Effects of a fractional non-ablative 1940nm laser targeting the epigenetic MitraClockTM and clinical end-points: A longitudinal study

Summary: Background:<b> </b>Skin aging results from intrinsic and extrinsic factors, altering DNA methylation and accelerating visible aging. Advances in epigenetic clocks now enable precise measurement of biological skin age, offering a quantitative tool to evaluate skin rejuvenation. This study investigates the impact of fractional non-ablative 1940 nm laser (Frax1940nm) on epigenetic aging and molecular pathways involved in skin homeostasis. Methods:<b> </b>A split-face pilot study (n=22, age 25-60, skin types II-III) involved three laser treatments 28 days apart. Non-invasive skin samples were collected at baseline, post-treatment 1, and 1/3/6-month follow-ups (MFU) from treated and untreated areas. DNA methylation profiling via enzymatic conversion and targeted Illumina sequencing was analyzed using MitraClock for age prediction. DMR analysis identified pathway-specific changes, and covariate analysis assessed menopause, age, and smoking effects. Paired t-tests and linear regression models adjusted for age and baseline methylation. Results:<b> </b>Epigenetic age decreased in treated skin at 6MFU (Δ -2.3 years, p≤0.05), with no significant change in untreated skin (Δ -0.4 years, p=0.21). Post-menopausal women exhibited greater short-term rejuvenation at 1MFU (Δ -1.9 years, p≤0.05). DMR analysis showed enrichment in FGFR3 and Notch signaling (adj p=0.007, p=0.02), suggesting epidermal differentiation and barrier restoration. Pigment severity reduction correlated with greater epigenetic age reversal (r=-0.72, p≤0.05), linking pigmentation improvement to molecular skin aging reversal. Conclusion: Frax1940nm reduces epigenetic skin age, with greater effects in post-menopausal women. Laser therapy modulates FGFR3 and Notch pathways, promoting skin differentiation, barrier repair, and rejuvenation. Non-invasive epigenetics offers a measurable tool for dermatological and aesthetic applications. Cristiana Banila^{2, 1}, Victoria Dyster^{2, 1}, Angel Menendez Vazquez^{2, 1}, Miruna Vasile^{2, 1}, Dimitris Katsanos^{2, 1}, Andrew Graham², Shakiba Kaveh^{2, 1} 1. Translation and Innovation Hub, Imperial College London, London, England, United Kingdom. 2. Mitra Bio Limited, London, UK, United Kingdom. Clinical Research: Interventional Research