Epigenetic Skin Aging and Its Reversal to Improve Skin Longevity across Ethnicities and Phototypes Using a Dihydromyricetin-Containing Serum: Results from a Prospective, Single-Cohort Study

Introduction: Skin aging is driven by intrinsic and extrinsic factors. Epigenetic alterations are one primary hallmark of aging and powerful biomarkers of biological skin age. To investigate epigenetic skin aging mechanisms and their regulation as a skin longevity approach across diverse ethnicities and phototypes, we assessed epidermal methylomes from white, African, and Asian donors. Methods: We collected epidermis samples from 17 multi-ethnic donors with diverse phototypes using a newly established tape-stripping method followed by array-based DNA methylation profiling to investigate the robustness of DNA methylation clocks across diverse ethnic backgrounds. Additionally, we conducted a clinical study with 60 participants representing Fitzpatrick phototypes I–VI. Diverse clinical parameters and biological skin age of the volunteers were determined at baseline and after applying a serum containing the natural epigenetic inhibitor dihydromyricetin (DHM) for 8 weeks to investigate skin longevity effects across phototypes. Results: Data analysis revealed that age-dependent DNA hypermethylation is conserved across populations and affects genes essential for keratinocyte vitality and longevity. A newly developed epidermal methylation clock accurately predicted biological age in multi-ethnic cohorts, confirming the robustness of epigenetic age estimation across phototypes. Topical application of a DHM-containing serum significantly reduced epidermal DNA methylation age. Epigenetic rejuvenation was associated with clinical improvements, including reduced skin roughness and wrinkle visibility and occupancy, and increased dermal echogenicity. Conclusions: Together, these findings establish that epigenetic aging signatures are conserved across ethnicities and that targeted modulation using a DHM-containing topical formulation can reverse biological skin age while improving structural and visible signs of aging. This work provides the clinical evidence supporting epigenetic rejuvenation as a viable strategy for skin longevity across diverse populations.