Preventing Skin Aging: Epigenetics-Targeted Antioxidants in Skincare

Oxidative Stress and Antioxidant Interaction in Skin Aging

Oxidative stress damage to the skin, a fundamental factor in aging, can occur as early as birth and continue throughout life. Skin oxidative damage results from an imbalance between reactive oxygen species (ROS) generation and antioxidant defenses. The unfavorable consequences include accelerated aging, increased skin diseases, loss of collagen and elastin, DNA damage, higher skin sensitivity, and enhanced pigmentation.

Visible symptoms may include wrinkling, sagging, fine lines, loss of firmness, reduced elasticity and glow, and dehydration.

ROS include hydrogen peroxide (H₂O₂), the superoxide anion radical (O₂⁻), the hydroxyl radical (·OH), hypochlorous acid (HClO), the nitric oxide radical (NO⁻), and the lipid peroxyl radical (LOO⁻). Skin ROS are mainly produced through normal metabolic reactions, cosmetic products, and continuous exposure to oxidative environments such as ultraviolet (UV) radiation from sunlight.

The Skin’s Antioxidant System

The reduction or elimination of intracellular ROS depends on the body’s antioxidant system, which consists of enzymatic and non-enzymatic antioxidants.

Enzymatic antioxidants include superoxide dismutase (SOD), catalase, and glutathione peroxidase. These enzymes convert oxidized metabolic products into hydrogen peroxide and then to water through a multistep process.

Non-enzymatic antioxidants include:
a) Small exogenous (natural) molecules such as vitamins E, C, and A, flavonoids, and carotenoids.
b) Endogenous (physiological) molecules such as uric acid, melatonin, bilirubin, and polyamines.

Non-enzymatic antioxidants function by donating electrons to scavenge and neutralize ROS.

Epigenetic Regulation and Control of Skin Aging

Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve alterations in the DNA sequence—a change in phenotype without a change in genotype—which in turn affects how cells read genes [1].

The epigenetic regulatory system primarily consists of DNA methylation, histone modification, and chromatin remodeling.

• DNA methylation is usually associated with gene repression through DNA methyltransferases and can be reversed by DNA demethylases to reactivate gene expression.
• Histone modification includes histone methylation and acetylation. Methylation may cause gene repression or activation depending on which histone site is modified, while acetylation generally promotes gene activation.
• Chromatin remodeling refers to the dynamic alteration of chromatin architecture, allowing transcription factors and other DNA-binding proteins to access DNA and regulate gene expression.

Skin aging is characterized by the accumulation of damaged macromolecules, impaired tissue renewal, and progressive loss of physiological integrity [2]. It can be classified into two main types:

1. Chronological aging, which occurs naturally over time and is primarily influenced by genetic and metabolic factors.
2. Photoaging, which results from environmental insults such as chronic sun exposure.

Both chronological aging and photoaging generate ROS, which accelerates the aging process. Therefore, reducing or eliminating ROS through the skin’s antioxidant system can slow the progression of skin aging.

The epigenetically regulated expression of anti-oxidative stress genes produces antioxidant proteins and enzymes that scavenge ROS from chemical, physical, and metabolic sources. For example, methylation of these genes results in gene inactivation, preventing antioxidant enzyme production. Conversely, demethylation reactivates the genes, allowing normal antioxidant function.

Antioxidant Mechanisms of Epigenetics-Targeted Skincare Antioxidants

Numerous studies show that epigenetics-targeted antioxidants are highly effective in protecting skin cells and tissues against oxidative stress damage. As a result, they significantly prevent or slow the progression of skin aging.

It is important to emphasize that skin condition is dynamic, influenced by environmental interactions and reversibly regulated by epigenetic mechanisms at both the gene and protein levels. Therefore, the overall antioxidant status of the skin depends on the activity of both enzymatic and non-enzymatic antioxidants.

In practical skincare, using a simple antioxidant test can help determine an individual’s skin antioxidant level and identify the most suitable skincare products.

It is equally important to verify whether antioxidant skincare products are truly effective. Even if products claim to contain antioxidant ingredients, their actual performance depends on ingredient concentration, potency, and the synergistic combination of multiple active components.

Before applying a product, evaluating whether it effectively combats oxidative stress ensures the selection of antioxidant skincare formulations that are genuinely functional and beneficial for the user.

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