The skin is our first protective barrier. With time, the outer layer, the epidermis, thins out. It loses its ability to block external harm. Keratinocytes form most of this layer, moving upward to create the skin’s shield.
Vitamin C (VC), widely known for its antioxidant power, has also been studied many times in the past for its ability to repair skin. New research adds a deeper genetic angle to its importance.
A Japanese study, published in the Journal of Investigative Dermatology, shows how vitamin C thickens the skin by reactivating specific genes. It strengthens the skin by encouraging cell renewal through epigenetic changes.
“VC seems to influence the structure and function of epidermis, especially by controlling the growth of epidermal cells,” explains Dr. Akihito Ishigami, Vice President at Tokyo Metropolitan Institute for Geriatrics and Gerontology (TMGHIG), who led the research.
“In this study, we investigated whether it promotes cell proliferation and differentiation via epigenetic changes.”
Also known as ascorbic acid, vitamin C plays a critical role in human biology as a powerful antioxidant and essential cofactor in various enzymatic reactions.
The body uses it to synthesize collagen, a key structural protein found in skin, blood vessels, and connective tissues.
It also assists in the production of neurotransmitters such as norepinephrine and aids in metabolizing certain amino acids.
Unlike most animals, humans cannot synthesize vitamin C internally and must obtain it through diet – primarily from fruits and vegetables like oranges, kiwis, strawberries, bell peppers, and broccoli.
Beyond its structural and metabolic roles, vitamin C strengthens the immune system by supporting the function of white blood cells and enhancing skin’s barrier defenses.
Its antioxidant properties help neutralize free radicals, potentially lowering the risk of chronic diseases like cardiovascular disease and cancer.
Researchers wanted to see how vitamin C affects skin growth. But instead of testing on real human skin, they created lab-grown skin called human epidermal equivalents. These are 3D skin models that behave like real skin.
In these models, the top layer is exposed to air, like human skin facing the environment, while the bottom layer gets nutrients, just like how blood vessels nourish real skin from underneath.
They applied vitamin C in two doses: 0.1 and 1.0 millimolar. After 7 days, they noticed that the living part of the skin became thicker, meaning more skin cells had grown.
The outermost dead skin layer didn’t change at this point. But by day 14, the living layer had thickened even more, and the outer dead layer had become thinner.
This suggested that vitamin C was making the skin produce more keratinocytes, which are the main cells that build the protective barrier.
Samples treated with vitamin C had more Ki-67-positive cells, markers of active division and showed faster skin regeneration. The study then looked into how vitamin C enabled this increase.
They discovered that vitamin C reactivates key genes by removing methyl groups from DNA. These methyl groups silence genes. Their removal allows the genes to turn on, promoting skin cell growth and repair.
TET enzymes carry out DNA demethylation. They transform 5-methylcytosine into 5-hydroxymethylcytosine.
This step requires iron in its Fe2+ form. When iron becomes Fe3+, the process stops. Vitamin C donates electrons to turn Fe3+ back into Fe2+, keeping the process active.
The study identified more than 10,000 areas of DNA that became hypomethylated with vitamin C. Expression of 12 key genes rose between 1.6 to 75.2 times.
When TET enzymes were blocked, the effects reversed. This confirmed the role of TET-mediated demethylation in skin thickening.
The paper supports these results with additional experiments. It describes how vitamin C promotes transcriptional activation by increasing chromatin accessibility.
Vitamin C-treated skin showed elevated chromatin openness around growth-promoting genes.
The study shows enrichment of open chromatin regions near gene bodies related to cell proliferation. These genes are essential in epidermal development.
It further proves vitamin C’s action by displaying upregulation of genes such as DLX5, CXCL14, and EFNA1. These genes promote keratinocyte growth and skin structure organization.
Moreover, the paper presents long-read sequencing data. This technique confirmed that vitamin C increases the expression of full-length, functional gene transcripts.
This strengthens the idea that vitamin C not only activates genes but does so in a way that results in usable proteins.
These findings suggest vitamin C can strengthen thin or aging skin. It works by restarting growth pathways that decline with age. It reactivates genes and supports cellular rebuilding at a molecular level.
“We found that VC helps thicken the skin by encouraging keratinocyte proliferation through DNA demethylation, making it a promising treatment for thinning skin, especially in older adults,” concludes Dr. Ishigami.
As a result of this study, and all of the research that preceded it, vitamin C may soon play a bigger role in daily skincare routines, not just as an antioxidant, but as a genetic rejuvenator.
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Dr. Ishigami worked with Hokuriku University and ROHTO Pharmaceutical Co., Ltd. Key contributors included Professors Ayami Sato, Yasunori Sato, and Toshiyuki Kimura.
The study is published in the Journal of Investigative Dermatology.
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