Researchers investigated psilocybin, a psychedelic compound found in hallucinogenic mushrooms, for its anti-aging properties. They found that it extends cellular and organismal lifespan, even when administered later in life [1].
From ancient times to contemporary therapies
Hallucinogenic mushrooms have a long history of use, reaching back to ancient times when people often used them for religious or spiritual reasons. Today, their naturally occurring psychedelic compound, psilocybin, has been investigated for its therapeutic value, especially in psychiatric and neurodegenerative diseases [2, 3].
“There have been a number of clinical studies that have explored the therapeutic potential of psilocybin in psychiatric conditions such as depression and anxiety; however, few studies have evaluated its impacts outside the brain,” said Dr. Louise Hecker, associate professor of medicine at Baylor and senior author of the study.
Extending cellular lifespan
Those researchers set out to test the effect of psilocybin on biological aging. In their cell culture studies, they used psilocin, the active metabolite of psilocybin and a product of psilocybin digestion.
First, they tested replicative senescence using human fetal lung fibroblasts. In these experiments, cells were allowed to grow and divide in the presence of psilocin until they reached replicative senescence and became unable to divide further.
Cells treated with higher doses of psilocin had cellular lifespan extended by 57% compared to untreated controls. Treated cells also had delayed senescence; decreased levels of cell cycle arrest, DNA damage, oxidative stress, and senescence markers; increased markers of proliferation and DNA replication; and increased levels of Sirtuin 1, a protein that plays an essential role in aging, metabolism, and stress responses.
Based on their results and the results of previous studies, the authors suggest that psilocybin, through interaction with serotonin receptors, induces the expression of the Sirtuin 1 gene (SIRT1), which increases antioxidant enzymes, leading to a reduction of oxidative stress and neuroprotection. Additionally, SIRT1, through the regulation of senescence, extends longevity.
These results suggest that psilocin impacts multiple aging-associated signaling pathways and processes, leading to delayed senescence and increased cellular lifespan.
The psilocybin-telomere hypothesis
This study was also the first to show experimental evidence supporting the “psilocybin-telomere hypothesis,” [4] which states that psilocybin can positively impact telomere length.
When cultured cells reached the senescent state, the untreated cells had reduced telomere length compared to young cells. However, that did not happen in psilocin-treated age-matched cells, which preserved their telomere length.
While these results shed light on the age-related molecular pathways affected by psilocybin, future studies are necessary to dive deeper to understand the molecular mechanism behind the positive impact of psilocybin on aging-related phenotypes and investigate some pathways and molecular processes that were not examined in this study, including the possible geroprotective impact of psilocybin on epigenetic changes, especially since psychedelic treatments were previously linked to chromatin remodeling and DNA methylation [5, 6].
Improved survival
The positive results of the cellular experiments prompted the researchers to test the effects of psilocybin on mice. They used aged (19-month-old) female mice, equivalent to 60-65 human years, and treated them with psilocybin once per month for 10 months, first with a low and later with a high psilocybin dose. After that time, the psilocybin-treated group reached median survival, and the remaining mice were euthanized.
Psilocybin significantly improved the survival of aged mice compared to untreated mice. It also improved overall fur quality, hair growth, and reduced white hair; however, this was not quantified.
“This is a very exciting and clinically relevant finding that suggests that even when intervention is initiated late in life, it can have dramatic impacts,” said Dr. Kosuke Kato, lead author of the study and assistant professor of medicine at Baylor.
Further optimization is needed
While these results are promising, there is a need to optimize further and test the possibility of initiating the treatment earlier in life, which can possibly lead to greater effects.
“It is important to note that additional research is needed to validate these findings in human studies,” Kato said. “There is still a lot to understand, including optimal dosing protocols that will lead to maximal efficacy. We also need to better understand the potential risks of long-term psilocybin treatment before this type of treatment is ready for public use.”
Future studies also need to address the sex-specific effect of psilocybin. Some studies reported sex-specific effects of psilocybin in rodents, but the results are inconsistent and need clarification [7].
To minimize the effect of sex as a variable, in this study, the researchers studied only female mice; therefore, there is a need to test whether the described effect is also present in male mice.
What’s promising is that psilocybin seems to have minimal adverse side effects and has received FDA’s designation as a breakthrough therapy: a “process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).”
Anti-aging potential
The researchers point out that their results, for the first time, show psilocybin’s impact on multiple hallmarks of aging (cellular senescence, telomere attrition, genomic stability, and altered intracellular communication) and suggest psilocybin’s potential as an anti-aging agent and a potential therapeutic for age-related diseases.
“Our findings open an exciting new chapter in psychedelic research beyond its neurological and psychological benefits,” Hecker says. “Psilocybin may represent a disruptive agent that promotes healthy aging. The next steps need to explore the therapeutic effects across multiple age-related diseases.”
Literature
[1] Kato, K., Kleinhenz, J. M., Shin, Y. J., Coarfa, C., Zarrabi, A. J., & Hecker, L. (2025). Psilocybin treatment extends cellular lifespan and improves survival of aged mice. npj aging, 11(1), 55.
[2] Raison, C. L., Sanacora, G., Woolley, J., Heinzerling, K., Dunlop, B. W., Brown, R. T., Kakar, R., Hassman, M., Trivedi, R. P., Robison, R., Gukasyan, N., Nayak, S. M., Hu, X., O’Donnell, K. C., Kelmendi, B., Sloshower, J., Penn, A. D., Bradley, E., Kelly, D. F., Mletzko, T., … Griffiths, R. R. (2023). Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA, 330(9), 843–853.
[3] Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., Bird, C., Blom, R. E., Brennan, C., Brusch, D., Burke, L., Campbell-Coker, K., Carhart-Harris, R., Cattell, J., Daniel, A., DeBattista, C., Dunlop, B. W., Eisen, K., Feifel, D., Forbes, M., … Malievskaia, E. (2022). Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. The New England journal of medicine, 387(18), 1637–1648.
[4] Germann C. B. (2020). The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging. Medical hypotheses, 134, 109406.
[5] de la Fuente Revenga, M., Zhu, B., Guevara, C. A., Naler, L. B., Saunders, J. M., Zhou, Z., Toneatti, R., Sierra, S., Wolstenholme, J. T., Beardsley, P. M., Huntley, G. W., Lu, C., & González-Maeso, J. (2021). Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice. Cell reports, 37(3), 109836.
[6] Inserra, A., Campanale, A., Cheishvili, D., Dymov, S., Wong, A., Marcal, N., Syme, R. A., Taylor, L., De Gregorio, D., Kennedy, T. E., Szyf, M., & Gobbi, G. (2022). Modulation of DNA methylation and protein expression in the prefrontal cortex by repeated administration of D-lysergic acid diethylamide (LSD): Impact on neurotropic, neurotrophic, and neuroplasticity signaling. Progress in neuro-psychopharmacology & biological psychiatry, 119, 110594.
[7] Tylš, F., Páleníček, T., Kadeřábek, L., Lipski, M., Kubešová, A., & Horáček, J. (2016). Sex differences and serotonergic mechanisms in the behavioural effects of psilocin. Behavioural pharmacology, 27(4), 309–320.
View the article at lifespan.io
