“Magic mushrooms”—long used by Indigenous communities in ceremonial contexts and popularized during the psychedelic heyday of the 1960s—are once again entering the mainstream, in large part for the potential clinical applications of their psychoactive component, psilocybin. Though scientific interest has thus far mainly focused on the use of psilocybin for treating psychiatric conditions like anxiety and depression, a recent study made headlines for findings that hinted at a role for psilocybin in aging-related processes. Specifically, authors Kato et. al. present data from human cells and aging mice that suggest psilocybin could potentially act as a lifespan-extending drug.1
Why psilocybin for aging?
The idea that psychedelic mushrooms can extend lifespan may seem like the sci-fi daydream of modern-day hippies, but it’s not without some level of scientific basis. Psilocybin—which is converted to the bioactive molecule psilocin in the body—has shown promising results in treating depression and anxiety through psilocin’s ability to bind to serotonin receptors (especially the 5-HT2A receptor), leading to alterations in mood, perception, and sense of self.2 Depression and anxiety are themselves thought to accelerate a number of aging processes, which has led to the theory that psilocybin might therefore slow aging by reducing psychological stress.
One of the aging processes believed to be exacerbated by psychological stress is telomere attrition. As we discuss in greater depth in AMA #76 (to be released tomorrow), telomeres are the protective DNA caps at the end of chromosomes and shorten each time a cell divides. Eventually, telomere shortening pushes cells into senescence, a hallmark of aging in which cells are still alive but are no longer growing and dividing (sometimes referred to as “zombie cells”), and the build-up of such cells can promote inflammation. Because psychological stress may accelerate telomere attrition, the “psilocybin-telomere hypothesis” therefore posits that psilocybin could preserve telomeres through a reduction of psychologic stress, and thus might slow aging.
But the serotonin receptors activated by psilocin aren’t just present in the brain; they’re scattered throughout the body, including in immune cells and the gut. This raises the possibility that psilocybin might have direct systemic effects in addition to potentially influencing aging through its psychological effects. Oxidative stress—a state in which the production of reactive oxygen species (ROS) outpaces the body’s ability to neutralize them—also promotes tissue damage and is a characteristic feature of aging, and it has been suggested that psilocin can reduce the release of ROS through activation of the 5-HT2A receptor.3 Oxidative stress can also lead to accelerated telomere attrition and chronic inflammation, so psilocybin-induced ROS reduction may affect aging through multiple mechanisms.
Put together, we see various pathways through which psilocybin has been hypothesized to slow aging, mainly resting on the slowing of telomere attrition via reduction in both psychological stress and oxidative stress. However, it is also a fragile hypothesis that relies on a chain of correlations and theoretical mechanistic connections. Each link is a leap of faith needing experimental validation and explanation of causal direction, prompting the Kato et. al. to investigate more deeply.
About the study
To put the psilocybin–telomere hypothesis to the test, the authors primarily relied on experiments conducted with human cells (lung fibroblasts) grown in a laboratory, supplemented by an additional proof-of-concept experiment in living, aged mice.
For cell culture experiments, human cells were treated with psilocin or vehicle (controls) and allowed to continue dividing until they reached a state of senescence, such that the number of divisions a cell underwent before reaching senescence could be regarded as the replicative “lifespan” of the cell. Compared to control cells, cells treated with psilocin at a concentration of 10 μM displayed an extension of cellular lifespan of 29%, while an even greater effect was observed in cells treated with a tenfold higher dose—a 57% extension relative to controls. These findings were further validated by reductions in cellular markers of cell cycle arrest (which slow or halt cell growth and division) and increased markers of proliferation in treated cells. Taken together, these results point to delays in cellular senescence when psilocin is applied directly to human cells.
Psilocin-treated cells also produced less ROS and exhibited longer telomeres. Across a wide range of concentrations (0.01 to 100 μM), psilocin led to dose-dependent reductions in ROS production in aged cells (60–63 days in culture) compared with controls, with the highest doses reaching a level of ROS at or below that of younger cells (0–4 days in culture). Likewise, while telomere length declined in control cells as they aged, psilocin-treated cells preserved their telomere length, and since these were cultured cells and thus not subject to the effects of psychological stress, we can conclude that psilocin can indeed influence telomere length through direct effects on peripheral cells—whether through the reduced ROS production or through a different, unknown mechanism.
But the experiment that caused the study to make headlines was a proof-of-concept survival experiment in 30 female mice. The authors treated these mice with oral psilocybin or vehicle once per month starting at 19 months old (roughly equivalent to a 60- to 65-year-old human). After 10 months of treatment, about 80% of the psilocybin group was still alive, compared with only 50% of controls. The psilocybin treated mice also appeared healthier, with darker, fuller coats and fewer patchy, gray areas.
Thus, in human cells, psilocin appeared to slow cellular aging across multiple related hallmarks—reduced senescence, lower oxidative stress, and preserved telomeres. In living animals, psilocybin increased the survival rate of older animals and improved visual signs of aging.
A flawed premise
On the surface, Kato et. al.’s results seem striking, but unfortunately, they’re built on the shaky foundation of a flawed mechanistic rationale. While it’s true that telomeres shorten with repeated cell divisions (which is partially offset by enzymes that rebuild telomeres), there’s little evidence that telomere length reliably predicts lifespan or that slowing the process of telomere attrition might enhance lifespan. Across species, telomere length has no consistent relationship to longevity: mice, for example, have much longer telomeres than humans but live only a few years. Even correlations with chronological age are weak. A 2021 meta-analysis of telomere length in 98 species found only a very modest inverse relationship with age, and only in adults.4 In juveniles, there was no correlation at all, and the analysis didn’t even find a clear difference in telomere length between adults and juveniles. In other words, telomere length may reflect how many times a cell has divided, but it is not a reliable marker of aging.
