#1

I have about a year and a half of Rapamycin left from my last order (I take 7mg once per week).

This week I’m going to buy another year and a half supply (which would give me a total of three years of Rapamycin), but I wouldn’t recommend that anyone order a larger supply than that.

Here’s why: we’re seeing some amazing advances in AI drug development, and there’s also a high likelihood that AI will soon be able to dramatically decrease the amount of time it takes to do trial tests for new drugs (speeding up FDA approval).

Long story short: I think that within the next three to five years, we’re all going to have access to new pharmaceuticals that will have a far greater effect on human aging and longevity than Rapamycin does.

I’m wrong more often than I’m right, but these are definitely exciting times we live in . . . what do you all think? Do you agree or disagree?

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#2

Sadly, I disagree - as Matt Kaeberlein said, the whole longevity field has stagnated. Despite the extremely concrete benefits, neither Matt nor anyone else can get even rapamycin to big trials in humans - it’s been an epic battle just to get it in dogs. The AI hype is just that - hype. Like all new technology, there is a lot of enthusiasm and unrealistic expectations, it’ll solve world hunger, cure cancer and give everyone a pony. How many times have we been through this hype cycle before? Every few years there’s a new one. Remember back in the 80’s the biotech bubble? I do. It was going to revolutionize medicine and yes, cure cancer. It fizzled ignominiously with just a few drugs to show for all the billions. Cancer is still bubbling along and even growing among ever younger people. Remember when the human genome was sequenced fully? We were going to cure every genetic disease under the sun. Gee, that one fizzled like a wet fart. Then an endless parade of stem cells (California invested billions), CRISPR, quantum computing, and on and on and on. Even AI has comically been popping up every twenty years or so since the 50’s. Look, true revolutions in medicine are rare. Drug discovery revolutions have been claimed literally dozens of times, and it’s still a long process. AI is just another fizzle in drug discovery. Oh, but it’s different this time! Sure, they always say that, otherwise you couldn’t spin up a new hype cycle.

Look, like all technology, AI has its place in medicine, especially diagnostics. But all the enthusiasts will be shocked by how modest the actual impact will be. It’s incremental progress, not the rare revolution.

I think you are quite safe ordering rapamycin for the next ten years at the very least, likely much longer.

And if anything, the FDA will be even slower with approvals.

New longevity drugs are in a timeframe of decades - from discovery to testing to approval to use. AI will make almost zero difference to speed up that process.

But hey your 3-5 years is short enough for all of us to witness, so if you’re right, we’ll see it soon enough, and you’ll be proven right - heck, I’m pulling for you! I dearly wish it were true! After all, I like everyone else is dying here, every day is a day closer to the grave. I’m highly motivated to have hope that miraculous drugs and treatments are just around the corner, but I also have my cold rational side, and this scenario just doesn’t pencil out based on my understanding of current reality. We’ll see, and soon!

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#3

Most likely any new longevity type drug will be unaffordable for 99% of the public, at least in the US, until it becomes generic.

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#4

I think you are correct that there will be new drugs identified with a larger impact than Rapamycin on longevity, but the issue will be that they will be priced much higher because they will still be “on patent”. So, while there will likely be better drugs on the market, the cost/benefit ratio will still favor rapamycin. If you have a lot of disposable income and can afford $10K to $16K per month for a drug (off-label use) then you will be fine. This is what the price of Everolimus was priced at until a few years ago, before it went off-patent. But any new drug approved in the next 5 years will likely be expensive for at least 7 to 10 years until it goes off-patent.

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#5

Certainly something to consider but I think the bio availability and the tissue distribution (ie crossing the BBB) will be the major advances over rapa. My own thought is that rapa is a potent, specific inhibitor of MTOR and it would be hard to improve on that aspect. There are already kinase inhibitors of MTORC1 but it isn’t clear to me that they are any better than taking more rapa. Their real advantage is that they readily cross the BBB.

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#6

I don’t try to focus on any specific mechanism, like crossing the BBB. I’m agnostic on mechanistic explanations for the simple reason, that the total system (human physiology) can often be unsolvably complex, i.e. there are more possible permutations than there are any physical computational capabilities (unsolvable mathematical equations). The only recourse under those conditions is the age old black box approach. We observe the input (f.ex. rapamycin) into the black box (body) and observe the output (f.ex. life extension in ITP trials). We can speculate about what happens inside the black box, and that’s great, that’s how we try to push science forward, providing ever more correct models, but that’s not dispositive. The only dispositive is the result, the output. If rapamycin extends life, that’s the key point, how it does that is very interesting but of secondary importance. Same with anything that improves upon rapamycin, say everolimus. I would run a head to head test, compare the two inputs rapamycin then everolimus and look at the output (outcome), if everolimus provides 10% greater LE compared to rapamycin, then that’s the superior compound. How it accomplishes that 10% LE premium, i.e. what happens inside the black box is a very interesting question worth investigating, but of secondary importance compared to the outcome.

So, if whatever is supposed to leapfrog rapamycin, say RapamycinExtra (RE), whether it crosses BBB or not, well, that’s of academic interest (and great interest at that), but I care about the outcome first and foremost. There are many drugs that don’t cross the BBB but affect the brain nonetheless, because they are metabolized in the gut (or liver or anywhere else), and those metabolites, not the drug itself affects the brain. So if I made up my mind ahead of time to look for a drug that crosses the BBB, I would miss the one that affects the brain even though it doesn’t cross the BBB. That’s why being agnostic about what happens inside the black box, and focusing on the outcome is of greater importance, at least in the immediate term.

I have no doubt that there are molecules that would work better for LE than rapamycin - and Matt Kaeberlein makes that argument very convincingly. That doesn’t mean we’ll turn one up anytime soon, and it will get FDA clearance and be affordable or that AI will be the deciding factor in any of this long chain from discovery to ending up with the average consumer. In fact, given the way the longevity space has been working so far, the regulatory environment and the economic incentive structure, I place my bet on the square that says “you ain’t seein’ nothin’ in the next 10 years, and certainly not 3-5 years”. YMMV.