Agreed… and the transcription - article says he’s stopped for now… that doesn’t sound like stopped forever.
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That argument - already optimized pathways - is an interesting one. It doesn’t mean that interventions to extend human lifespan don’t or can’t exist in principle. It just means that the pathways that result in shorter lifespans in animal models, such as rodents and species experiencing high predation, promoting early fecundity and reproduction, are optimized in humans. You might call them low hanging fruit. This would imply that those interventions that impact these “rodent” pathways may not work in humans, as that’s already taken care of by evolution. The same argument was also put forward wrt. CR. There may be something to that argument. But, I would not make a blanket statement wrt. ALL longevity interventions in humans, because not all of those map to rodents. There may - and certainly are - longevity pathways that can be impacted in humans. Otherwise we’d have to posit that humans are as longevity optimized as possible, which seems unlikely. There were simply no evolutionary pressures to make humans live longer, and we can try to fill in those gaps with interventions (drugs, but ultimately by design change through genetic engineering).
In any case, I think it’s entirely legitimate to ask if rapamycin buys humans anything at all, whether in healthspan or lifespan. I’m gambling that yes, because the pathway that rapamycin works on is such a fundamental one, and is preserved throughout the evolutionary tree. Unless you believe that humans reached an “all longevity pathways optimization” peak such that it’s impossible to improve upon - which I think is unlikely - then rapamycin has a good enough (for me) chance to work somewhat in humans. Humans are mammals. Are humans the peak longevity achievement for the mammalian physiology? No. There are whales that live longer. I don’t bring up non-mammals, such as sharks, fish, reptiles, mollusks etc. because the physiology is just too different. But 200 year old whales tell me that the mammalian physiology has inherent in it greater longevity capacity than the human 120-130. We can look at it from the whale point of view: “gee, rapamycin works in humans, because they have sloppy longevity pathways, but rapamycin will not work on us, because we, at 200+ year lifespans already have all pathways optimized, so fellow whales, we reject rapamycin as unlikely to work as it works in humans”. And here, I see my personal gamble on rapamycin as reasonable (for me and my risk tolerance).
Of course, it is also necessary to perform a cost/benefit analysis. There are costs to rapamycin that we know of: possibly lesser muscle hypertrophy, immune suppression, mouth sores, bacterial infection vulnerability and so on. Some of these might be mitigated through dosing protocols and polypharmacy. There are of course unknown risks. But on balance my risk tolerance results in a YES to rapamycin for me and my situation. YMMV.
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When you see surveys and studies, do you ever think to yourself, “Fu*k me, nobody ever asked me”?
As I have stated before, I don’t expect anyone who is healthy and young to feel any subjective benefits from taking rapamycin. Like an oil change for your car, you see zero immediate effect, but you know long-term, the motor will last longer if you do it.
The positive effects are more difficult to measure with routine lab checks; the negative effects are easier to measure, such as increases in lipids, glucose levels, etc.
So, has anyone published even an observational study of 75+ year olds taking weekly, medium-to-high doses for several years? I think not. Again, no one asked me (except members of the forum).
I felt immediate subjective benefits, such as a dramatic reduction in age-related pains, actinic keratosis, and essential tremors. Rapamycin has slowed down sarcopenia to the point that I am finding the progression too small to measure, as is any ocular degeneration.
Will rapamycin extend my life beyond my genetic programming fate? I don’t know, but I think it will. I am absolutely positive it extends median life spans and health spans.
Anyone who ignores the mammalian animal studies that almost universally show it extends life spans does so at their own peril. No one has presented any compelling evidence that humans are the exception.
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If Rapamycin works for yeast, flies, worms, crickets, mice, dogs, marmosets and humans (measures of health such as immune system and strength) with a 99% success rate over 164 studies, I think that’s enough proof for me.
The last bit of proof will come when @desertshores hits 150. That’ll cinch it for me. 
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Yes - I think the marmoset results confirm that the leap to primates for rapamycin is effective. So I’m pretty optimistic that we’ll get some benefits from rapamycin, though probably not the 30% we see in mice (at least with Rapamycin alone).
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I think it’s possible to get 15% if you pair Rapamycin with an SGLT2I/Acarbose/Metformin. For someone who would normally live to 95, that would take them to 110. That’s very respectable and reasonable.
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Good point. Pairing some drugs results in increased lifespan in animal models beyond the increase of each separately. That includes drugs that alone may not extend lifespan, such as metformin or simvastatin.
Frankly, with the drugs available presently for humans, I think polypharmacy is even more important than in animal models. And individualized precision medicine is especially important. At present, for me, it’s rapamycin, empagliflozin, telmisartan, pitavastatin, bempedoic acid + ezetimibe, and possibly pioglitazone in the near future (still doing literature research on that). Each of us has a unique profile of strengths and vulnerabilities, and addressing our individual weakest links should give us the greatest returns in health/lifespan.
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That’s what most, if not everymember of the forum, is doing. 
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I’m not trying to argue against Rapa, just saying there is a legitimate argument for not taking it. Everyone who gets positive benefits from Rapa is unfortunately just an n of 1. Medical treatment requires solid scientific studies.
