From Mood Stabilizers to Magic Mushrooms: What Three Repurposed Drugs Reveal About Telomere Biology’s Role in Aging

Recently, three intriguing academic papers have made the case that three different drugs may produce longevity-enhancing effects, quite apart from the unrelated conditions they’re now being used to treat. I’ve written posts about two of these drugs, lithium, widely used to treat bipolar disorder, and Zetia (ezetimibe), a second-line cholesterol-lowering drug. The third one may raise some eyebrows, psilocybin, the active ingredient in mind-altering “magic mushrooms.”

One obvious take-away is that investigating drugs already being used (in the case of psilocybin, a strictly controlled Schedule 1 drug, in a backchannel way) is probably an effective strategy for identifying potential new “geroprotectors.” It is, after all, how metformin and rapamycin came into the longevity fold. Repurposing “old” drugs sidesteps the biggest obstacle in the field, the fantastic cost of doing randomized controlled trials for brand-new drugs, which Big Pharma won’t shell out for, not unless there’s a potentially lucrative molecule to patent. 

But that’s not what really interests me here. What does is the role that telomere biology plays in all three studies, as a common denominator explanation for how such different molecules seem to yield similar benefits in slowing down aging at the cellular level, especially in the brain, in the case of two of the three drugs, protecting against Alzheimer’s disease.

First, a little background. Telomeres are the repetitive DNA sequences that cap the end of our chromosomes. For cells that frequently divide – think skin, gut, lungs, crucially the immune system – every cell division shortens these protective caps. Eventually, a critical threshold may be reached, triggering most of the merciless “Hallmarks of Aging,” usual suspects like cellular senescence, genomic instability, mitochondrial dysfunction that underlie the chronic “diseases of aging” and, we think, taken together, drive the entire aging process.

In the studies looking at lithium, psilocybin, and ezetimibe, these three different molecules increased (or in case of ezetimibe, may have increased) the cellular expression of telomerase, the enzyme responsible for limiting the inevitable loss of telomere length over the course of the lifetime. Last year, a landmark study in Cell offered up persuasive evidence that boosting telomerase reversed aging (yes, in mice), not only by allowing proliferative cells to keep dividing but also by operating at the epigenetic level, turning down the activation of genes responsible for unleashing those destructive Hallmarks. To my mind, the new drug studies lend more credence to what the Cell paper implied, that telomerase activation may hold the key to unlocking the conundrum of human aging.

Let’s get down to cases. The paper published this August in Nature by a team of Harvard researchers, “Lithium deficiency and the onset of Alzheimer’s disease,” shows lithium activating telomerase in human cell lines in vitro. The complementary animal studies allowed the researchers to elucidate a mechanism to explain how upregulated telomerase could protect brain function. A novel form of lithium, lithium orotate, effective at very low doses, inhibits a protein kinase, GSK-3beta, which indirectly pumps up telomerase. That in turn reduces cell senescence, allowing cells to continue to divide and may contribute to a basket of other mice neurological benefits. You might call them the Hallmarks of Anti-Aging: reducing oxidative stress, promoting the growth of new neurons in the hippocampus, protecting the mitochondria and the like. And yes, the mice, suffering from Alzheimer’s-like symptoms when their diets were completely drained of lithium, were fed the lithium orotate and got their memories back. 

In 2020 a maverick brain scientist published a paper that essentially dared the research establishment to prove him wrong. He hypothesized that psilocybin could, in a verifiable genetic way, slow brain aging. His deduction was as follows: Psilocybin has an estimable therapeutic track record in the treatment of mental health conditions like PTSD and age-related depression. Good mental health has been correlated with long telomeres and/or slower telomere attrition. Meditative practices have been shown to enhance telomere stability and psilocybin has been well known to induce altered mental states that might be considered meditative. Ergo, psilocybin helps slow down telomere attrition and brain aging.

This past July, a team of Emory and Baylor researchers published a paper in npj Aging, “Psilocybin treatment extends cellular lifespan and improves survival of aged mice” that not only proved that the “Psilocybin-Telomere Hypothesis” was correct but in the process set the longevity medicine community back on its ears.  In vitro, human fibroblasts dosed with psilocin, the active metabolite of psilocybin, had lower levels of oxidative stress, maintained their telomere length and survived 57% longer than the undosed controls. More remarkably, mice dosed with psilocybin lived 15-20% longer.  

The Emory-Baylor team did not specifically investigate an Alzheimer’s application, but it stands to reason that what’s good for brain resilience more broadly can only help with AD. A larger unanswered question is whether micro-dosing psilocybin, a more practicable “non-trippy” form of longevity therapy, will confer anywhere near the same benefits as the larger experimental doses.

Earlier animal research had shown that Zetia (ezetimibe), the anti-cholesterol drug, could extend the life of tiny c. elegans worms by 20%, likely by providing a healthy (or “hormetic”) stress that upregulated protective stress genes. But “off-label” interest in the drug spiked with the publication in July of last year of an observational study by a group of University of Arkansas researchers that analyzed over 900,000 patient records. They found that Zetia users developed Alzheimer’s over seven times less frequently than non-users. (That’s relative risk of course; in absolute risk terms, the Zetia group was roughly 0.7% less likely to develop the disease.) While none of the ezetimibe research has measured telomeres or telomerase, an inference is highly plausible, that by reducing oxidative stress and LDL, both enemies of your telomeres, Zetia can slow cellular aging.

To my mind, these three studies and these three drugs give us a glimpse into the future of longevity medicine, where our telomere system is both a target for therapeutic intervention and a way to measure their efficacy. In the here and now they provide a theoretical rationale for repurposing existing drugs to reduce the risk of Alzheimer’s, likely more effectively and certainly with greater safety than the standard pharma armamentarium. Take me for example. I carry the APOe4 gene mutation that puts me at greater risk for AD. I’m now microdosing lithium orotate, have experimented with microdosing psilocybin and I’m considering going back on Zetia, both for LDL reduction and for AD protection. (I didn’t like the GI side effects the first time around). Oh yes, I and most of my patients take TA -65, a telomerase activator supplement, originally developed by the pharmaceutical industry. Is this a mainstream medical approach? Hardly. But I predict over the next decade, we’ll have plenty of company.

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Aron L, Ngian ZK, Qiu C, et al. Lithium deficiency and the onset of Alzheimer’s disease. Nature. Published online August 6, 2025:1-10. doi:10.1038/s41586-025-09335-x

Akshatha Ganne, et al. Ezetimibe Lowers Risk of Alzheimer’s and Related Dementias over Sevenfold, Reducing Aggregation in Model Systems by Inhibiting 14-3-3G::Hexokinase Interaction. Aging Biology 2024. June 26, 2024. doi: 10.59368/agingbio.20240028

Kato, K., Kleinhenz, J.M., Shin, YJ. et al. Psilocybin treatment extends cellular lifespan and improves survival of aged mice. npj Aging 11, 55 (2025). doi: 10.1038/s41514-025-00244-x

Germann CB. The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging. Med Hypotheses. 2020 Jan;134:109406. doi: 10.1016/j.mehy.2019.109406

Shim HS, Iaconelli J, Shang X, et al. TERT activation targets DNA methylation and multiple  aging hallmarks. Cell. Published online June 13, 2024:S0092-8674(24)00592-0. doi:10.1016/j.cell.2024.05.048