Psilocybin treatment extended lifespan and preserved telomeres in aged mice, suggesting potential as a geroprotective intervention.
A study from Emory University and Baylor College of Medicine has drawn attention for placing a compound more often associated with introspective journeys and psychedelic therapy firmly into the realm of geroscience. Psilocybin – the naturally occurring hallucinogen found in certain fungi – and its active metabolite psilocin were shown to extend cellular lifespan and improve survival outcomes in aged mice. The findings, published this month in npj Aging, represent a shift from psilocybin’s established psychiatric focus to its potential systemic and cellular effects on aging pathways.
According to the authors, the research provides “the first experimental evidence suggesting that psilocybin may impact multiple hallmarks of aging”, and offers direct support for the previously proposed “psilocybin–telomere hypothesis” – the notion that serotonergic interventions may preserve telomere length and, by extension, biological youth [1].
Longevity.Technology: That a compound best known for inducing transcendence might now be linked to extending lifespan in aged mice is the sort of twist that could only happen in geroscience – a field already accustomed to its fair share of biological paradox. This study is quietly significant; not only is it the first to show psilocybin’s potential geroprotective effects, but it does so using late-life administration, a rare and clinically relevant choice in a field that often defaults to youthful interventions. There’s also the tantalizing suggestion of epigenetic modulation – long hypothesized as a route through which psychedelics deliver durable benefit – now nudging its way into aging biology.
Of course, psilocybin remains a Schedule I substance in the United States, meaning the regulatory landscape remains difficult to navigate – slow-moving, opaque, and still at odds with the direction of the science. The data are early, and mouse fur is not human skin, but one suspects longevity biotech will now be watching closely – cautiously, perhaps, but with growing interest in whether this unlikely molecule may yet find a second act as a systemic aging intervention.
Cellular effects and telomere preservation
The study employed a well-established in vitro model using human lung fibroblasts exposed to psilocin across multiple passages. Compared with controls, treated cells demonstrated a delay in the onset of senescence, longer cumulative population doubling, and reduced markers of oxidative stress. Notably, telomere length was preserved in the treated group – a finding that adds empirical weight to earlier theoretical models. The authors noted “decreased levels of NADPH oxidase-4 (Nox4)… and increased nuclear factor erythroid 2-related factor 2 (Nrf2)”, suggesting a shift in redox balance in favor of cellular maintenance and repair [1].
The results were dose-dependent: higher concentrations of psilocin yielded greater extensions in lifespan without triggering oncogenic transformation. A second cell model using adult human skin fibroblasts replicated the findings, lending cross-tissue plausibility to the proposed mechanisms [1].
Animal data and geroprotective implications
To assess systemic effects, the researchers treated 19-month-old female mice – an age equivalent to 60–65 in human years – with monthly doses of psilocybin over a ten-month period. At study endpoint, survival was significantly higher in the treatment group (80% vs 50%), and although qualitative, visual assessment suggested improved fur quality and reduced hair whitening [1].
“Even when the intervention is initiated late in life in mice, it still leads to improved survival, which is clinically relevant in healthy aging,” said Dr Louise Hecker, senior author of the study and now associate professor at Baylor College of Medicine. She added: “Most cells in the body express serotonin receptors, and this study opens a new frontier for how psilocybin could influence systemic aging processes, particularly when administered later in life [2].”
This late-life initiation sets the study apart; most lifespan-extension trials begin in young adult animals and leave questions of translatability to older human populations unaddressed.
“This study provides strong preclinical evidence that psilocybin may contribute to healthier aging – not just a longer lifespan, but a better quality of life in later years,” said Dr Ali John Zarrabi, co-investigator and director of psychedelic research at Emory’s Department of Psychiatry. “These mice weren’t just surviving longer – they experienced better aging [2].”
More than mood
Psilocybin has long been studied for its psychological effects, particularly in treatment-resistant depression, addiction and end-of-life anxiety. But its interaction with the 5-HT2A receptor – expressed not only in the brain, but in fibroblasts, endothelial cells, macrophages and other peripheral tissues – points to a wider biological influence. In this study, psilocin increased expression of SIRT1, a well-known regulator of aging, metabolism and cellular stress resistance [1]. That SIRT1 is also implicated in the beneficial effects of calorie restriction and NAD+ boosting compounds may explain part of psilocybin’s appeal as a multi-modal aging intervention.
The authors acknowledge that while their findings are encouraging, they are also preliminary. “Although our in vitro studies suggest that psilocin-mediated cellular lifespan extension did not result in oncogenic transformation,” they write, “future research should rigorously assess the potential impacts of long-term psilocybin treatment in vivo on cancer incidence and/or progression [1].”
Mechanisms and epigenetics
Among the more speculative but intriguing proposals is that psilocybin’s effects may be epigenetically mediated – that is, delivered not through traditional drug-receptor activity alone, but via changes to DNA methylation, chromatin remodeling or transcriptional plasticity. This would mirror findings in psychedelic neuroscience, where a single dose of psilocybin has been shown to produce long-lasting structural and functional brain changes. Whether similar epigenetic fingerprints are found in peripheral or senescent cells remains to be seen.
A convergence of aging and mental health research
While the psychological benefits of psilocybin are increasingly well documented, this study supports a broader hypothesis gaining traction across geroscience – that mental health and biological aging are not independent, but interlinked through shared inflammatory, oxidative and epigenetic mechanisms. If true, then a treatment improving mood might also modulate systemic resilience; conversely, interventions targeting senescence may ultimately influence affective states. The line between neuroplasticity and longevity may be thinner than once thought.
Regulation and research friction
Despite FDA ‘breakthrough therapy’ designation for psychiatric indications, psilocybin’s Schedule I classification in the US continues to impede research. The authors note that this has created a bottleneck in securing funding and conducting translational studies. As the compound moves further into medical and aging-related contexts, the gap between regulatory framework and scientific potential is likely to become increasingly untenable.
Unlikely candidate, growing interest
The study’s mix of mechanistic detail, behavioral relevance and late-life intervention is likely to attract attention from longevity researchers and translational biotechs alike – particularly those pursuing multi-target therapeutics. Psilocybin is not the only serotonergic compound under examination, but it may now have the most compelling dual profile: cognitive benefit on the one hand, and cellular protection on the other.
That the geroscience community may soon find itself debating psychedelic treatment protocols alongside senolytics and sirtuin activators is not without irony; but if the evidence continues to build, the field may need to expand its definitions. Whether psilocybin belongs in the same therapeutic class as rapamycin or metformin remains an open question – but it is increasingly difficult to exclude it from the conversation.
Against the grain
Aging is rarely reversed by the usual suspects, and the emergence of psilocybin as a candidate geroprotector may reflect a deeper shift in how longevity research defines intervention. Less about fixing what has broken, and more about amplifying the body’s ability to maintain equilibrium – psychobiology and metabolism, telomeres and touchpoints of the mind – these overlaps are beginning to look less incidental, and more like a new direction of travel.
[1] https://www.nature.com/articles/s41514-025-00244-x
[2] https://news.emory.edu/stories/2025/07/hs_psilocybin_aging_study_10-07-2025/story.html
