Can psilocybin, the active compound found in certain mushrooms, help protect skin cells from premature aging caused by poor diets?
This in vitro study aimed to investigate whether psilocybin could protect human skin fibroblasts against cellular ageing induced by high-glucose (25 mmol/L) and high-palmitic-acid (400 µmol/L) exposure. Using both preventive co-treatment and post-treatment approaches, the researchers found that psilocybin (10–15 µmol/L) improved cell viability and significantly reduced β-galactosidase activity, a marker of cellular senescence. Co-treatment with 10 µmol/L was particularly effective in reducing apoptosis and restoring cell-cycle progression, while post-treatment with 15 µmol/L reduced the expression of several inflammatory genes. Psilocybin also significantly increased elastin gene expression in the co-treatment group, but did not consistently restore collagen gene expression, and improvements in fibroblast migration were not statistically significant. Overall, the findings suggest potential protective effects against metabolically induced cellular senescence, but the study was conducted in an immortalised fibroblast cell line and does not demonstrate anti-ageing effects in human skin.
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.
Farzaneh Norouzkhani, Esmaeel Ghasemi Gojani, Bo Wang, DongPing Li, Salma Shujat, Aadarsh Shrestha, Rocio Rodriguez-Juarez, Olga Kovalchuk, and Igor Kovalchuk. 2025. Psilocybin alleviates high-glucose and high-lipid-induced skin aging in BJ5Ta fibroblasts. Biochemistry and Cell Biology. 103: 1-15 Read Paper
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