Study suggests vitamin C could help slow thinning skin with age

A vitamin found in many fresh fruits and vegetables may help slow a visible sign of ageing: skin that becomes thinner.

New research reports that nourishing lab-grown models of human skin with vitamin C increases epidermal thickness, apparently by switching back on genes involved in cell growth. Importantly, the levels of vitamin C that normally reach skin through the bloodstream were enough to produce a measurable change.

Led by pharmaceutical scientist Yasunori Sato of Hokuriku University in Japan, the work highlights vitamin C as a possible way to hold back at least some age-related changes in the body’s largest organ.

"Vitamin C seems to influence the structure and function of epidermis, especially by controlling the growth of epidermal cells," explains biologist Akihito Ishigami of the Tokyo Metropolitan Institute for Geriatrics and Gerontology.

"We investigated whether it promotes cell proliferation and differentiation via epigenetic changes."

Vitamin C, the epidermis, and thinning skin

Healthy human skin contains relatively high concentrations of vitamin C, which hints that the vitamin is actively accumulated. By contrast, levels tend to be reduced in older skin or skin damaged by UV exposure. Vitamin C is already known to support skin health by stimulating collagen production, easing UV-related damage, and offering antioxidant protection.

Researchers also know that vitamin C is involved in DNA demethylation - the removal of methyl groups - a process that contributes to genetic stability and the regulation of gene expression.

Adding or removing methyl groups functions like a molecular switch, capable of turning genes on or off without altering the underlying genomic sequence.

What remained uncertain was how demethylation affects the differentiation of keratinocytes, the skin cells that make up most of the human epidermis.

How keratinocytes build the skin’s outer layers

Keratinocytes are formed at the deepest layer of the epidermis and gradually move upwards through several layers as they mature. In time, they become the dead cells that form the outermost layer of skin, the stratum corneum.

The stratum corneum is made entirely of dead cells and acts as a protective barrier for the living cells beneath. It is also the surface layer from which dead skin cells are shed, continuously replaced by keratinocytes rising from lower layers.

Lab-grown human skin models and vitamin C exposure

To investigate vitamin C’s role, the team cultured human keratinocytes in petri dishes in a way designed to resemble real skin: the upper layer was exposed to air, while the cells were supplied with a nutrient solution from below.

The researchers supplemented the nutrient solution with vitamin C at concentrations comparable to those delivered to skin by the circulatory system. A separate set of cells was grown under the same conditions but without vitamin C, serving as the control.

After one week, the vitamin C–nourished models had a thicker layer of living epidermal cells than the control group, while the stratum corneum showed no change. After 14 days, the living epidermal layer was thicker again, and the stratum corneum had become thinner - a pattern consistent with vitamin C encouraging cell proliferation.

Demethylation, iron-dependent enzymes, and gene reactivation

The team then sequenced DNA and RNA from their samples. They linked the increased proliferation to demethylation, which they propose is supported by vitamin C maintaining the activity of enzymes that control gene activity.

These enzymes rely on a particular form of iron to carry out demethylation, and vitamin C helps to regenerate that iron form. In effect, this allows genes tied to cell proliferation to be reactivated.

With vitamin C present, expression of 12 key proliferation genes rose in the samples - in some cases by as much as 75 times.

When the researchers used an inhibitor targeting the enzyme, the changes were undone, indicating that vitamin C is acting through this pathway. The findings point to the vitamin as a potential basis for treatments aimed at countering the effects of ageing.

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

The study has been published in the Journal of Investigative Dermatology.