While vitamin C’s skin benefits are well known, new research reveals it also reactivates genes tied to epidermal renewal and thickness, potentially preventing age-related skin thinning.
As we age, our skin naturally becomes thinner and more fragile due to a decline in cell production, but now researchers have found that vitamin C can help counteract this aging process.
Using a 3D human skin model, they showed that vitamin C boosts epidermal thickness by activating genes linked to cell growth through DNA demethylation. These findings, published online in the Journal of Investigative Dermatology, suggest that vitamin C may help prevent age-related skin thinning and support healthier, stronger skin in aging individuals.
The skin acts as the body’s first line of defense against external threats. However, as we age, the epidermis—the outermost layer of skin—gradually becomes thinner and loses its protective strength. 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 combat aging’s impact on skin, numerous studies have emphasized the benefits of vitamin C, a vitamin well known for its role in skin health and antioxidant properties.
The researchers in Japan have discovered that vitamin C helps thicken the skin by directly activating genes that control skin cell growth and development. Their findings suggest that vitamin C may restore skin function by reactivating genes essential for epidermal renewal.
“[Vitamin C] seems to influence the structure and function of 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 Akihito Ishigami, PhD, vice president of the division of biology and medical sciences at Tokyo Metropolitan Institute for Geriatrics and Gerontology, who led the study, in a release.
How Vitamin C Affects Skin Regeneration
To investigate how vitamin C affects skin regeneration, the team used human epidermal equivalents, which are laboratory-grown models that closely mimic real human skin. In this model, skin cells are exposed to air on the surface while being nourished from underneath by a liquid nutrient medium, replicating the way human skin receives nutrients from underlying blood vessels while remaining exposed to the external environment.
The researchers used this model and applied vitamin C at 1.0 and 0.1 mM—concentrations comparable to those typically transported from the bloodstream into the epidermis. On assessing its effect, they found that vitamin C-treated skin showed a thicker epidermal cell layer without significantly affecting the stratum corneum (the outer layer composed of dead cells) on day seven.
By day 14, the inner layer was even thicker, and the outer layer was found to be thinner, suggesting that vitamin C promotes the formation and division of keratinocytes. Samples treated with vitamin C showed increased cell proliferation, demonstrated by a higher number of Ki-67-positive cells—a protein marker present in the nucleus of actively dividing cells.
Importantly, the study revealed that vitamin C helps skin cells grow by reactivating genes associated with cell proliferation. It does so by promoting the removal of methyl groups from DNA, in a process known as DNA demethylation. When DNA is methylated, methyl groups attach to cytosine bases, which can prevent the DNA from being transcribed or read, thereby suppressing gene activity. Conversely, by promoting DNA demethylation, vitamin C promotes gene expression and helps cells to grow, multiply, and differentiate.
The study suggests that vitamin C supports active DNA demethylation by sustaining the function of TET enzymes (ten-eleven translocation enzymes), which regulate gene activity. These enzymes convert 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC), a process in which Fe2+ is oxidized to Fe3+. Vitamin C helps maintain TET enzyme activity by donating electrons to regenerate Fe2+ from Fe3+, enabling continued DNA demethylation.
Triggering Genetic Pathways for Growth and Repair
The researchers further identified over 10,138 hypomethylated differentially methylated regions in vitamin C-treated skin and observed a 1.6- to 75.2-fold increase in the expression of 12 key proliferation-related genes. When a TET enzyme inhibitor was applied, these effects were reversed, confirming that vitamin C functions through TET-mediated DNA demethylation.
These findings reveal how vitamin C promotes skin renewal by triggering genetic pathways involved in growth and repair. This suggests that vitamin C may be particularly helpful for older adults or those with damaged or thinning skin, boosting the skin’s natural capacity to regenerate and strengthen itself.
“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,” says Ishigami in a release.
