Starting Rapamycin Antiaging Human Trials

Rapamycin has been proven to extend the lifespan of mice, warms and yeast. is starting a large clinical trial named Participatory Evaluation (of) Aging (with) Rapamycin (for) Longevity Study, or PEARL, to see if the antiaging effects of Rapamycin apply to humans. This will be the first study to see if Rapamycin works as well in humans as it does in mice.

The PEARL trial will follow up to 200 participants over 12 months testing four different Rapamycin dosing regimens. It will be double-blind, randomized, placebo-controlled and registered with The principal investigator is Dr. James P Watson at UCLA, who was also a PI for the famous TRIIM trial.

Tests and measurements will be taken, both after 6 and 12 months. These will include autonomic health tests, blood tests, body composition tests, fecal microbiome testing, immune and inflammation health tests, methylation age clock testing and skeletal muscle tests.

A study from 2019 shows that while Rapamycin is somewhat similar to calorie restriction it has different effects in other ways.

The current data show that dietary restriction and rapamycin have different effects on many pathways and molecular processes. In addition, these interventions affect the lifespan of many genetically manipulated mouse models differently. In other words, while dietary restriction and rapamycin may have similar effects on some pathways and processes; overall, they affect many pathways/processes quite differently. Therefore, rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone.

Mikhail V. Blagosklonny wrote Rapamycin for longevity: opinion article in Aging Journal.

He said the following about rapamycin:
If used properly, rapamycin is not much more dangerous than ordinary aspirin. Aspirin, one of the most widely used nonprescription medications, may cause numerous side effects, including life threatening gastric bleeding. The manufacturer lists as possible side effects: ringing in ears, confusion, hallucinations, seizure, severe nausea, vomiting, bloody stools, coughing up blood, fever and swelling. Still, millions of people take aspirin daily to prevent cardiovascular disease and cancer. It was calculated that the benefits of aspirin are greater than their risks. I believe the benefits of the anti-aging effects of rapamycin/everolimus may even be greater.

Rapamycin known in the clinic as Rapamune or Sirolimus, was unlucky from the start, however. Twenty years ago, it was labeled an immunosuppressant and used to treat renal transplant patients. If rapamycin had been labeled an immunomodulator and anti-inflammatory drug instead, it would sound much more appealing now. At anti-aging doses, rapamycin “eliminates hyperimmunity rather than suppresses immunity” or, more figuratively, it “rejuvenates immunity”. This enables rapamycin and everolimus, a rapamycin analog, to act as immunostimulators, improving immunity in cancer patients and the elderly. For example, rapamycin reduces the risk of CMV infection in organ transplant patients, improves antipathogen and anticancer immunity in mice, prolongs lifespan in infection-prone mice and protects aged mice against pneumonia. Rapamycin also inhibits viral replication. As a noteworthy example, rapamycin inhibits replication of the 1918 flu virus (the deadliest flu virus in history) by 100-fold, and also protects against lethal infection with influenza virus when administered during vaccination. Still, as Dr. Allan Green advises, patients taking rapamycin should be carefully monitored for skin and subcutaneous bacterial infections, which should be treated with antibiotics.

Rapamycin and everolimus are FDA-approved drugs, safe for human use. Since 1999, rapamycin has been used by millions of patients with no unexpected problems. One may suggest that rapamycin/everolimus are safe enough for very sick patients, not for healthy people.

Rapamycin reduces the risk of cancer and can extend the lives of short-lived animals by 7-14%.

There is a separate antiaging trial from the TAME trial for the antiaging effects of Metformin.

SOURCES –, Aging journal, Afar
Written By Brian Wang,

29 thoughts on “ Starting Rapamycin Antiaging Human Trials”

  1. If you use enough elderly people, the fraction that would naturally die in a year should be high enough to see if it has any effect. Assuming it does not have its main effects in middle age or younger.

  2. Well, the first given, right off the bat, almost day 1, would likely be a stock market collapse to beggar anything in history.

