Evaluation of the anti-ageing potential of manganese ion in human dermal fibroblasts.

During skin ageing, fibroblasts' proliferation declines, leading to reduced collagen turnover, increased in expression of senescence markers, and secretion of pro-inflammatory molecules associated with the Senescence-Associated Secretory Phenotype (SASP). The SASP generates a chronic pro-inflammatory state that causes tissue damage and impairs repair mechanisms. Among the molecular pathways implicated in ageing, the PI3K/AKT/mTOR signalling axis is now recognised as a central regulator of cellular metabolism, growth, and survival, and its attenuation has been identified as one of the main anti-ageing interventions. In this context, the present study aimed to evaluate the anti-ageing potential of the manganese ion (Mn2 +) in cultures of adult human dermal fibroblasts (HDFs). HDFs were treated with 25 µmol/L Mn2+ for 24-48 h. Cell proliferation was measured by tritiated thymidine incorporation; cell cycle progression by flow cytometry; senescence by SA-β-Gal staining; PI3K/AKT pathway activity by Western blot; and ECM-related gene expression (COL1A1, MMP1) by RT-qPCR. Mn2+ treatment enhanced proliferation and reduced the percentage of adult HDFs in the G0/G1 phase and SA-β-Gal positivity in most HDFs populations. Additionally, Mn2+ treatment reduced the expression and activation of PI3K/AKT signalling, while inducing variable effects on ECM-related gene expression, with a trend towards increased COL1A1 expression and decreased MMP1 expression in some HDF populations. This study provides evidence that Mn2+ may function as a bioactive ion influencing key ageing-related pathways, with effects extending beyond its antioxidant properties. By promoting proliferation and attenuating senescence markers, Mn²⁺ may contribute to cellular responses associated with improved dermal function. Its effects on ECM-related gene expression suggest a potential role in strategies aimed at preserving skin homeostasis and counteracting age-related dysfunction.