Non-ablative fractional laser 1940nm treatment series modulates epigenetic pathways and signs of skin aging: a split face investigation

To address this, we conducted a split-face, paired longitudinal study in 22 adults treated with a 1940-nm non-ablative fractional laser (NAFL). Epidermal samples were collected by tape stripping from treated and contralateral control sites at baseline, immediately after the first treatment, and at 1, 3, and 6 months.

Enzymatic methyl-sequencing profiled ~3.8 million CpGs per sample; clinical endpoints included pigmentation, texture, and global aesthetic scores. No significant differentially methylated regions (DMRs) were detected immediately post-treatment, but 635 DMRs emerged from 1 month after the final session, expanding through 3 months and stabilizing by 6 months. These loci were enriched for pathways involved in epidermal differentiation, collagen organization, wound response, and stem-cell maintenance, and showed selective resetting at Polycomb-regulated and WNT-signaling genes.