The National Institute on Aging ITP study on Cohort 2017 is completed and results will be published soon. I’m curious what you think the results will be for Rapamycin + Acarbose combined treatment in mice. Please vote on the poll below. What do you think results will be and why.
In the Cohort 2017 study they are testing Rapamycin/Acarbose at 14 ppm/1000 ppm, starting at 9 and 16 months.
Rapamycin by itself (in the Cohort 3, 2006 study) when tested at 14ppm, and when started at 9 months resulted in 13% increase in median LS for males, and 17% Median LS increase for females.
Acarbose by itself, when dosed at 1000ppm starting at 16 months, for male mice treated with ACA, there was a 6% increase in median lifespan and a significant 12% increase in maximal lifespan. ACA started at this late age had only a small effect on median lifespan in females, but led to a significant (6%) increase in maximal lifespan.
So, what is your bet on what happens when Rapamycin and Acarbose is combined?
Multiplicative Results - Higher than just adding the discrete RAP and ACA median LS increase
Additive Results - Just the same as adding RAP and ACA discrete results
Neutralizing Results - RAP and ACA Drugs cancel each other out, so no increase in median LS.
Negative Results - Shorter Median lifespans than Typical
0voters
Post your rationale on why you believe this, and with an exact percent change in median lifespan and we’ll give “longevity bonus points” for people who come closes to the actual results when they are announced.
The past RAPA and ACA ITP studies have been daily dosing. Not sure what the exact diet the mice are fed - but if its the same baseline diet for all the studies (which I would assume would be the case) - and the only variable is the drugs they are taking - why do you think the that the macro composition would matter?
Moderate/High starchy carbs => multiplicative results because acarbose can help much more here with reducing glucose or insulin spikes (and also reduce the subsequent activation of mTOR via AMPK) especially when rapamycin is also causing some insulin resistance. Higher the starchy carbs, more obvious would the multiplicative effects be. The result one way or the other would be like having keto + rapa together.
Low carbs => Acarbose essentially won’t make a difference
That covers probably two of the options. I highly doubt that we’ll see neutralizing results or negative results
My guess is “less than additive.” Both rapa and acarb have anti-inflammatory effects, though through different mechanisms. However, the effects may be overlapping and not additive. My guesstimate on % change in median: male 17%, female 17%.
My theory is that the mechanism of action for rapamycin and acarbose is largely discrete and different from each other - so they are likely to be additive, but then there are likely some small level of overlap of some of the effects e.g. perhaps some of the MTORC2 effects overlap with some of the acarbose effects - so that the net effect will be slightly lower than if they were completely independent. In fact, I suspect that the degree to which the two are not additive indicates the level of overlap of the two drugs in terms of pathway impacts.
If they were completely independent pathways then I think it would be purely additive - so Median LS for males would increase by 13% (rapa) and 6% (Aca) for a total of 19% increase in median LS. But - if its lower than 19% (say 15%) - then that the 4% reduction from the purely additive result represents the “overlap” of the two medications’ pathways.
For example - here is a new paper that suggests overlap in mechanisms and pathways:
Isn’t there a 5th option, ‘adding Acarbose to Rapamycin doesn’t increase lifespan beyond Rapamycin alone’?
This would be my vote and was the case with Metformin. I think, once you’ve decreased inflammation beyond a certain level, decreasing it further won’t increase benefits.
OK - it looks like the results are in (paper still not published yet - but its been in the works for months I know) - Rich Miller announced the best results they have ever had in the ITP program.
Starting at 9 month of age with rapamycin and acarbose (I don’t know yet the doses yet) resulted in 29% increase in lifespan in mice.
It is shocking after all these months and years that we all scrutinize published test results and find that long held public believe in supplements such as Spermidine, curcumin, green tea and now Fisetin are absolutely no help whatsoever! I took all of those and I’m sure most of us did! I find it nauseating and sickening that the public is constantly being duped by these so-called “legit” published review sites! It looks like ITP is the only thing you can count on now. I only discovered ITP and their methods in recent months through Brad Stanfield’s videos.
I agree with you that almost all studies that show significant positive effects from intake of various substances or approaches to eating turn out to be greatly exaggerated or totally false. In most cases though, I don’t think it is due to deliberate attempts to defraud. I am just as frustrated nonetheless. Actually, I find some people in the longevity community to be pretty much the only decent sources of some actually utilizable information.
