In this episode, Dr. Matt Kaeberlein, discusses the emerging evidence that psilocybin, the psychedelic compound found in magic mushrooms, may have positive impacts on the biology of aging and longevity. He notes a recent paper published in NPJ Aging that reported psilocybin treatment extends cellular lifespan and improves survival in aged mice.

Psilocybin acts as a non-selective agonist of serotonin (5-HT) receptors, leading to long-lasting activation of these receptors and producing hallucinogenic effects. The host explains the role of serotonin signaling in regulating various physiological processes.

The paper first examined the impact of psilocin (the active metabolite of psilocybin) on cellular senescence in fibroblast cultures, finding a delay in replicative senescence. However, the host expresses some skepticism about the strength of this in vitro data, noting limitations in the experimental design.

The more compelling data in the paper is the lifespan extension observed in aged mice treated with psilocybin. The host compares these results to his own lab's work on rapamycin and finds the psilocybin lifespan effects to be quite robust, despite the experiment being incomplete.

Matt also speculates on potential mechanisms by which psilocybin could be impacting longevity, including through modulation of SIRT1, telomere length/telomerase, serotonin signaling, the NRF2 pathway, and brain-derived neurotrophic factor (BDNF). He notes that these mechanisms are not mutually exclusive and may involve complex interactions.

While cautioning against premature use of psilocybin for longevity purposes, Matt expresses optimism about the potential of psilocybin as a longevity-promoting compound and calls for further research to elucidate the underlying mechanisms, including whether the hallucinogenic effects are necessary for the observed benefits.