Psilocybin decelerates cellular senescence

Abstract Psilocybin is the psychoactive substance contained in the psilocybe(hallucinogenic) mushroom, which has received considerable attention among the scientific community in recent years. Human studies have demonstrated that even a single-dose of psilocybin can improve debilitating physical and psychological symptoms with durable long-term effects. >136 clinical studies with psilocybin have been completed or are ongoing for various indications, including psychiatric, neurodegenerative, chronic pain, and more. However, despite considerable clinical evidence for the therapeutic effects, the underlying molecular mechanisms responsible for its beneficial actions remain enigmatic. Studies with psilocybin have overwhelmingly focused on neurological impacts and/or behavioral outcomes; however, few studies have evaluated other mechanisms by which it exerts beneficial effects. It has recently been hypothesized that psilocybin may exert beneficial effects on aging; however, no studies have experimentally investigated the impact of psilocybin on senescence(definition)/aging. Using a previously validated human cell model of replicative senescence in vitro, cells were treated with psilocybin continuously throughout their replicative cellular lifecycle. Psilocybin treatment led to a dose-dependent decrease in cell-cycle arrest markers, increased markers of DNA replication and proliferation, reduced senescence-associated secretory phenotype (SASP), and reduced oxidative stress levels. Further, psilocybin did not demonstrate senolytic activity. Overall, these data are the first experimental evidence suggesting that psilocybin may decelerate the process of cellular senescence. Given that senescence and inflammation contribute to the pathogenesis of numerous age-related diseases, these studies could lay the foundation for the use of psilocybin as a therapeutic strategy for many age-related disease indications and/or as a geroprotective agent.