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.
> 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.
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.
These dosages are off the charts for what most people ever do.
A typical estimate is 15 mg psilocybin per gram of dried mushroom so for a 200 pound person that’s 90 grams of mushrooms. 5 grams is the classic heroic dose.
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.