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

ABSTRACT: Skin aging is driven by cumulative environmental damage and epigenetic dysregulation, yet it is unclear whether energy-based rejuvenation therapies can durably remodel the cutaneous methylome. 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. NAFL reversed age-associated methylation change at >83% of age-linked CpGs and engaged gene sets previously implicated in molecular rejuvenation. Treatment also induced transient, treatment-specific DMRs related to immune and stress responses. Epigenetic remodeling paralleled significant clinical improvements, indicating that 1940-nm NAFL drives durable molecular rejuvenation rather than transient repair.

ORGANISM(S): Homo sapiens

PROVIDER: GSE315794 | GEO | 2026/07/08

REPOSITORIES: GEO

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Project description:Background: Psoriasis is a T cell-mediated chronic autoimmune/inflammatory disease. While some patients experience disease limited to the skin (skin psoriasis), others develop joint involvement (psoriatic arthritis; PsA). In the absence of disease- and/or outcome-specific biomarkers, and as arthritis can precede skin manifestations, diagnostic and therapeutic delays are common and contribute to disease burden and damage accrual. Objective: Altered epigenetic marks, including DNA methylation, contribute to effector T cell phenotypes and altered cytokine expression in autoimmune/inflammatory diseases. This project aimed at the identification of disease-/outcome-specific DNA methylation signatures in CD8+ T cells from patients with psoriasis and PsA as compared to heathy controls. Method: Peripheral blood CD8+ T cells from 9 healthy controls, 10 psoriasis and 7 PsA patients were collected to analyze DNA methylation marks using Illumina Human Methylation EPIC BeadChips (>850,000 CpGs per sample). Bioinformatic analysis was performed using R (minfi, limma, ChAMP and DMRcate packages). Results: DNA methylation profiles in CD8+ T cells differentiate healthy controls from psoriasis patients (397 Differentially Methylated Positions (DMPs); 9 Differentially Methylated Regions (DMRs) when ≥CpGs per DMR were considered; 2 DMRs for ≥10 CpGs). Furthermore, patients with skin psoriasis can be discriminated from PsA patients (1861 DMPs, 20 DMRs (≥5 CpGs per region), 4 DMRs (≥10 CpGs per region)). Gene ontology (GO) analyses considering genes with ≥1 DMP in their promoter delivered methylation defects in skin psoriasis and PsA primarily affecting the BMP signaling pathway and endopeptidase regulator activity, respectively. GO analysis of genes associated with DMRs between skin psoriasis and PsA demonstrated an enrichment of GABAergic neuron and cortex neuron development pathways. Treatment with cytokine blockers associated with DNA methylation changes (2372 DMPs; 1907 DMPs within promoters, 7 DMRs (≥5CpG per regions)) affecting transforming growth factor beta receptor and transmembrane receptor protein serine/threonine kinase signaling pathways. Lastly, a methylation score including TNF and IL-17 pathway associated DMPs inverse correlates with skin disease activity scores (PASI). Conclusion: Patients with skin psoriasis exhibit DNA methylation patterns in CD8+ T cells that allow differentiation from PsA patients and healthy individuals, and reflect clinical activity of skin disease. Thus, DNA methylation profiling promises potential as diagnostic and prognostic tool to be used for molecular patient stratification towards individualized treatment. This project aimed at the identification of disease-/outcome-specific DNA methylation signatures in CD8+ T cells from patients with psoriasis and PsA as compared to heathy controls.

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

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