    The market is a delicate thing and even the knowledge that they weren't doomed to slowly die of old age would change peoples' work ethics, spending patterns, and investments, pretty much over night, hammering out some of the tent poles the market is suspended from.

    Long term it would recover, and then some, probably, as people saw the advantage of long-term planning and saving when they themselves would be around for the long term. But some people would be like, "Hey, I don't need to save for retirement anymore cuz I can always work." Income inequality might escalate enormously.

    Consider life insurance. This would kill "whole life" (small loss) but what would people do about life insurance? Buy more, because a life that is potentially centuries long is worth more? Or just stop buying it altogether?

    A lot of folks might suddenly quit their jobs to restart a new career (for many reasons), or dump their spouse (for many reasons), when they might not otherwise have done so.

    Assuming there are no limiting factors associated with the mind or personality, I worked out that a population of people that didn't die from old age would have a half-life of about a thousand years. That's assuming also, that suicide (and a huge surge in extreme sports) don't take a huge toll of those that fail to find purpose in their long lives.

  3. I concur with doomarz: By its very nature, abolishing aging would not abruptly change things. Though the changes would eventually be vast and cumulative.

  4. One thing to consider is that once there is no more aging all the changes might be happening slowly ,over many decades , and still be perceived as blazingly fast after the fact.

    Another thing to consider that there will be many "futuristic" changes happening simultaneously you will heat something called a "prediction wall".

    But for the book's sake, you can consider an otherwise technologically stagnant society on our current level but with the rejuvenation pill. if it was at medieval level after a few hundred years you will get something very close to the elves. Similar paradoxical morality and thinking…

  5. In some ways, but the main thing that makes lifespans in the past look so bad was that the chance of making it to 20 was pretty much even odds a lot of the time and childbirth (and its complications) killed around 15% to 20% of the women. Granted, in the British Isles in medieval times, it looks as if most adults died before 50 and only a very few made it to 60, but this wasn't an especially healthy area of the world to live in without knowledge of what a healthy diet is (and access to one), central heating, and an understanding of germs.

    Other parts of the world fared better, and there were at least some people that lived to what even we would consider to be a ripe old age, so the example was there. We don't have anyone living past a century who remains relatively "active" in world affairs, and certainly not to 150 or more.

    For years I played with writing a novel where a major pharma suddenly produces a relatively affordable pill that permits indefinite lifespans. The first half is easy. Some entrenched interests trying to suppress it and preserve the status quo, some wanting to control it for power, some wanting to keep it for themselves but deny it to the masses, others deciding (for all of us, as many people are wont to do) that we are better off without it.

    But then it gets out and that's where I simply cannot fathom what would come next, except a lot of change, to put it mildly.

  6. I agree. But I also want to say that there are some serious flaws in SENS too. The recent work with partial cellular reprogramming suggests it is wrong about epigenetic alterations being a consequence and not a cause of aging. Regards this particular trial and based on hallmarks of aging, I am leaning towards healthspan over any huge lifespan increase in humans.

  7. I agree, the research is worth doing. But based on the theory I wouldn't get my hopes up. If the approach does work it points us towards a much more optimistic theory of aging than even what Aubrey puts forward.

  8. Right, but the original comment was not directed at you. Also as I said elsewhere, these people are not biohackers they are Ph.Ds and M.Ds following scientific method. This isn't a case of Fred in the shed and his biohacking mates.

  9. The people doing this are not "biohackers" Otto, they have a Ph.D. and an M.D. No one has said a word about circumventing the system and given they are following FDA clinical trial process, it strongly suggests otherwise. James Watson, Ph.D. and Sajad Zalzala, M.D. are organising the trial and have the experience. Did you like, even read the PEARL page?

  10. It's a little bit more complex than simply being a calorie restriction memetic. Also, the point about this to find out if the results do or do not translate to humans, which has never been tested. If they do not then you can consider this further validation of SENS, if they do then you will have to re-evaluate SENS as an approach. Either way it's interesting and will help the field regardless of the result.

