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Aging focused human trials of rapa analogues


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A company focused on aging research is conducting trails of a rapamycin analogue with a view to impact on aging in humans - although of course, they need a proxy of some kind, so they picked the immune system. Now, obviously, it's just one subsytem, but at least it is in humans, which should be interesting at least insofar as dosage and protocol are concerned, since we have no guidance in that respect except for the unacceptable original application in organ transplant rejection. Sorely lacking in detail, but here's a blurb:


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The first doubt which sprung out in my mind was why the immuen system. Joan mannick clarified that out in the linked interview, an aspect I did not know:


A: When you use it as an immune-­suppressive agent, it’s used at high doses. When we’re studying its effects on modulating immune function, we use much lower doses or intermittent dosing, and that’s where we see it actually enhances immune function.

The other interesting thing is, as we age the mTOR pathway becomes overactive in some tissues. So just turning mTOR down to “younger” levels rather than turning it off—which is what we try to do in transplant patients—may be of benefit in aging-related conditions.

The bottom line so appears to be:

  1. I fthe immune system is efficient (we don't get sick easily) then we're not candidates for taking that drug
  2. If we exercise some kind of dietary restriction and AMPK activating exercise (CR, Protein restriction, glucose control, aerobics) then mTOR by definition should not be overactive. Hence again we're not candidates for taking that drug
  3. If we like to indulge in any kind of foods then we might be candidates for that drug.
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Depending on what you're already aware of wrt rapamycin, I suggest taking a look at Dr.Alan Green's website;  In just a few minutes you can get an understanding of some of the 'basics':


He provides a very nice summary of rapamycin therapy which he offers as anti-aging treatment (with other drugs such as metformin as part of the 'Koschei Formula' - developed by Blagosklonny).  This is NOT a long read and Alan has really summarized this topic well imho - by the way - also imo one of the KEY things to understand and what even many medical professionals completely miss when discussing rapamycin is that, similar to 'the dose makes the poison'; in this case the 'frequency makes the poison'.

I.E. the elimination half life of rapamycin is stated on AG's website as 62hrs (+/- 16hrs).  Normally to suppress the immune system rapamycin is taken by organ recipients daily (this is repeatedly taken at 0.4x the half life); however AG's anti-aging approach as you will see (and that of Blagosklonny) is to take rapa at much longer intervals for example perhaps once per week - please read about this - I found it quite interesting.

The 2 other papers that I strongly recommend are:  (again these are not long or overly complicated)

"From Rapalogs to Anti-Aging Formula"  Mikhail V. Blagosklonny

"Koschei the Immortal and Anti-Aging Drugs"  MV Blagosklonny

I'd love to hear people's 'take' on this; I've been very tempted to actually go on the 'Koschei Formula' and contacted Dr.Alan Green howver in the end decided against it due to a few factors (essentially I'm not willing to 'tinker' with my meat suit with an entire suite of prescription drugs just yet since I'm still 44yrs old ... however I think I'd be willing to roll the dice if I was 25yrs older).




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Clinton, AG and his website has been discussed many times over the years, and so has Blagosklonny (the latter as long ago as 2011), just perform a search for Blagosklonny:


I don't remember which thread, but somewhere MR discussed the polypill of rapa, statin, bp, metformin a la Blagonsklonny and cited something to the effect that in mice/rats such a regimen resulted in a shortening of lifespan. It is a natural tendency to think that all interventions are additive and synergistic, but that is very often not the case at all, and when you are dealing with powerful drugs, it is never a good idea to just piggyback them. So too for diet - f.ex. apparently CR and rapa is a bad combination. Personally, I would ignore Blagosklonny without any human trials. The same goes for AG - the problem there is that he has run no trials and his dosing protocol seems based on nothing much. 

The entire value of the rapa analogue trial is in the fact that it's happening in humans and we get to see dosing protocols. That's huge. Now, it still won't tell us what the long term effects are on aging, but it's better than nothing - which is where we are at the moment with humans and rapa, we have very little data (other than in the context of organ transplant rejection).

Note too, that it's a rapa-analogue, probably because that way they can monetize it, as they don't own any rights to rapa. And unfortunately, all you'll be able to tell from this trial will apply specifically to that. I know it's natural to think that's the exact same thing as rapa, but it's not - often subtle differences in drugs make a big impact. So, in this context bringing in the musings from AG or Blagosklonny is not going to be very useful. In any case, you are only 44. I think you would be well advised to wait, you have the time - much better things should arrive within the next 20 years or so. The situation is much more grim for those of us who are older - we may not be able to afford to wait, and are forced to gamble blindly. 

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Matt Kaberlein gave a talk last Spring on rapomycin as an anti-aging drug at the annual conference on aging in the bio dept at UR.  (Dr. Kaeberlein was one of the speakers in one of the earlier CR Society meetings).  Prof. Kaeberlein claimed that the problematic side effect of rapa are greatly exaggerated, and that for healthy subjects, the side effects are minimal.  He believes in (eventually) using rapa as an anti-aging drug without modifications.  He is currently conducting a study using pet dogs and rapamycin.  He thinks it almost criminal that the FDA won't allow testing of the drug on critically suffering alzheimer's patients -- he claims that animal tests strongly suggest that rapa for extreme alzheimer's patients would be helpful.

I spoke with Prof. Kaeberlein after his talk.  I asked him if he thought that rapa and CR might work together well, or not.  He said that the too procedures have some common pathways, but that they also differ.  He then noted that it would be absolutely impossible to get approval to do such testing on people.

(But I bet you wouldn't need approval to make such tests on mice.  My opinion:  the main difference between a human and a rat is human arrogance. 😊.)

  --  Saul

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