A RECENT study using a three-dimensional human epidermal equivalent model has revealed that vitamin C (L-ascorbic acid) significantly promotes skin cell proliferation and thickening through epigenetic modifications. These findings enhance our understanding of how vitamin C maintains skin health and offers promising insights into anti-ageing therapies.
The epidermis is a dynamic tissue composed mainly of keratinocytes, which undergo a tightly regulated process of proliferation and differentiation across distinct layers. Disruptions in this process, particularly with age, lead to compromised skin function and appearance. Previous research has shown that vitamin C improves collagen synthesis, reduces UV-induced skin damage, and supports pigmentation balance. However, its precise mechanisms in epidermal cell regulation remained unclear.
In this study, researchers demonstrated that vitamin C increases the thickness of the epidermis and boosts keratinocyte proliferation without necessarily enhancing differentiation. DNA microarray and whole-genome bisulfite sequencing (WGBS) revealed that vitamin C treatment led to the hypomethylation of over 10,000 genomic regions and the upregulation of genes related to cell proliferation. This effect was mediated through the activation of TET enzymes, which convert 5-methylcytosine to 5-hydroxymethylcytosine, a crucial step in DNA demethylation.
Notably, the expression of several key proliferation-associated genes, including ROS1, SOX9, and HDAC1, was significantly increased following vitamin C treatment. The effect was reversed when TET activity was inhibited, confirming vitamin C’s role in driving gene expression through epigenetic means.
While vitamin C has been known to promote differentiation in other cell types, this study suggests that in keratinocytes, it primarily enhances proliferation through epigenetic reprogramming. This divergence highlights the tissue-specific nature of vitamin C’s effects.
Though the study faced limitations, such as not measuring protein levels of identified genes, it provides compelling evidence for vitamin C’s role in skin renewal. These findings pave the way for further exploration into vitamin C-based epigenetic therapies aimed at combating skin ageing and maintaining epidermal integrity.
Reference
Sato Y et al. Vitamin C promotes epidermal proliferation by promoting DNA demethylation of proliferation-related genes in human epidermal equivalents. J Invest Dermatol. 2025;DOI:10.1016/j.jid.2025.03.040.
