Life Extension Magazine®

Woman feeling skin after applying topical melatonin

Topical Melatonin Promotes Youthful Skin

The age-related decline in melatonin is a factor in skin-aging. Human research shows that topically applied melatonin initiates nightly skin repair and renewal.

Scientifically reviewed by: Dr. April Parks, MD, MS, in August 2023. Written by: Robert Goldfaden and Gary Goldfaden, MD.

The impact of a good night’s sleep on maintaining younger-looking skin is often overlooked.

A recent study found that sleep quality strongly affects skin function and aging, concluding that:

“Chronic poor sleep quality is associated with increased signs of intrinsic aging, diminished skin barrier function, and lower satisfaction with appearance.”1

The skin-rejuvenating effects of sleep are partially attributed to the hormone melatonin, which exerts a wide range of anti-aging benefits.2-6

As melatonin output decreases with age,7 many people become more vulnerable to sleep disturbances that fail to adequately repair aging and photodamaged skin.

Research has revealed that topical melatonin, along with additional compounds, restores youthful reparative processes during the night to produce visible and long-lasting improvements in the health and appearance of skin.

What you need to know

  • The skin rejuvenation effects of a good night’s sleep are mediated by the broad and extensive antioxidant properties of the hormone melatonin.
  • Melatonin secretion declines with age, increasing the likelihood of sleep debt that impairs the skin’s ability to bounce back from external assaults, especially ultraviolet radiation.
  • Topical melatonin has been shown to penetrate the stratum corneum and accumulate, to initiate nightly repair and renewal.
  • Other topical agents including ectoin, acetyl-tetrapeptide-22, and coconut amino-acid complex, work through different modes of action to protect and repair damaged skin.
  • The result is healthier, younger-looking skin and a marked reduction in wrinkles, fine lines, and uneven pigmentation.

Melatoninergic Antioxidative System: Your Skin’s Internal Ultraviolet Defense


Derived from the amino acid tryptophan, melatonin is a hormone produced mainly by the brain’s pineal gland, where it regulates our internal biological clock.8

Melatonin secretion is triggered in response to darkness, and diminished in the presence of light. Over the past decade, accumulating evidence indicates that melatonin offers health-promoting benefits that extend beyond regulating circadian rhythms. For example, it provides significant protection against UV-induced skin aging (photoaging).9

When melatonin attaches to receptors on various skin cells,10,11 it suppresses oxidative stress from sun exposure.4 Melatonin is known to:

  • Act as a free-radical scavenger.12 After interacting with free radicals, melatonin is degraded to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK)—both of which possess antioxidant and anti-inflammatory effects themselves.13,14 This antioxidant cascade is known as melatoninergic antioxidative system of the skin.15
  • Activate intracellular antioxidant systems including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT).16-19

Melatonin’s versatility as a free-radical scavenger attenuates lipid peroxidation, protein oxidation, and DNA damage to promote the survival of healthy skin cells.2,4

Dermal fibroblasts are cells that manufacture collagen and elastin, which are structural proteins that keep skin young, strong, and resilient. When dermal fibroblasts were treated with melatonin before sun exposure, they showed a survival rate of 92.5% compared to just 56% in those untreated.20

By protecting against damage caused by photoaging, melatonin combats a prime culprit behind wrinkles, fine lines, loss of tone, and skin cancer, and is therefore an important ally for retaining a youthful appearance.

Why We Need Topical Melatonin


Melatonin secretion gradually declines over time, increasing our susceptibility to sleep debt that diminishes the skin’s capacity to recover from external insults.21,22

Oral ingestion of melatonin does not always provide optimal skin protection.23 A more effective method is to apply melatonin topically, where it penetrates the stratum corneum and accumulates to initiate nightly repair and renewal.24,25

A review of human studies found that topically applied melatonin safeguards against sun-induced erythema by reducing cell death, DNA damage, and oxidative stress.26

Let’s now take a look at how three other topical agents provide photoprotection, while repairing and regenerating damaged skin.

Ectoin: Natural Skin-Cell Protection

Ectoin is a natural substance found in halophilic bacteria that allows them to withstand harsh environmental stressors such as cold temperatures, sweltering UV rays, and droughts.27,28 Researchers have discovered that ectoin behaves like a sponge to bind and trap water molecules around skin structures, forming large hydration shells that protect against premature cell damage from extrinsic factors.29

In a controlled study, human volunteers with crow’s feet topically applied ectoin or a placebo twice daily for four weeks. Compared to the subjects on placebo, participants in the ectoin-treatment group experienced a mean reduction in wrinkle depth of 32%, deepest wrinkle by 17%, and wrinkle volume by 40%.30

In a double-blind, placebo-controlled trial, topical application of ectoin twice daily for four weeks in 24 women aged 30-60 significantly increased skin elasticity by 82.4% over a placebo.29

Ectoin enhances the skin’s ability to retain moisture, making it visibly softer and smoother. In another double-blind, placebo-controlled trial, a topical cream with ectoin increased skin hydration by up to 200% compared to a placebo after 12 days.29 This increased hydration level of the skin was preserved for the next seven days without treatment, thereby demonstrating the sustained moisturizing effect of Ectoin.

Acetyl Tetrapeptide-22 Stimulates Stress-Responsive Heat-Shock Proteins

The skin relies on heat-shock proteins, which act as a clean-up crew for the cellular damage induced by stressful stimuli.31,32 When inside the cell, heat-shock proteins assist in the recovery of damaged proteins, while degrading others to halt protein aggregates that impair normal cellular processes.33,34

The age-related decline in heat-shock proteins—notably heat-shock protein 70 (HSP70)—diminishes the skin’s natural stress response and accelerates aging.

A novel peptide called acetyl tetrapeptide-22 has been developed to boost HSP70 levels in the skin with or without prior stress, in turn maintaining protein homeostasis and increasing cell viability to slow down aging.35

Coconut Amino-Acid Complex Soothes Sensitive Skin


The combination of coconut amino acids and minerals (potassium and magnesium) has been shown to improve the skin’s moisture barrier and modulate the UV-induced inflammatory response in epidermal keratinocytes and dermal fibroblasts.36 This anti-inflammatory action helps soothe sensitive and irritated skin.

One research team found that coconut amino acid complex reduced the sensation of discomfort from lactic acid in humans with hypersensitive skin. They observed that coconut amino-acid complex decreased the stinging intensity of lactic acid by 46% immediately after topical application, and by 90% after one minute.36


Our skin is under attack from external forces like ultraviolet radiation that create damaging free radicals and oxidative stress, leaving behind a path of wrinkles, age spots, and mutations.

Research shows that topical compounds—including melatonin, ectoin, acetyl tetrapeptide-22, and coconut amino-acid complex—work through distinct and complementary mechanisms to offset the harmful effects of sunlight and enhance nightly repair of damaged skin to enable a younger-looking appearance.

Gary Goldfaden, MD, is a clinical dermatologist and lifetime member of the American Academy of Dermatology. He is the founder of Academy Dermatology in Hollywood, FL, and Cosmesis Skin Care. Dr. Goldfaden is a member of Life Extension®’s Medical Advisory Board. All Cosmesis products are available online.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


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