Psilocybin, a naturally occurring psychedelic compound, is found in over 200 species of mushrooms, commonly known as "magic mushrooms," with a long history of use in indigenous cultures for religious, healing, and divinatory purposes, particularly in regions like Mexico and South America. Chemically, psilocybin is rapidly metabolized into psilocin, which acts as a serotonin 2A receptor agonist, producing profound alterations in consciousness. In clinical settings, psilocybin is administered as a synthesized compound under tightly controlled conditions, involving extensive participant preparation and professional support to ensure safety and maximize therapeutic outcomes. As discussed in FoundMyFitness episode #30 with the late Dr. Roland Griffiths, a leading psychopharmacologist at Johns Hopkins University, psilocybin's effects are remarkable for their depth and durability, offering significant potential for mental health treatment.

The most prominent clinical uses of psilocybin include addressing anxiety and depression, particularly in patients with life-threatening cancer diagnoses, where a single dose has been shown to produce rapid and sustained reductions in symptoms, lasting up to six months.. Emerging research also suggests efficacy in treatment-resistant depression, smoking cessation, and potentially other conditions like alcoholism, cocaine dependence, PTSD, and OCD, driven by psilocybin's ability to foster neuroplasticity and reorganize psychological perspectives. Its well-known effects include inducing mystical-type experiences characterized by a sense of interconnectedness, sacredness, and authenticity, which participants often rate among the most meaningful of their lives. These experiences, mediated by decreased activity in the brain's default mode network and enhanced neurogenesis, lead to lasting improvements in mood, behavior, and openness, positioning psilocybin as a promising tool for mental health and potentially broader therapeutic applications, though its Schedule I status underscores the need for cautious, regulated use.

Psilocybin and Lifespan Extension

"Collectively, these results reveal something novel and exciting about psilocybin—it appears to be having direct effects on mechanisms of cellular aging that are independent of its psychedelic properties." Click To Tweet

What if psilocybin's ability to improve mental health, reduce chronic stress, and foster fewer negative emotional states indirectly mitigate physiological aging processes? That's exactly what a new study suggests— it might be time to think about psilocybin as a "longevity molecule."^[1]

Psilocin and Psilocybin Extend Survival in Cells and Mice

The study involved in vitro and in vivo components—investigating psilocybin's effects in isolated cells and in mice.

For the in vitro study, human lung and skin cells were exposed to psilocin—the metabolite that's produced after psilocybin is ingested and metabolized by the body. Other cells were exposed to a control treatment, and both treatments continued until the cells reached replicative senescence—a state where cells become "old," stop dividing, and enter a permanent growth arrest. It occurs after a finite number of cell divisions, often due to the progressive shortening of telomeres (protective DNA caps at chromosome ends) with each division. Senescence is a well-recognized "hallmark of aging."

Psilocin extended the lifespan of cells by 29%, effectively slowed the exhaustion of their replicative capacity, increased the number of cell doublings, and reduced the cells' doubling time. Cellular lifespan extension was enhanced even more when a higher dose (10x the initial dose) was used, with a 57% increase observed compared to untreated cells. Psilocin also delayed cellular senescence.

Even more remarkable was the impact of psilocin on the "hallmarks of aging" and age-related cellular changes. For one, psilocin reduced the activity of β-gal and markers of cell cycle arrest and increased the activity of markers of cell proliferation and DNA replication. Psilocin also elevated sirtuins (i.e., SIRT1) and reduced markers of DNA damage and oxidative stress in a dose-dependent manner.

Lastly, psilocin reduced one of the most well-established markers of cellular aging—telomere shortening. While the telomeres of the untreated cells were naturally shortened during cell senescence (as occurs in human aging), the telomeres of the psilocin-treated cells were preserved.

For the in vivo study, 19-month-old female mice (which corresponds to about age 60–65 in humans) were given a monthly dose of psilocybin for 10 months: 5 mg/kg for the first month and then 15 mg/kg thereafter.

