Screened from 1,800 Natural Compounds, DHM Reactivates Skin Genes Silenced by Aging
Skin aging research has long focused on blocking collagen-degrading enzymes or shielding the skin from UV exposure. Both approaches treat aging as something to slow from the outside. A study published in Frontiers in Aging takes a different direction entirely: identifying a compound that can reactivate skin genes that aging has gradually switched off.
That compound is DHM, dihydromyricetin.
The Molecular Tags That Age Your Skin
To understand what DHM does, it helps to understand what happens to DNA over time. Aging introduces a process called DNA methylation, in which small molecules called methyl groups attach to specific points along the genome. Once these tags are in place, the genes they cover stop being read.
The genes that go quiet are not random. They include the instructions for collagen synthesis, cellular renewal, and antioxidant response, precisely the functions associated with young, resilient skin. The enzyme that places these methyl tags is called DNMT1. The more active DNMT1 becomes, the faster methylation accumulates, and the more of these essential genes fall silent.
Methylation patterns can be measured, and that measurement reveals something more meaningful than a birth year: the biological age of the skin itself.
One Compound from a Screen of 1,800
The research team ran a systematic screen of 1,800 natural compounds and 640 FDA-approved drugs, evaluating each for its ability to inhibit DNMT1. DHM was the compound that emerged.
DHM is a flavonoid, a class of plant polyphenols, extracted primarily from Ampelopsis grossedentata, a vine plant used in traditional herbal preparations. Grapes and some berry varieties contain it in smaller amounts. Its ability to inhibit DNMT1 means it can reduce the accumulation of methyl tags and restore activity to genes that had been effectively silenced by the aging process.
Clinical Results in Women Aged 50 to 65
The researchers conducted an 8-week clinical trial with 19 women between the ages of 50 and 65, applying a topical DHM formulation throughout the study period.
The results were specific. Thirty-four genes that had been methylated into silence were reactivated. Twenty-three of those genes are directly associated with wrinkle formation. The pattern of gene activity following DHM application matched what is observed in the epidermis of younger skin.
Biological skin age was evaluated using multiple methylation-based measurement approaches, including the Skin and Blood clock and the human epidermis clock. Across these measures, biological skin age decreased by an average of approximately 2 years. Wrinkle grade prediction shifted by the equivalent of 3.7 younger years.
78% Reduction in Wrinkle Volume, Measured in 3D
A separate clinical study with 43 participants used three-dimensional skin analysis equipment to quantify DHM’s effect on wrinkle depth and volume. This method maps the surface topography of the skin to calculate the actual volume of wrinkles numerically, rather than relying on visual grading alone. The outcome was a reduction in wrinkle volume of up to 78%.
Safety profiling found low potential for short-term and repeated-dose toxicity.
Two Aging Pathways, One Compound
DHM’s properties extend beyond DNMT1 inhibition. It is also being studied as an inhibitor of RAGE, the receptor for advanced glycation end-products. Glycation is a process in which sugar molecules bind to skin proteins, stiffening them and contributing to loss of elasticity. A single compound that acts on both the methylation pathway and the glycation pathway is drawing increasing attention from researchers working on skin aging biology.
The broader shift this research represents is worth noting. For years, the dominant strategies in skin science have been adding things from the outside (collagen, retinoids, growth factors) or blocking degradation (protease inhibitors, antioxidants). DHM points toward a third approach: working at the level of gene expression to restore the skin’s own capacity to behave as younger skin does. The clinical data behind it makes that possibility more than theoretical.