Psilocybin alleviates high-glucose and high-lipid-induced skin aging in BJ5Ta fibroblasts

A high-glucose and high-lipid diet accelerates cellular aging through oxidative stress, mitochondrial dysfunction, and inflammation, contributing to collagen degradation and skin aging. Psilocybin, a naturally occurring compound, was tested on BJ-5ta fibroblasts exposed to such conditions. Post-treatment with 15 µmol/L psilocybin and co-treatment with 10 µmol/L preserved cell viability and reduced senescence markers. The 10 µmol/L co-treatment most effectively lowered apoptosis and alleviated cell cycle arrest in S phase. Psilocybin also decreased inflammatory cytokines IL-1β, IL-6, and COX-2, and co-treatment significantly upregulated elastin gene expression, though fibroblast migration increased nonsignificantly. Psilocybin shows promise as a natural compound for reducing skin aging under oxidative stress.

Study at a glance

Abstract

Cellular aging, driven by oxidative stress, mitochondrial dysfunction, and inflammation, is exacerbated by a high-glucose and high-lipid (HGHL) diet, leading to collagen degradation and skin aging. Psilocybin, a naturally occurring compound, has shown potential in reducing symptoms of aging. This study explores the protective effects of psilocybin on BJ-5ta fibroblasts exposed to HGHL, focusing on cellular viability, apoptosis, senescence, the inflammatory responses, and wound healing. First, fibroblasts were exposed to 25 mmol/L glucose and 400 µmol/L palmitic acid to establish cell aging. Then, psilocybin effects were tested in co- and post-treatment with HGHL. Post-treatment with psilocybin at 15 µmol/L (P15) and co-treatment with psilocybin at 10 µmol/L (P10) preserved cellular viability and decreased beta-galactosidase activity. P10 was most effective in reducing apoptosis and alleviating HGHL-induced S phase arrest. P15 also reduced senescence markers and decreased the expression of inflammatory cytokines IL-1β, IL-6, and COX-2. Additionally, psilocybin promoted nonsignificant fibroblast migration, and P10 co-treated with HGHL significantly upregulated elastin gene expression. These findings suggest that psilocybin’s antioxidative, anti-inflammatory, and regenerative properties make it a promising natural compound for reducing skin aging, particularly under oxidative stress conditions. Further research is needed to explore its long-term effects, optimal dosages, and clinical applications.