How Does Vitamin C Repair the Skin Barrier? It Can Rewrite Epidermal Genes

As the global population ages, skin aging issues are gradually becoming a core focus for future skincare product development.

Consequently, whether a cosmetic ingredient can impart robust barrier function to the skin has become the most critical challenge in the skincare field. How can new ingredients be developed to enhance the skin’s anti-aging capacity? Scientists have discovered that Vitamin C (VC) can not only perform its traditional functions but also promote epidermal thickening to boost the skin barrier’s capabilities.

It is well-known that typical signs of aging include epidermal thinning, decreased cell proliferation, which subsequently lead to dry skin, sensitivity, and fine lines. This suggests that if a skincare ingredient can alleviate the problem of skin thinning, it could significantly aid in skin anti-aging.

 

A latest study on VC: It Can Actually Rewrite Epidermal Genes

For a long time, Vitamin C (Ascorbic Acid, VC), a recognized traditional ingredient, has had its efficacy primarily concentrated on the two classic areas: whitening and antioxidant defense.

However, a breakthrough study from the Tokyo Metropolitan Institute of Gerontology (TMIG) in Japan has unexpectedly unveiled the mysterious mechanism of VC in the anti-aging domain. This finding, published in the authoritative journal Investigative Dermatology, reveals that VC can directly promote epidermal thickening through a specific epigenetic mechanism, thereby ameliorating the structural thinning and impaired barrier function caused by aging.

This study, published by the Tokyo Metropolitan Institute of Gerontology (TMIG) in Investigative Dermatology, provides detailed quantitative evidence.Quantitative Data on Epidermal Structure Improvement:

IndicatorExperimental Treatment GroupTime Point of ChangeKey Quantitative Finding
Epidermal Thickness1.0 mM or 0.1 mM VC (Sodium Salt)After 7 DaysA significant increase in the thickness of the epidermal cell layer was observed.
Epidermal Thickness1.0 mM or 0.1 mM VC (Sodium Salt)After 14 DaysThe epidermis further thickened, while the stratum corneum (outermost layer) slightly thinned, indicating that VC promoted cell turnover.
Cell Proliferative Activity1.0 mM or 0.1 mM VC (Sodium Salt)7 and 14 DaysThe number of Ki-67 positive cells (proliferation markers) significantly increased, suggesting enhanced proliferative activity of keratinocytes.

How does it achieve this? Citing the latest 2025 research, this article provides an in-depth analysis of the other facet of Vitamin C.

 The Revolutionary Mechanism of VC in Promoting Epidermal Proliferation: DNA Demethylation

The innovation of this TMIG study lies in its first confirmation that VC can directly achieve the “internal remodeling” of skin structure through gene regulation. Its core principle can be summarized in three steps:

1. Experimental Verification: Structural Thickening in a 3D Epidermal Model

The TMIG research team employed a 3D human epidermal equivalent model which highly simulates the structure of real human skin.

The researchers introduced VC at concentrations of 1.0 mM and 0.1 mM into the model—levels close to what can be transported to the epidermis via blood circulation. The experimental results demonstrated that VC significantly promoted epidermal thickening. Furthermore, after 7 days, the thickness of the epidermal cell layer markedly increased.

When the experiment progressed to 14 days, the inner epidermal cells thickened further, and the number of proliferation markers (Ki-67 positive cells) significantly rose, clearly indicating that VC greatly activated the active proliferation of keratinocytes.

 

2. Molecular Mechanism: TET Enzymes and the “Gene Switch” Effect

In-depth molecular mechanism studies revealed that VC activates previously “silenced” cell proliferation genes by promoting DNA demethylation.

Crucially, Vitamin C acts as a cofactor for the TET (ten-eleven translocation) family of enzymes, supporting their function. In layman’s terms, the TET enzyme acts like an “eraser” that removes methyl groups from DNA.

In the experiment, researchers identified over 10,000 demethylated regions and found a substantial increase in the expression levels of 12 key genes related to cell proliferation and DNA replication. The expression of some of these genes even increased by 1.6 to 75.2 times. When the researchers used a TET enzyme inhibitor, the VC-induced proliferative effect was significantly reversed.

 

3. Efficacy Extension: VC Shifts from “External Defense” to “Internal Remodeling”

This research extends VC’s skincare significance from the traditional scavenging of free radicals to “internal remodeling.” It can enhance the skin’s ability to resist external stimuli and retain moisture by increasing epidermal thickness.

Moreover, it can directly activate cell growth, offering deep-level restorative potential for damaged skin.

Future Implications for the Cosmetics Industry: Ushering in the “Barrier Construction” Era for VC

Traditional theories may have considered VC a relatively conventional skincare ingredient. However, this breakthrough provides revolutionary inspiration for the development of VC in skincare ingredients.

Industry insiders widely believe that VC’s status will be upgraded to a “Core Active Ingredient for Skin Barrier Construction.”

One industry expert commented: “The significance of this study lies in providing a perspective to reverse the fate of senescent cells at the gene level. VC is no longer merely an ‘antioxidant’; it is an epigenetic modulator. This means that in future anti-aging formulations, we can utilize VC to reprogram aging cells and restore their innate regenerative capacity.”

The future trend for anti-aging formulations is to increasingly utilize VC’s epigenetic effects, combined with other permeation-enhancing technologies, to ensure VC reaches the deep epidermis to exert its pro-proliferative efficacy.

The study indicates that since epigenetic modifications are reversible, VC-mediated epigenetic modifications offer new insights into clinical therapeutic strategies.

Important Limitations and Outlook

The research team also noted that despite the encouraging results, limitations still exist.

For instance, in this experiment, researchers used VC sodium salt to avoid pH-induced changes. Additionally, to rule out confounding factors, they focused solely on gene transcription rather than protein levels.

However, it is certain that with further research, combined with the analysis of other epigenetic factors like histone modifications, Vitamin C is poised to truly realize its revolutionary role of “internal remodeling” in anti-aging products.

 

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