Treatment with a 1940-nm nonablative fractional laser (NAFL) may modulate DNA methylation tied to skin aging as well as skin cancer biology, new research suggested. 

In a split-face pilot study, 22 adults received three treatments with a 1940-nm NAFL. One month after treatment, 635 differentially methylated regions emerged, which expanded and then stabilized by the 6-month follow-up.

“These loci were enriched for pathways related to epidermal differentiation, collagen organization, wound response, and stem cell maintenance,” the investigators wrote.

Additionally, age-related methylation trajectories were reversed at nearly 84% of assessed sites associated with skin aging. The treatment protocol was also associated with modulated epigenetic activity for genes involved in the development of skin cancers.

Lead author Konika Patel Schallen, MD, medical director and senior vice president of global clinical operations at Candela Medical, Marlborough, Massachusetts, told Medscape Medical News that this was the first in-human split-face study to assess “this level of information and data with regard to the epigenome on the skin.” Candela is the manufacturer of the laser (Nordlys) used in the study. The other authors are from the Candela Institute for Excellence, which funded the study, and Mitra Bio, London, England.

Asked to comment, Roy G. Geronemus, MD, clinical professor of dermatology at New York University, New York City, told Medscape Medical News that in clinical practice, he’s witnessed reversals in signs of skin aging after treatments with various NAFLs.

“This is a significant, transformative study that proves what we’ve been seeing for years. It’s nice to have scientific backup for something that is well known in the dermatologic community,” said Geronemus, who was not involved with the research. 

The findings were published online on June 30 in Scientific Reports.

Progressive Rejuvenation

The study included 22 adults (age range, 20-64 years; Fitzpatrick Skin Types II-IV) who received three topical NAFL treatments on either the left or right side of the face. Each treatment was delivered 28 days apart. Laser energy ranged from 12.2 to 20 mJ (average energy delivered per treatment, 0.43 kJ), with an average pulse duration of 5.39 ms. 

At baseline, after the first treatment, and after 1-, 3-, and 6-month post-treatment, noninvasive tape stripping was used to collect epidermal samples from both treated and contralateral untreated sites (within-individual controls). This allowed for “treatment-specific methylation dynamics to be isolated from interindividual variability and environmental impacts” during the study period, the researchers wrote.

Enzymatic methyl-sequencing was used to profile more than 3.8 million CpGs (Cytosine-phosphate-Guanines) per sample. Clinical outcomes included VISIA measurements (the VISIA imaging system was used to obtain standardized facial images) and global aesthetic scores.

Results showed a “progressive and coordinated” epigenetic rejuvenating response over 6 months after the NAFL protocol, the study authors reported.

Although there were similar methylation levels right after treatment, treated areas of skin began showing significant changes vs untreated areas at the 1-month follow-up, especially in epidermal differentiation, collagen fibril organization, and wound response (false discovery rate, < 0.05 for all). The changes increased through 3 months post-treatment and then stabilized at the 6-month mark.

Further, posttreatment DNA methylation changes were “anticorrelated” with skin aging, and 83.9% of more than 168,000 CpGs showed strong differential signals in both NAFL-treated and aging reference areas.

Methylation Changes Beyond Wound Repair

There was also a significant 3.5 fold enrichment for age-hypermethylated CpGs reversed by NAFL and a 1.6 fold enrichment for age-hypomethylated CpGs hypermethylated by NAFL, suggesting a reversal of aging-linked methylation patterns. This anticorrelated shift began at 1 month post-treatment (P < .05) and continued through 6 months.

“Together, these suggest that NAFL may reshape the methylation state by both demethylating age-hyper sites and remethylating eroded regions recapitulating rejuvenation patterns,” the investigators wrote.

Changes were also observed in methylation at keratinocyte-regulating loci, including HOXB4, UBE2I, FGFR3, and PPP1R18/PPP1R26. These genes are linked to the development of basal and squamous skin cancers.

The 1940-nm wavelength “is the wavelength that most absorbs water without completely abating the skin, and we knew it made skin look good. But what we also found was that it affected the keratinocytes and the remodeling of the basal layer of the epidermis,” Schallen said.

Additionally, clinical improvements in pigmentation, texture, and overall appearance were observed in the treated skin areas, including a 38% decrease in brown spots at the 1-month evaluation.

The data, which includes integrating “molecular findings with clinical outcomes in pigmentation and global appearance,” the investigators wrote, “provide the first evidence that 1940-nm fractional laser therapy elicits remodeling of the methylome in human skin, offering insight into potential rejuvenating effects.”

‘Proof on a Cellular Level’

Geronemus noted that he participated “in some of the initial work” assessing NAFLs and was one of the authors of a 2013 paper showing their effectiveness for treating actinic keratoses. He added that treatments with these lasers have become popular for photodamage.

“What we’ve seen clinically is an overall reversal of any of the signs of aging, such as sun damage, skin quality, and skin tone — all with NAFL treatments,” Geronemus told Medscape Medical News.

The current study showing a reversal in DNA methylation and other markers “is proving what we’ve been saying since these lasers came into play,” he said. “The translation of the scientific information and the clinical outcome is the same, and it’s nice to have scientific proof of what we see on a day-to-day basis in our clinical practice.”

Although the study included only 22 participants, that was a sufficient number to confirm “what we’ve all known,” Geronemus said, adding that “it’s just proof on a cellular level.”

Early, preliminary findings from the study were presented previously at the American Society for Laser Medicine and Surgery 2025 Annual Meeting.

The study was funded by the Candela Institute for Excellence. Candela is the manufacturer of the laser used in the study. The other authors are from the Candela Institute for Excellence. Disclosure information for study authors is available in the original study publication. Geronemus reported having performed clinical trials for Candela and other laser/device companies and having no other disclosures.