Separate Antiaging Trials for Rapamycin and Metformin

AgelessRx claims that PEARL is the first nationwide telemedicine trial and one of the first large-scale intervention trials on Longevity. The human trial is a stepping stone to the way to bringing rapamycin to the Longevity market. PEARL (Participatory Evaluation of Aging with Rapamycin for Longevity) is a $600,000 trial with the University of California. They will evaluate the safety and effectiveness of rapamycin in 200 healthy adults for Longevity in double-blind, randomized, placebo-controlled trial.

Interested patients will be screened for eligibility using telemedicine. Eligible patients include those aged 50-85 of any sex, any ethnicity, in relatively good health, with only well-managed, clinically stable chronic diseases.

TAME is a separate $75 million trial to clinically evaluate Metformin drugs for Longevity properties. TAME has a composite primary endpoint – of stroke, heart failure, dementia, myocardial infarction, cancer and death. Rather than attempting to cure one endpoint, it will look to delay the onset of any endpoint, extending the years in which subjects remain in good health – their healthspan. A $40 million donation has been combined with a $35 million NIH grant to fund the TAME trial.

AgelessRx is a platform that sells drugs and supplements including metformin and NAD+.

SOURCES –, AgelessRx
Written By Brian Wang,

15 thoughts on “Separate Antiaging Trials for Rapamycin and Metformin”

  1. Recent paper on hyperbaric oxygen therapy resulting in telomere elongation & reduction in cellular senescence. Messing around with telomere lengths without improvements in age depressed repair mechanisms could yield undesirable results.

    DOI: 10.18632/aging.202188

  2. Yes, this is interesting. As telomere length is enzyme-mediated, perhaps this will render a clue as to what signalling pathways need to be targeted as I guess most people can't afford the installation of a hyperbaric chamber, and they are not good for your health unless you have decompression sickness or MS.

    The irony here is that an increased ppO2 environment causes DNA damage through ROS, and one of the key causes of ageing is DNA damage….. So you get more cell divisions vis increased telomere length, but with accelerated ageing through DNA damage. In effect, creating a race of theoretically immortal yet cancerous prunes.

    This technique does not come without risks either – any scuba diver will tell you about the oxygen toxicity risks to your nervous system of increasing your ppO2 to anything but mildly above pressure at sea-level.

    There must be some biochemistry here – now we can stimulate it with O2 it we can start to find out how to stimulate it with other safer means.

  3. The elephant in the room is that the existing FDA 'process', the 'real' interest' with the public, and the availability of research funding/ staff simply does not support a strong anti-ageing intervention program. The FDA is in the business of prioritizing sickness relief under traditional definitions of illness and its database of pathologies. People, in general, do not want to die, but neither do they want to work too hard to live an extended time – if they did, exercise, healthy eating, and various fasting/ lifestyle choices would be huge. The number of fast-food restaurants/ bars -to- gyms/ supplement stores/ fitness-priority retail ratio is a many-many-score -to- one. Meanwhile, the cosmetic surgery industry continues to thrive (especially under reduced regulations). Further, the means of incentivizing and researching anti-ageing is way out of touch with other types of investigations. Grads don't go into geriatrics/ gerontology. These kind of programs are rare at College medical facilities. Olds don't dump money into long-term remedies – they barely even contribute to cryogenics – the only real and current 'Hail Mary' of longevity. The bottom line is that it is only a passionate few that carry the torch for such a future – though some are billionaires, to be sure. My guess is that the first serious trials, testing, therapies, and regular appointments will be offshore and medical-tourism. Also, self-testing. Whatever happened to those research hub sea-steading islands?

  4. The most that can probably be expected from it is that it has the same effect on healthspan/lifespan as excercise.

    That's a huge amount of benefit. Especially on healthspan. Exercise-in-a-pill would get vast amounts of attention from consumers.

  5. You will see the best results in people that have some kind of metabolic unbalances and with prolongued use of this medicine. Billions are being put into this and the way it will sell is by marketing not merit of the product. A bit like hair falling products and skin care expensive treatment, only that this time you can't observe directly the results at least in a resonable time frame. Again, this products will sell well, it's just you could get better effects if you are well informed and willing to change and you actualy would save thousands of dollars compared to the use of this produts or nothing at all.

  6. Indeed. And I have often wondered what the negative aspects of chronic inhibition of Raptor-dependent protein synthesis via mTOR were, you'd imagine there would be some.

    The key to anti-aging technologies lie in DNA damage prevention and repair and safe non-oncogenic telomere polymerisation. CRISPR is in it's infancy, we should look there rather than archaic chemotherapy agents.

  7. Yeah if metformin turned out to work well then it would be a gain. But the problem is that it is actually a poor candidate for a longevity drug. The most that can probably be expected from it is that it has the same effect on healthspan/lifespan as excercise. By that measure other existing drugs like statins that lower blood cholesterol are also longevity drugs.

    Is the potential value of the TAME study zero? No. But imagine if 40-80 million had instead been spent on trialling a protac senolytic drug, or on Oisin Biotechnologies' P16 suicide gene therapy? Those could turn out to produce actual significant gains which would get the attention of consumers.

  8. I think it would do the exact opposite of sucking away funding from damage removal treatments that could have a large impacy on healthspan and lifespan

    These (if successful) could be the easy, straightforward, beginner products that open the entire field up to being taken seriously by researchers, financiers, consumers and regulators.

    You rarely jump in with the most desirable, advanced, radical product in a brand new field.

  9. My understanding is that Metformin only really works to suppress appetite when it comes to anti-aging. I would be much more interested in finding a solution to turn back the biological clock, to really reverse the damage to DNA that has been done. There are so many factors related to aging.

  10. The real problem is these interventions will almost certainly do less than exercise, in isolation they are not a bad thing, but they are sucking away funding from damage removal treatments that could have a large impace on healthspan and lifespan e.g. senescent cell removal, glucosepane removal, lysosomal garbage removal. Of course the degree to which funding for a metformin trial could be redeployed to another trial is up for debate, and is certainly not 100%, but I don't think it is 0% either.

    The one good thing of the TAME metformin trial is that it has forced the hand of the FDA to allow a trial targeting a mixed composite endpoint that is "aging" and not a disease of aging. 80 million to buy that might turn out to be a bargain (although in a better world no one should have to pay the FDA consultants for this privilage).

  11. Metformin has a rather mild effect and after about 2g daily dose the effect doesn't increase. Still benefits outweight the side effects. There levels tens of millions people using it right now. Rapamycin on the other hand is much stronger and by definition MTOR altering (r in MTOR stand rapamycin). Metformin might give a few extra months of health span if taken by the whole population. Summer individual reactions might be a net loss, though.
    Rapamycin is more potent and more dangerous. If used right after say 45-55 might squeeze a couple of extra years of health span. Nothing to sneeze at, but far from a Miracle

  12. perhaps, but the point is that all the 50+ yr-olds in 2030 (like me) will want their cellular structure/ organs as intact as possible so the first selection of 5 of the 7 recognized SENS solutions (by then) will be working on a viable subject, not a highly damaged senscent cell ravaged 'near-corpse'. Its all about life span solution 'trajectory' and keeping ourselves as healthy (minimally-damaged) as can be maintained as these interventions are improved and optimized over time.

  13. Both are calorie restriction/stress response, so neither will likely do much for lifespan beyond what can be achieved with exercise:

    Real rejuvenation therapies are ones that remove the underlying damage that is aging, not ones that try to make an aged metabolism altered by this damage work better (a losing strategy as the damage is still building up e.g. L dopa and Parkinson’s).

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