Even if we agree that there is evidence that Rapa is beneficial, would it still be beneficial on top of maximizing all the other beneficial activities?
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Marmosets in captivity have a significantly longer lifespan than those in the wild. They get as much sleep and food as they need. Their food is probably nutritious, as I assume they are being fed vegetables instead of pizza, and a nutritionist probably plans their diet. Their stress levels are probably low (maybe too low?) They may even get blood tests regularly by a vet to measure for deficiencies, like normal zoo animals do. The only area where they may not achieve optimal results is exercise. Given all that, Rapamycin extends their lifespan 15% on a near-optimal lifestyle.
Now, let’s take your average American. Diet is crap. Stress is high. Not enough sleep. Obese. Not enough exercise. They rarely go to a doctor for prevention. If anything, Rapamycin would probably help humans more than your average marmoset who leads a pretty optimal lifestyle, IMHO. This is why your typical American dies at 77 and your typical wealthy American dies at 95. As for the rest of us here, we probably don’t live as optimal a lifestyle as the captive marmoset, so why wouldn’t Rapamycin help us? I’m betting it will.
I’d wager that a typical wealthy American on Rapamycin (plus SGLT2I/acarbose/Metformin) can gain an extra 14 years and live to 109 on average with the health of a 95-year-old. Here’s hoping I can celebrate my father’s 110th birthday with him.
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Didn’t the marmoset study also highlight negatives/failure of Rapamycin?
This is very similar to my current line of thinking! I feel like we should address the obvious (low hanging fruit), then look at maximising our natural lifespan through exercise, sleep, diet etc. That gets you into the 90+ bracket unless you’re unlucky. To get above that, you need something extra like the polypharmacy.
I made a post a few weeks ago about this idea (though it wasn’t well received). I used UK data, where a male lives to 78.6 on average. If we normalised 7 basic factors (smoking, hypertension, lipids, HBA1C, BMI, 150 mins exercise per week and cut alcohol) that number should be 87 years old. If you “optimised” them, the number should be 93.
Then you can think of pleiotropic effects of the drugs (like statins lowering inflammation, SGLT2i being neuroprotective etc). Maybe that pushes us past 100. And importantly, I am not aware of any significant negatives of weekly low-dose Rapamycin. So at the worst, perhaps it’s a waste of money.
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That’s the key…being on national TV and endorsing an immunsosuppressant like Rapamycin to prolong longevity could stir up not only huge controversies but also spell medico-legal issues from citizen, states and federal regulators besides creating public health nightmare.
Imagine individuals hearing about rapamycin and longevity on national TV, creating not only a black market but also consuming in a dangerously risky way jeopardizing their health!!
Imagine a month after the broadcast, ER reporting rapa toxicity, overdose, complications…and soon follow all kind of litigations and investigations!
I am certain his legal counsel advised him regarding how to precisely address the Rapa question.
As he has mentioned many times that there are lots of other things people should do before getting onto Rapa train specially cardiorespiratory fitness, zone 2 training etc.
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Some of you guys come up with the weirdest conspiracy theories where you question everyone’s motives. Attia is one of the realest ones there is. He gives his educated opinions and has never once made anything up as a result of some ulterior motive. Not everyone is an asshole like some of you guys think.
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I tend to agree, Attia generally seems to explain his changes when they are based on new evidence… Such as his changes on Keto and fasting. Until there is new information, I assume he was honest with the CBS interviewer.
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Peter Attia says he’s stopped taking Rapamycin because of mouth sores?
I’m guessing that most people don’t get Aphthous sores (canker sores) often, or at all, and if so, not severely because they would understand Peter Attia’s point. They hurt like hell and he’s already got four years of Rapa benefits.
For me, everything was reasonably ok for first year of using Rapa. However, I now get ulcers EVERY time I take any dose, thats about three years (four in total). My ulcers are large, wide-spread, painful and cause extreme discomfort for about two weeks. My teeth and gums are excellent bar a few minor fill ins. I’ve posted on this site my attempts to reduce the issues. My wife is a GP so I’ve tried almost every treatment.
I’m healthy, fit and don’t take any medications. I eat well, do HIIT training three times a week, live well and have great family and friends. I’ve schooled on the issue and I have mitigated the worst of the problems but I’m still constantly afflicted by the ulcers.
I suspect he’s just stopped to get a break.
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I assume you tried the Sabatini mouthwash protocol and it did not work? Based on mechanism of action I thought it should work in almost all cases, but if not, that’s bad luck. It all seems very unpredictable. I think RapAdmin got one when he just started, but then nothing since. I have not had one so far, but I’ve only been on rapa for less than a year and for the past three weeks escalated the dose from 6mg once a week to 10mg and will keep that up for another 2-3 weeks before going back to 6mg. I had my periodontist do a battery of tests on gum and bone health before getting on rapa and come November next week he’ll run the same tests to see if rapa has had any impact (this in the context of getting dental implants, so regarding rapa impact on bone regeneration, if any).