What to make of apparent lifespan effects?
Despite the shaky premise that preserving telomere length will extend lifespan, the data from this study did indeed show that more animals survived to the end of the experiment if they were given psilocybin instead of placebo—an observation that is hard to ignore. And there are certainly plenty of other paths through which psilocybin might accomplish such an effect, independent of telomeres. However, it’s worth noting that this experiment lacked a certain degree of rigor and completeness typically expected for lifespan extension tests.
For one thing, the researchers imposed a forced endpoint. Once 50% of the control animals died, they stopped the study. That means we don’t know the true median lifespan of the psilocybin group (at what age 50% of those animals had died), nor do we know whether the treatment extended maximum lifespan (how long the longest-lived animals survived). Without those numbers, the claim that psilocybin is a bona fide lifespan-extending drug is premature at best. What the study really shows is not that psilocybin pushed the ceiling of aging outward, but simply that fewer treated mice died over the treatment period under the study’s conditions—an important distinction when we’re talking about interventions that claim to slow aging.
But let’s say psilocybin truly did extend lifespan in these mice—we still must leap hurdles related to translating these results to humans. The most obvious is dosing. The animals were given quite large amounts of psilocybin, far beyond what most humans would find tolerable. At 15 mg/kg, the monthly dose given to these mice translates (via standard allometric scaling to account for differences in metabolism) to about 1.2 mg/kg in humans—roughly 72 mg for a 60 kg person. For context, current therapeutic trials of psilocybin typically use about 25 mg, and 50 mg is considered a “hero dose” in psychedelic communities. In other words, the mouse regimen would amount to taking a hero dose once a month, every month, for years on end.
Why did they dose the animals at such high amounts? The researchers started by correcting for differences in metabolism using allometric scaling, then added a second adjustment based on the half-life of the drug seen in mice compared to in humans—essentially correcting twice for the same factor of faster drug metabolism in mice. This approach may be defensible for proof-of-principle tests in which the goal is to maximize the likelihood of seeing an effect, but it raises obvious questions about translation, as the regimen used here is unlikely to map onto any realistic scenario for human use.
Not proof, but not nothing
Despite its methodological limitations and shaky rationale, this study does serve an important purpose as exploratory research—raising interesting questions for further investigation.
First, what’s the true mechanism at play? By acting on 5-HT2A receptors, psilocybin alters stress reactivity and may reduce systemic inflammation and oxidative stress. Might this be a more important mechanism than slowing telomere shortening? Or perhaps the lifespan effect in mice has less to do with the apparent cell-autonomous effects on ROS and instead relates more to the psychological effects of buffering stress, which leads to a critical question: must the psychological effects be experienced for the physiological benefits to emerge? Could a non-hallucinogenic analog produce the same downstream changes without the psychedelic trip?
Second, how does psilocybin stack up against a “gold standard” geroprotector like rapamycin? Rapamycin has extended both median and maximum lifespan across sexes, strains, and labs, with clear functional benefits along the way. Psilocybin, by contrast, has one small, unreplicated study, in a single sex, with a forced endpoint. For now, it’s not in the same league—but could future experiments put it there? Perhaps if psilocybin is subjected to the rigorous testing of the Interventions Testing Program (ITP), we may eventually have reason to put more faith in its alleged lifespan enhancement effects.
Finally, what about functional outcomes? Survival curves and coat color only scratch the surface of aging biology. Does psilocybin help to preserve lean mass and reduce frailty in older animals? What about improvements in cognitive function, or maintenance of immune competence? Without these types of readouts, we’re left guessing whether the mice simply lived longer—or whether they actually lived better.
The bottom line
Studies on psilocybin inevitably spark debate, probably because it has been deemed a Schedule I substance (classified as having “high abuse potential” and “no accepted medical use,” though both of these classifications have come into serious question). As such, some dismiss the results outright, while others hail them as heralding a new era for psychoactive medicine. The reality, as always, is more nuanced.
This study is intriguing because its signals all point in the “right” direction: longer-lived cells in vitro, reduced oxidative stress, preserved telomeres (whether or not that means anything), and greater survival in aged mice. But pointing in the right direction is not the same as proof. The mouse experiment was not designed to test lifespan rigorously, the telomere rationale is shaky, and the dosing strategy raises obvious translational challenges.
Still, it opens up worthwhile lines of inquiry. If psilocybin’s effects are really driven by stress buffering and serotonergic signaling, that could add an important dimension to how we think about mental health and aging. The question now is whether these early, suggestive findings will hold up under the weight of more careful experiments. Until then, psilocybin remains an exciting molecule with therapeutic promise—but not yet a proven player in the longevity space.
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References
1. Kato K, Kleinhenz JM, Shin YJ, Coarfa C, Zarrabi AJ, Hecker L. Psilocybin treatment extends cellular lifespan and improves survival of aged mice. NPJ Aging. 2025;11(1):55. doi:10.1038/s41514-025-00244-x
2. Remot F, Ronget V, Froy H, et al. Decline in telomere length with increasing age across nonhuman vertebrates: A meta-analysis. Mol Ecol. 2022;31(23):5917-5932. doi:10.1111/mec.16145
3. Goldberg SB, Pace BT, Nicholas CR, Raison CL, Hutson PR. The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. Psychiatry Res. 2020;284(112749):112749. doi:10.1016/j.psychres.2020.112749
4. Wiens KR, Brooks NAH, Riar I, Greuel BK, Lindhout IA, Klegeris A. Psilocin, the psychoactive metabolite of psilocybin, modulates select neuroimmune functions of microglial cells in a 5-HT2 receptor-dependent manner. Molecules. 2024;29(21):5084. doi:10.3390/molecules29215084
