Psilocybin alleviates high-glucose and high-lipid-induced skin aging in BJ5Ta fibroblasts
Can psilocybin protect skin cells from premature aging due to a poor diet?
This preclinical laboratory study investigated whether psilocybin could protect human dermal fibroblasts (the cells responsible for producing collagen and elastin) from metabolic stress designed to mimic some of the cellular changes associated with skin ageing. The researchers exposed the cells to high glucose and palmitic acid before assessing the effects of psilocybin.
The study found that psilocybin:
Improved cell survival, helping fibroblasts withstand metabolic stress.
Reduced markers of cellular senescence, suggesting fewer cells entered an aged or dysfunctional state.
Reduced apoptosis (programmed cell death), particularly when psilocybin was present during the stress exposure.
Lowered inflammatory signalling, with reduced expression of pro-inflammatory markers including IL-1β, IL-6 and COX-2.
Increased elastin (ELN) gene expression, indicating a potential influence on extracellular matrix biology, although this did not demonstrate increased elastin protein or improvements in skin structure.
Did not significantly improve cell migration (wound-healing capacity), suggesting not all aspects of fibroblast function were affected.
The findings suggest that psilocybin may help protect human skin fibroblasts from metabolically induced cellular stress by reducing inflammation, cellular senescence and programmed cell death. However, this was a cell culture study, not a human clinical trial, so the results cannot be interpreted as evidence that psilocybin slows skin ageing or improves skin health in people.
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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