  11. Short lived animals have evolved to live much longer in response to dietary restriction because short term famines can mean the difference between passing on their genes and dying without leaving offspring. There is no reason to believe the same thing about long lived animals which can simply delay breeding for a few years until the lean times are over. Studies bear this out, the longer the lifespan of an animal the less impact of dietary restriction on longevity. Read Aubrey de Gray's book, it goes over all of this stuff.

  12. Alchemists have discovered a lot of useful stuff. Albeit, not the ones they were looking for

  13. for this treatment yes. For longer terms there might be some loopholes. There was some research indicating that rapamycin insulin sensivity might not be such an issue and rather an artifact of how blood glucose is measured. Anyway it can be controlled with diet (CR) and metformin.

  14. Since rapamycin is in use for some 20 years such side effects should have been detected. I tend to think as rapamycin as more or less calorie restriction mimetic, so don't expect huge increase in longevity. Probably can lead to nice health benefits in some groups…

  15. Compared to the average life expectancy only 200 years ago most of us here are quite old farts… If a woman got married much after 18 she was considered a spinster, for example. So we kinda have a clear idea on what to extrapolate and what would be the changes to the society if /when the anti-aging actually takes off.

  16. This part is especially interesting:

    "…rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone."

    As well as:

    "If used properly, rapamycin is not much more dangerous than ordinary aspirin." 

    This whole life extension thing is something that should have received Manhattan Project levels of support starting decades ago. So many potent possibilities; buy us another 50 years and see what we can't do with it.

    Future generations are going to marvel that we had children, achieved whatever we were going to achieve (not necessarily in that order), and died while we still children ourselves.

  17. The fact is, as any experimental biologist will tell you, there is such a huge amount of systemic cross-talk and non-specific effects, that a significant amount of control experiments and due diligence have to be done. This is why we have peer review. Even so, false positives are accidently published and harm occurs to experimental subjects (both human and animal). Biohackers like to portray scientists as gatekeeping and gaslighting them – we are not. Biology is easy to understand. To manipulate it and get accurate results takes years of acquired skill. All a biohacker is trying to do is circumvent all this, and as any 1st year Ph.D student will tell you, this will not ultimately work as science doesn't care about your trendy new designation. This is why biohacking will never be the exciting prospect it appears to be, at least until real scientists have done the ground work for them. Or of course in isolated instances, they have some remarkable good luck.

  18. So what about the diabetics? Is there a solution to that angle, or are they just ineligible for this treatment?

  19. I completely agree, and as someone who has published several papers on the matter, I'm not sitting on the sidelines and scoffing.

  20. This seems odd to me. I spent years researching mTOR (mammalian Target Of Rapamycin), using rapamycin and its synthetic analogues such as RAD001. mTor is a signalling protein that regulates protein synthesis (i.e. translation of mRNA). Turning down protein synthesis will doubtless slow metabolism down, and I'm presuming this is why it prolongs life in rodents, but what other effects will it have? Whatever they are they are likely to be slow to emerge, and possibly permanent.
    What if you turn down the expression of an essential heart protein to a level that causes atrophy for example? If you turn off protein synthesis altogether, you rapidly die. It's the interpretation of your genetic code itself, and couldn't be more fundamental to life. This is a dangerous thing to play with.

  21. Well at least they are out there trying to understand it through experiments. Easy to sit on the sidelines and scoff.

  22. There are biomarkers that can tell you if you're doing something that may lead to a longer life. Or you can take the TAME trial route and see if the treatment delays the onset of a number of diseases of old age compared to non-treated. Or, and while that's not the case with Rapamycin, you can just look at the patients and if they look and feel younger, you don't have to wait decades to see that they will live longer; I suspect that this is what will happen with TRIIM X.

  23. I'd like to volunteer for such a trial, but apparently I'm still a couple years too young.

    First time in a LONG while I've been too young for something…

  24. If you are testing longevity surely the timescale for the trial should be more than 12 months.

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