Endogenous Upstream Bioelectrical Modulation of Inflammatory, Angiogenic, and Anti- Senescent Pathways in Human Dermal Fibroblasts Using the REAC-ACT Protocol

Chronic low-grade inflammation and cellular senescence contribute significantly to skin aging and impaired tissue repair. Fibroblasts, key regulators of extracellular matrix remodeling and cytokine activity, are strategic targets for regenerative interventions. This study evaluates the effects of the Anti-Inflammatory Cellular Treatment (ACT) protocol, based on upstream endogenous bioelectrical modulation using Radio Electric Asymmetric Conveyer (REAC) technology, on human dermal fibroblasts (HFF-1), focusing on key molecular pathways involved in inflammation, oxidative stress, angiogenesis, and cellular senescence. HFF-1 cells underwent nine 30-minute REAC-ACT sessions. Gene expression was analyzed via RT-qPCR; protein levels of cytokines and related mediators were measured using ELISA and immunofluorescence. Statistical significance was assessed with Kruskal–Wallis, ANOVA with Tukey correction, and Wilcoxon tests. REAC-ACT significantly upregulated SIRT1 and VEGF, with modest increases in Nox4. Key cytokines (IL-1α, IL-1β, IL-2, IL-8) were selectively elevated, suggesting a reparative rather than pro-inflammatory response. FOXO1 expression increased, while mTOR was downregulated, indicating activation of antioxidant and anti-senescent signaling. REAC-ACT exerts upstream regulatory effects on inflammation, vascular remodeling, and senescence-related signaling, supporting its potential as a non-invasive therapeutic strategy in regenerative and anti-aging dermatology. These findings were consistently observed across biological replicates, supporting the reproducibility and translational relevance of this upstream bioelectrical modulation approach.