During the treatment period, 80% of mice who were given psilocybin survived while only 50% of the non-treated mice survived—a meaningful difference in survival rate between the two groups. Furthermore, psilocybin enhanced some physical features of the mice, including improvements in fur quality, hair growth, and less white hair and hair greying. So not only did they live longer, but they looked younger too.

Collectively, these results reveal something novel and exciting about psilocybin—it appears to be having direct effects on mechanisms of cellular aging that are independent of its psychedelic properties.

However, the mind-altering nature of psilocybin might also indirectly impact how we age.

Tying Psilocybin's Anti-Aging Effects to Depression and Mental Health

"By inducing positively valenced, and sometimes even life-altering, psychological experiences, psilocybin may leave"quantifiable marks at the molecular genetic and epigenetic level." Click To Tweet

When we talk about aging and its causes, the focus is typically on intrinsic biological processes, the role of physical inactivity, and the effects of diet and other lifestyle factors. Of course, each of these plays a profound role in how quickly (or how slowly) we age and therefore, our healthspan and lifespan.

But mental health is also crucial for healthy aging. Indeed, depression and anxiety have been linked to shorter telomeres, a greater risk of chronic diseases, and even mortality. This indicates that psychological (dis)tress likely accelerates biological aging at the cellular level. On the other hand, positive psychological states are associated with telomere lengthening and lower rates of disease.

This is where psilocybin enters the picture as a potential longevity molecule.

The Psilocybin-Telomere Hypothesis posits that psilocybin may have a measurable, beneficial effect on biological aging by lengthening telomeres. The hypothesis is based on two well-established premises. The first is that depression and chronic stress are associated with shortened telomeres, and shorter telomeres are linked with age-related diseases and mortality. Second, psilocybin has clinically documented antidepressant and stress-reducing effects. Therefore, if psilocybin reduces depression, and depression shortens telomeres, then psilocybin may help preserve or even lengthen telomeres. By inducing positively valenced, and sometimes even life-altering, psychological experiences, psilocybin may leave "quantifiable marks at the molecular genetic [and] epigenetic level."

Though it's just a hypothesis, several lines of evidence support the idea that psilocybin exerts biological anti-aging effects, with pathways including:

Reduced rumination and depression, both of which are linked to telomere shortening. Downregulation of the default mode network (DMN), which is overactive in depression. Increased neurogenesis and neuroplasticity, particularly in the hippocampus. Elevated levels of BDNF to support neuron survival and greater telomerase activity. Reduced inflammation and oxidative stress, which are implicated in telomere erosion. Modulation of the serotonin system (the 5-HT2A receptor and serotonin transporter gene SLC6A4), which is linked to depression and stress resilience.

Lending further support to this hypothesis is research on meditation—an intervention that induces similar states of consciousness to psilocybin therapy—which also prevents telomere attrition and even lengthens telomeres in some cases. The late Dr. Roland Griffiths refers to psilocybin-assisted therapy as a "crash course" in meditation, abruptly shifting consciousness to reveal alternative ways of perceiving reality. Dr. Elissa Epel and others propose that "some forms of meditation may have salutary effects on telomere length by reducing cognitive stress and stress arousal and increasing positive states of mind and hormonal factors that may promote telomere maintenance."

While psilocybin and meditation aren't identical in their therapeutic effects, it's clear that our psychological state influences our biology, and therefore our speed of aging.

Conclusion

Regardless of your stance on psychedelics, this study is a tantalizing glimpse into new frontiers for healthy aging. It suggests psilocybin could be a novel tool in combating age-related decline.

However, it's critical to note that psilocybin remains a Schedule I controlled substance in many jurisdictions, including the United States, where it is illegal outside of approved research settings due to its psychedelic properties. While the science is exciting, any exploration of psilocybin's therapeutic potential will have to await further studies and regulatory changes.

The interconnectedness of mind and body when it comes to health is indisputable, and that's perhaps what makes psilocybin and other psychedelic-assisted therapies so intriguing as longevity interventions, even though we might not think of them as such.

Whether it's psychedelics or meditation, our subjective experiences are intimately tied to biological aging. When you "change your mind," you also change your cells.