Scientists illuminate vitamin C’s role in cellular skin regeneration

New research illuminates the skin-regenerating properties of vitamin C, finding that it promotes epidermal thickening. Based on a 3D human skin model, the study demonstrates that vitamin C activates genes linked to cell growth through DNA demethylation mechanisms. 

Due to a decline in cell production, the skin naturally becomes thinner and more fragile with age, losing its protective properties. The researchers suggest vitamin C may help prevent age-related skin thinning and support healthier, firmer skin in aging individuals.

“Vitamin C seems to influence the structure and function of the epidermis, especially by controlling the growth of epidermal cells. In this study, we investigated whether it promotes cell proliferation and differentiation via epigenetic changes,” says study lead Dr. Akihito Ishigami, VP of the division of Biology and Medical Sciences at Tokyo Metropolitan Institute for Geriatrics and Gerontology, Japan.

Skin’s protective barrier

The skin acts as the body’s first line of defense against external threats. About 90% of the cells in this layer are keratinocytes, which originate from deeper layers of the epidermis and migrate upward, ultimately forming the skin’s protective barrier.

To investigate how vitamin C affects skin regeneration, the team used human epidermal equivalents, which are lab-grown models that closely mimic real human skin.

The researchers applied vitamin C to these skin models at concentrations similar to those found in the bloodstream. They observed that after seven days, the vitamin C-treated skin developed a thicker inner epidermal layer without significantly affecting the outer layer of dead cells (stratum corneum).

After seven days, the vitamin C-treated skin developed a thicker inner epidermal layer.By day 14, the inner layer was even thicker, and the outer layer had become thinner. This suggests that vitamin C helps keratinocytes form and divide. Samples treated with vitamin C showed more cell growth, indicated by an increase in a protein marker called Ki-67, which is found in actively dividing cells.

Crucially, the study found that vitamin C aids skin cell growth by reactivating genes involved in cell proliferation. It also promotes DNA demethylation, a process in which methyl groups are removed from DNA.

When methyl groups are attached to DNA, they can block genes from being read, suppressing their activity. By removing these methyl groups, vitamin C promotes gene expression, helping cells grow, multiply, and differentiate.

Role of TET enzymes

The study suggests that vitamin C supports DNA demethylation by maintaining the function of TET enzymes. These enzymes regulate gene activity by converting 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC).

This process requires iron (Fe2+), which is oxidized to Fe3+. Vitamin C helps keep TET enzymes active by donating electrons to regenerate Fe2+ from Fe3+, allowing DNA demethylation to continue.

Researchers identified over 10,000 areas in vitamin C-treated skin where DNA was less methylated. They also saw a significant increase (1.6 to 75.2 times) in the expression of 12 key genes related to cell growth. When a TET enzyme inhibitor was used, these effects were reversed, confirming that vitamin C works through TET-mediated DNA demethylation.

“We found that vitamin C helps thicken the skin by encouraging keratinocyte proliferation through DNA demethylation, making it a promising treatment for thinning skin, especially in older adults,” Dr. Ishigami concludes.