermore, skin barrier integrity was highest in the morning for young skin, and metabolites associated with lack of differentiation and lower moisturization were at their lowest, suggesting that differentiation had occurred and completed overnight to build a strong barrier. However, in mature skin, the levels of these metabolites were much higher, indicating an impairment in barrier integrity.

This study was able to establish that metabolite profiles show cycles of protection and repair to adapt to the environment depending on the circadian rhythm; during the daytime, it maximises skin protection to prevent damage from sun exposure and during the evening it engages in repair and recovery. Studies such as these acts as an important connector between skincare and technology and opens up a possibility for a technology designed to direct the timing of specific cellular functions and key metabolites to help re-establish the skin’s ideal rhythm for maintaining skin health even with age. This also opens up a future for skincare professionals to customize treatment options based on an individual’s skin metabolome and the possibility of defining metabolic profiles associated with common skin problems, including acne, sensitive skin and dry skin (Pernodet et al., 2019).


Matsui M.S., Pelle E., Dong K., Pernodet N. (2016) Biological Rhythms in the Skin. International Journal of Molecular Sciences. Available from: doi: 10.3390/ijms17060801

Corallo K., Pelle E., Feld G.K., Beebe K., Teng F., Evans A., Pernodet N. (2019) First Assessment of Facial Skin Circadian Metabolomics on Young and Aging Subjects in vivo. Available from: https://cdn2.hubspot.net/hubfs/5084876/Poster/WCD2019-%20final%20assessment%20of%20skin%20metabolomics.pdf 

Pernodet N., Sassone-Corsi P. (2019) Metabolomics Highlights: The Importance of Circadian Rhythm in Skin. Practical Dermatology. Available from: https://practicaldermatology.com/articles/2019-oct/metabolomics-highlights-the-importance-of-circadian-rhythm-in-skin/pdf 

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