Having spent some time working on aging research before transitioning to biotech, this paper genuinely excited me in a way that few studies have recently. The longevity field is littered with compounds that work beautifully in vitro but fail spectacularly in vivo - seeing psilocybin deliver both cellular lifespan extension AND improved survival in aged mice is remarkable.
What strikes me most is the mechanistic plausibility. The SIRT1 upregulation, reduced oxidative stress, and telomere preservation they observed align perfectly with what we know about successful aging interventions. When I was working on senescence research, we’d get compounds that would extend cellular lifespan by targeting one pathway, but they’d often have off-target effects that negated benefits in whole organisms.
The dosing strategy here is particularly clever - starting with 5mg/kg for acclimation, then monthly 15mg/kg treatments. That mirrors what we’re seeing in clinical trials for depression, but applied to aging. I remember being skeptical when colleagues first suggested psychedelics might have systemic anti-aging effects beyond their neurological benefits, but the serotonin receptor distribution throughout the body makes this increasingly plausible.
The survival curve (80% vs 50%) is the kind of effect size that gets my attention. In aging research, we’re usually thrilled with 10-20% lifespan extension. But starting treatment at 19 months (equivalent to 60-65 human years) makes this especially compelling - most aging interventions need to start early in life to be effective.
My main concern is the limited exploration of potential downsides. Delayed senescence can be a double-edged sword - those cells that keep proliferating longer might accumulate DNA damage that wasn’t detected in their short-term assays. We need much longer studies to understand cancer risk.
Still, given psilocybin’s remarkable safety profile and the FDA’s breakthrough therapy designation, this opens fascinating possibilities for combining psychedelic therapy with longevity medicine. Imagine treating both the psychological burden of aging and its biological mechanisms simultaneously.
One catch is both of those dosing levels are relatively large. This isn't toxic in the classic sense, but those are both heroic dosages on the mental effects side. I think this is like 20-80 grams of dried shrooms.
> The dosing strategy here is particularly clever - starting with 5mg/kg for acclimation, then monthly 15mg/kg treatments. That mirrors what we’re seeing in clinical trials for depression, but applied to aging.
15mg/kg seems like a lot, though. 15mg per person is a 'common' dose for a human. I don't know what the mapping between mice and humans is, but tripping on 1500mg of psilocybin once a month would be pretty taxing for me.
What a wild coincidence if true. Unless somehow the psychoactive effects are caused by the same thing... and how wild that would be considering the effect of the drug is to put you back into the state of in-the-moment wonder as if a child again!
Exercise, healthy diet, caloric restriction, adequate sleep, and stress management have also all had been shown to extend cellular lifespan and improve survival of aged mice - and humans.
One sees many of these kinds of papers about X or Y doing this or that incredible feat of life extension in mice. The problem is that aside from many of these papers possibly having some dubious methodology, the subjects are mice. That's some seriously different physiology and a whole pile of other biological differences, right down to the genetic level. Seems obvious, but many news stories about it seem to gloss over just how far a medical advance in mice is from anything resembling useful technology for humans.
Hell, if we could apply to humans all the therapies and treatments that have so far cured or at least helped with cancer, Parkinsons, dementia and aging itself in mice and rats, among other things, we'd long since have created a much easier time with these diseases.
Having spent some time working on aging research before transitioning to biotech, this paper genuinely excited me in a way that few studies have recently. The longevity field is littered with compounds that work beautifully in vitro but fail spectacularly in vivo - seeing psilocybin deliver both cellular lifespan extension AND improved survival in aged mice is remarkable.
What strikes me most is the mechanistic plausibility. The SIRT1 upregulation, reduced oxidative stress, and telomere preservation they observed align perfectly with what we know about successful aging interventions. When I was working on senescence research, we’d get compounds that would extend cellular lifespan by targeting one pathway, but they’d often have off-target effects that negated benefits in whole organisms.
The dosing strategy here is particularly clever - starting with 5mg/kg for acclimation, then monthly 15mg/kg treatments. That mirrors what we’re seeing in clinical trials for depression, but applied to aging. I remember being skeptical when colleagues first suggested psychedelics might have systemic anti-aging effects beyond their neurological benefits, but the serotonin receptor distribution throughout the body makes this increasingly plausible.
The survival curve (80% vs 50%) is the kind of effect size that gets my attention. In aging research, we’re usually thrilled with 10-20% lifespan extension. But starting treatment at 19 months (equivalent to 60-65 human years) makes this especially compelling - most aging interventions need to start early in life to be effective.
My main concern is the limited exploration of potential downsides. Delayed senescence can be a double-edged sword - those cells that keep proliferating longer might accumulate DNA damage that wasn’t detected in their short-term assays. We need much longer studies to understand cancer risk.
Still, given psilocybin’s remarkable safety profile and the FDA’s breakthrough therapy designation, this opens fascinating possibilities for combining psychedelic therapy with longevity medicine. Imagine treating both the psychological burden of aging and its biological mechanisms simultaneously.
One catch is both of those dosing levels are relatively large. This isn't toxic in the classic sense, but those are both heroic dosages on the mental effects side. I think this is like 20-80 grams of dried shrooms.
> The dosing strategy here is particularly clever - starting with 5mg/kg for acclimation, then monthly 15mg/kg treatments. That mirrors what we’re seeing in clinical trials for depression, but applied to aging.
15mg/kg seems like a lot, though. 15mg per person is a 'common' dose for a human. I don't know what the mapping between mice and humans is, but tripping on 1500mg of psilocybin once a month would be pretty taxing for me.
love this comment - i read this as well and was excited to see it on hackernews
I did tons of mushrooms in my twenties and mosr people estimate my age in my twenties. I am 35.
What a wild coincidence if true. Unless somehow the psychoactive effects are caused by the same thing... and how wild that would be considering the effect of the drug is to put you back into the state of in-the-moment wonder as if a child again!
Exercise, healthy diet, caloric restriction, adequate sleep, and stress management have also all had been shown to extend cellular lifespan and improve survival of aged mice - and humans.
Adding another thing to that list can't be bad can it?
Exactly, keep adding to it - and they all add up.
One sees many of these kinds of papers about X or Y doing this or that incredible feat of life extension in mice. The problem is that aside from many of these papers possibly having some dubious methodology, the subjects are mice. That's some seriously different physiology and a whole pile of other biological differences, right down to the genetic level. Seems obvious, but many news stories about it seem to gloss over just how far a medical advance in mice is from anything resembling useful technology for humans.
Hell, if we could apply to humans all the therapies and treatments that have so far cured or at least helped with cancer, Parkinsons, dementia and aging itself in mice and rats, among other things, we'd long since have created a much easier time with these diseases.