top of page

Skin Aging

Overview

Health is commonly reported as complete well-being and the absence of disease. Healthy skin has been reported as “…one of the principal factors representing overall “well-being” and the perception of “health” in humans…”(1). The general characteristics of healthy skin include even skin tone, smooth and even texture (free of bumps, acne, or other dermatological concerns), well-hydrated (free of dryness, fine lines, and wrinkles), and firm (free of sagging or loose skin).

 

The skin is a source of many hormones, including melatonin and vitamin D.  The skin plays a critical role in maintaining homeostasis by regulating oxidative stress and circadian rhythm. In response to oxidative stress, the skin produces melatonin, vitamin D, and melanin (1). Specifically, vitamin D and melatonin may work synergistically in the skin. Ultraviolet (UV)-B radiation is required to convert 7-dehydrocholesterol in the skin to vitamin D3. At the same time, melatonin is an antioxidant in the skin to ward off the damaging effects of UV light (2). Like the pineal gland, skin synthesizes melatonin rhythmically, with the highest levels of cutaneous melatonin in the evening hours (1).

 

Biological aging affects the entire human body, including the skin. The factors that influence healthy aging, also influence healthy skin, including (1,3):

 

Skin aging is influenced by environmental factors such as pollutants, lifestyle factors such as smoking, and internal factors, such as the decline of hormones that occurs with the natural aging process (1).

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

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).  

Melatonin and its metabolites

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).

melatonin MOA in skin

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). 

PM to SM.png

Figure 4: ROS fluorescence (cellular damage) in human skin cells line by phytomelatonin (blue bars) and synthetic melatonin (gray bars). Data are expressed as ROS fluorescence using 50 mcg/mL.

Data Obtained from: Kukula-Koch W, Szwajgier D, Gaweł-Bęben K, Strzępek-Gomółka M, Głowniak K, Meissner HO. Is phytomelatonin complex better than synthetic melatonin? The assessment of the antiradical and anti-inflammatory properties. Molecules. Published online 2021. doi:10.3390/molecules26196087

Melatonin Dosing for Skin

It has been demonstrated that topical application of melatonin resulted in increased melatonin levels in the blood, likely due to the lipophilic action of melatonin (9). Early studies showed photoprotective effects using topical melatonin alone (0.05 and 0.5%) (10), or in combination with vitamin E and vitamin C (11). However, at present, limited human studies have explored specific doses of melatonin for skin health. One study reported topical melatonin cream 12.5% provided protection against sun damage and erythema, whereas the 0.5 and 2.5% creams did not (12).

 

What the future holds

In the future, there may be more skincare innovations that involve both vitamin D and melatonin due to the activities they share in the skin (13). Access to the skin with oral melatonin is limited, therefore, topical melatonin may be a worthy skin anti-aging therapy due to its photoprotective activity to reduce or prevent wrinkles, sagging, and roughness (1).  

 

Written by Kim Ross, DCN

Reviewed by Deanna Minich, PhD

June 6, 2023

 

References

 

1. Bocheva G, Slominski RM, Janjetovic Z, Kim TK, Böhm M, Steinbrink K, et al. Protective Role of Melatonin and Its Metabolites in Skin Aging. Int J Mol Sci. 2022 Jan 22;23(3):1238.

2. Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Vol. 5, Dermato-Endocrinology. 2013.

3. Gao T, Li Y, Wang X, Ren F. The Melatonin–Mitochondrial Axis: Engaging the Repercussions of Ultraviolet Radiation Photoaging on the Skin’s Circadian Rhythm. Antioxidants. 2023 Apr 26;12(5):1000.

4. Tan DX, Xu B, Zhou X, Reiter RJ. Pineal calcification, melatonin production, aging, associated health consequences and rejuvenation of the pineal gland. Vol. 23, Molecules. 2018.

5. Gitto E, Tan DX, Reiter RJ, Karbownik M, Manchester LC, Cuzzocrea S, et al. Individual and synergistic antioxidative actions of melatonin: studies with vitamin E, vitamin C, glutathione and desferrrioxamine (desferoxamine) in rat liver homogenates. Journal of Pharmacy and Pharmacology. 2010;53(10).

6. Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ. One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species? Vol. 42, Journal of Pineal Research. 2007.

7. Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients [Internet]. 2022;14(19). Available from: https://www.mdpi.com/2072-6643/14/19/3934/htm

8. Kukula-Koch W, Szwajgier D, Gaweł-Bęben K, Strzępek-Gomółka M, Głowniak K, Meissner HO. Is phytomelatonin complex better than synthetic melatonin? The assessment of the antiradical and anti-inflammatory properties. Molecules. 2021;

9. Fischer TW, Greif C, Fluhr JW, Wigger-Alberti W, Elsner P. Percutaneous Penetration of Topically Applied Melatonin in a Cream and an Alcoholic Solution. Skin Pharmacol Physiol. 2004;17(4):190–4.

10. Bangha E, Elsner P, Kistler GS. Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). A dose response study. Arch Dermatol Res. 1996 Aug;288(9):522–6.

11. Dreher, Gabard, Schwindt, Maibach. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. British Journal of Dermatology. 1998 Aug;139(2):332–9.

12.  Scheuer C, Pommergaard HC, Rosenberg J, Gögenur I. Dose dependent sun protective effect of topical melatonin: A randomized, placebo-controlled, double-blind study. J Dermatol Sci. 2016 Nov;84(2):178–85.

13. Rusanova I, Martínez-Ruiz L, Florido J, Rodríguez-Santana C, Guerra-Librero A, Acuña-Castroviejo D, et al. Protective effects of melatonin on the skin: Future perspectives. Vol. 20, International Journal of Molecular Sciences. 2019.

bottom of page