Skin Aging

Figure 1: Hormonal Pauses-hormones that decline with increased age. 

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Skin’s Circadian Rhythm

 The body’s circadian rhythm is well-known for impacting many aspects of health, especially sleep. However, the skin also exhibits a circadian rhythm, resulting in the synchronization of various skin cell types with each other as well as other parts of the body. Some examples include (3):

• Absorption of drugs is highest in the skin at 4 am.

• Skin and core body temperature is lowest in the early morning hours, peak midafternoon and decreases again in the evening.

• Genes regulating keratinocytes are expressed in the late night and early morning hours, resulting in skin barrier recovery being most active in the morning.

• Genes regulating cells of the basal lamina are expressed in the later afternoon and evening, resulting in the skin barrier being the most hydrated and the strongest in the afternoon.

Melatonin for Healthy Skin Aging

As an adjunct to its well-known role in sleep, melatonin has been seen as a prominent cellular guard against oxidative stress, specifically linked to the redox status of cells and tissues. In fact, it has been suggested to be one of the most potent antioxidants because of its ability to scavenge up to 10 reactive oxygen (ROS) and nitrogen species (RNS) with its metabolites compared with most antioxidants, which may only be able to quench a few ROS (3–6).

In skin cells, melatonin is metabolized through 6-hydroxylation, indolic and kynurenic pathways, and through phototransformation (induced by UVB, UVA, and oxidative species) (1). The melatoninergic anti-oxidative systems (MAS) of the skin describe the exposure to UVB which induces melatonin metabolism, leading to antioxidant metabolites in keratinocytes and further antioxidant activity (1).

Of its many functions, melatonin is a known antioxidant, anti-inflammatory agent, and mitochondrial regulator (3,7). In the skin, melatonin provides protection through each of these functions (3). Melatonin and its metabolites are major skin protectants (1).  

Figure 2: Overview of the pleiotropic effects of melatonin and its metabolites as major skin protectants.

Image credit: Bocheva G, Slominski RM, Janjetovic Z, Kim TK, Böhm M, Steinbrink K, Reiter RJ, Kleszczyński K, Slominski AT. Protective Role of Melatonin and Its Metabolites in Skin Aging. Int J Mol Sci. 2022 Jan 22;23(3):1238. doi: 10.3390/ijms23031238. PMID: 35163162; PMCID: PMC8835651.  (https://creativecommons.org/licenses/by/4.0/).

Skin and Sunlight

Exposure to sunlight is a major contributor to the circadian rhythm. Exposure to early morning sunlight, followed by the darkness of the evening, regulates a healthy circadian rhythm for optimal sleep. Despite the skin’s protective measures to counteract oxidative stress, prolonged exposure to ultraviolet radiation (UVR) from sunlight can lead to increased skin damage and premature aging of the skin known as photoaging (1,3). Clinically, this can present as wrinkles, discoloration, & dry and/or rough skin, while also decreasing the skin’s function as a barrier to external factors (3).

Exposure to UVR (3):

• Causes damage to DNA

• Creates an oxidizing environment, increasing skin cancer risk

• Causes overexpression of reactive oxygen species (ROS)

• Increases inflammation

• Increases apoptosis

• Decreases cellular and humoral immunity

Melatonin and Health Skin Aging

Melatonin’s powerful free radical scavenging properties can quickly reduce oxidative stress caused by exposure to UVA and UVB radiation (1). Additionally, melatonin can stimulate the activation of antioxidant enzymes, such as glutathione, catalase, and superoxide dismutase (1). Melatonin also shows promise for protecting the skin from environmental pollutants by upregulating SIRT1, which will downregulate collagen breakdown and decrease inflammation (1,3).

Figure 3: A possible role of melatonin in the prevention and treatment of physiological skin aging. Red crosses (X) indicate the protective action of melatonin against inflammaging, oxidative stress, and mitochondrial damage.

Image credit: Bocheva G, Slominski RM, Janjetovic Z, Kim TK, Böhm M, Steinbrink K, Reiter RJ, Kleszczyński K, Slominski AT. Protective Role of Melatonin and Its Metabolites in Skin Aging. Int J Mol Sci. 2022 Jan 22;23(3):1238. doi: 10.3390/ijms23031238. PMID: 35163162; PMCID: PMC8835651.  (https://creativecommons.org/licenses/by/4.0/).

Phytomelatonin

Phytomelatonin has been found to be superior to synthetic melatonin for its antioxidant, anti-radical, and anti-inflammatory effects. One study found a 100% improvement in cellular health, measured by reactive oxygen species in skin cells when using phytomelatonin compared to synthetic melatonin (8).