Epigenetic Modulators in Anti-Aging Skincare: Unraveling Molecular Mechanisms and Advancing Patient Applications

Background: The aging of skin is a multifaceted process influenced by both internal (chronological) and external (environmental) factors, which leads to the formation of wrinkles, a decline in elasticity, and alterations in pigmentation. Epigenetics, involving heritable changes in gene expression that do not modify the DNA sequence, is crucial in governing skin homeostasis and its reaction to environmental influences. Various epigenetic modifications, including DNA methylation, histone changes, and non-coding RNAs, play a significant role in modulating gene activity that is essential to aging characteristics. This review consolidates the molecular mechanisms and practical applications of epigenetic agents in anti-aging skincare, while also addressing challenges such as variability in studies and the requirement for extensive safety data over the long term.Methods: A comprehensive literature search was performed on PubMed, Scopus, and Web of Science, focusing on peer-reviewed research articles published between 2015 and 2025. The search utilized keywords such as "epigenetics," "anti-aging skincare," "DNA methylation," "histone modification," "non-coding RNA," and "clinical trials," which were combined using Boolean operators. The inclusion criteria emphasized studies that examined epigenetic processes related to skin aging, along with both natural and synthetic modulators, and clinical outcomes, while excluding non-peer-reviewed literature and studies on non-human subjects lacking translational relevance. The data extraction concentrated on molecular mechanisms, profiles of modulators, designs of clinical trials, and outcomes reported by patients.Results: Epigenetic alterations related to aging, such as hypermethylation of the COL1A1 promoter and changes in histone acetylation, play a role in the characteristics of aging skin. Both natural substances (like resveratrol, EGCG, quercetin, and dihydromyricetin) and synthetic compounds (including retinoids, senolytic peptides such as OS-01 and GHK-Cu, NAD+ precursors, and HDAC/DNMT inhibitors) have been found to influence epigenetic modifications. Clinical trials indicate that these agents are effective in decreasing biological skin age while enhancing hydration (by 20.37% to 44%), elasticity (by 5.3% to 25.6%), and reducing wrinkle depth (by 6.2% to 55.8%), often outperforming traditional methods. Outcomes reported by patients show a high level of satisfaction (for instance, 70% satisfaction with OS-01), albeit with someConclusions: Epigenetic modulators present a groundbreaking method for anti-aging skincare by focusing on reversible molecular processes. Their combination with personalized dermatological care, microbiome management, and innovative delivery systems shows potential for extending skin vitality. Rigorous, long-term clinical trials are essential to confirm their effectiveness and safety, paving the way for a transition to precision, expert-driven anti-aging approaches.