What Questions about Rapamycin do you have for Researchers?

[jimo3]

There seems to be a significant difference between the weekly & bi-weekly strategies. The 1st has a lower dose but keeps a consistent level each week & doesn’t wash out to the extent of the bi-weekly. The bi-weekly has a much larger dose initially but is offset by a much lower average in week 2, w/ a more significant washout at the end. Which strategy seems the best bet given our current understanding?

[AlexKChen]

Can rapamycin (at high enough doses) increase blood glucose spikes by inhibiting mTORC2? (I just had one lb of strawberries spike my glucose to 175 [and still counting…]) which, like, usually doesn’t happen [though i last had rapamycin almost a week ago). Maybe it’s the 2000mg of metformin I took…

Would rapamycin synergize well with SGLT inhibitors b/c of this? (b/c SGLT inhibitors bring down glucose spikes)

[shc]

Omg, I’d love if you could ask any of these questions:

(i) How do rapamycin and dietary protein (or lack thereof) interact with respect to
(a) prevention of sarcopenia
(b) protein synthesis ?
If rapamycin intake doesn’t affect protein synthesis, this means that mTOR is not necessary for protein synthesis? If not, what is the mechanism by which protein synthesis continues to takes place?

(ii) How exactly do fasting and rapamycin differ with respect to mTOR inhibition?
Does fasting /lack of protein inhibit mTOR more or does rapamycin? Any knowledge about tissue specificity for this (for e.g. effects on the brain)?

(iii) It’s known that there are immune benefits of rapamycin w.r.t vaccines and generated antibodies that can be observed a week or so after the dosage. BUT does taking rapamycin cause any immediate issues w.r.t immunity against viruses?

(iv) What is the impact of rapamycin on the effect of senolytics? For the best benefit, would one want to take these together or apart from each other?

(v) It is said that rapamycin reduces the body weight set point. By what mechanism does this happen?

[Boldi]

Are there any answers that go beyond intelligent guesses to the once per week vs once every two weeks at double the dose question?

[cronoslogical]

Which is the best test to take before beginning the rapamycin/metformin protocol? Do epigenetic clocks measure the effects of rapamycin/metformin?

[RapAdmin]

Regarding the bioclocks… this may be the best info anyone has - see the info from Prof. Morgan Levine:

Impressive BioAge Reductions with Rapamycin (anecdotal)

So far I’ve seen reports from 4 people who have seen significant benefits in terms of pre/post testing of biological age (reduction measured by epigenetic tests or Levine Phenotypic Age calculations) which, while still just anecdotal, reinforces the idea that rapamycin has some significant anti-aging effects in humans, just as it has had in every other organism its been tested in the past two decades. Following are the instances I have heard of, or members who have reported the results to me. Recently, a doctor who emailed me reports: I have been using rapamycin for several years and now opening my practice to local patients as well as telemedicine patients. My epigenetic test recently had me 18 years younger than my stated age (TruDiganostics) using the rapamycin. From our member @U…

[shc]

(vi) In the fasting literature, an extended fast and the subsequent refeeding can be considered to be different processes which when done right can be beneficial for longevity. Is there a similar analogue to “being on rapamycin” and the subsequent “ramping off of rapamycin”? Studies that show improved immune function immediately after having been on rapamycin suggests something similar could be at play. What implication does this way of thinking have for an optimal rapamycin dosing/schedule?

(vii) How do you optimize for rapamycin dosing during the pandemic? Rapamycin ON when the numbers around you are low, and Rapamycin OFF when you are in the middle of a wave?

[zmm]

@cronoslogical

nning the rapamycin/metformin pr

is there a protocol out there that mixes rapa and metformin?

[RapAdmin]

There is no “formal” protocol for mixing rapamycin and metformin as far as I’m aware.

I believe that many people mix the typical rapamycin anti-aging pulsed dosing protocol, and mix it with the TAME trail metformin dosing (the dosing protocol used in the large Metformin Anti-aging Trail that Nir Barzelai has spearheaded. Here is what I believe the TAME trial is using for metformin dosing (note - I don’t think the study has started yet, so things may change):

In the TAME study itself, the dose is listed as 850mg of Metformin 2 x per day, one morning, one night, this would equal 1700mg of Metformin in total per day.

TAME Design

• Double Blind Randomized Placebo Controlled Trial
• Dose: 850 mg 2x per day
• 18 Month Recruitment
• Range of Follow-up Times: 37-54 months (median 45 months)

Source PDF: Targeting Aging with Metformin: Design and Rationale, OAIC Annual Meeting April 19, 2016

[zmm]

there are different ways in theory to do this.

1. take metformin the first 72 hours after rapa, to “double up” the effect, and deal with any hyperglycemia side effects from the rapa
2. take metformin every day independent of rapa dosing
3. take metformin the 2nd half of the week (if doing weekly dosing) to cover the interval when rapa is at its lowest

any thoughts on the pros/cons of these approaches?

[shc]

Hi, when are you planning to send in these questions? Looking forward to your interview

[RapAdmin]

New results are due out from the NIA ITP program studies very soon… The acarbose and rapa study, etc.

I am in contact with the researchers and hope to interview them next month. But more generally i am just trying to get questions that i can pose as appropriate for different researchers i speak to going forward.

[shc]

Oh wow, I look forward to the new results. I feel like in some ways those results may also generalize to any (sglt2 or keto) + rapa

[RapAdmin]

Yes, it does seem that would probably be true given the key functions of both those drugs. I will discuss this with the researchers.

[RapAdmin]

Adding this question to my question list for rapamycin researchers. If you have other questions - please add them below in this thread…

Improve Bioavailability of Rapamycin (pt 2)

I’m not sure of this… I think people may talk about “higher levels” of rapamycin as a general term to cover higher levels of exposure to rapamycin, and not necessarily the absolute peak blood levels (cmax)… I’ll bounce this issue off Matt kaeberlein next time I talk to him and if anyone here is talking with Dr. Green or Blagosklonny in the next while, please ask them on their thoughts on this…

[shc]

What do we know about rapamycin’s half-life in different tissues?

[Maveric78]

@DrRoss

#3 Are the generic sirolimus manufacturers using the same nanocrystal technology that Pfizer uses in Rapamune?

I’m taking Rapamune… does this mean I require a lower dose than people on generics?

[KFISH]

What if any recommendations for adjusting dosage by body weight? 110Lbs Female vs. 180Lbs male?

[RapAdmin]

I’ve not seen any human research/clinical trials with rapamycin where they do the calculations of mg/kg for dosing. Instead its always simply a 5mg or 10mg dose. For example see these studies here.

If you want to do the calculations yourself - you may want to work from, and adjust for (based on biological differences… and I will ask the researchers about this also).

The dog rapamycin trials (TRIAD) at university of Washington is being done at .15 mg/kg in the dogs. Most people I’ve seen using it are in the range of .08 to .12 mg/kg dosing. I’m currently testing .19 to .25mg/kg (on more of a 10 day schedule or so). But I’ve been using rapamycin for 2.5 years now without issue - so I’m not the norm.

If you’re new to rapamycin, I think the safer option is to start low, start slow (e.g. 1mg/week and slowly increasing by 1mg/week), and then pause at a lower dose for a few months to see how you react, and do blood testing to check on key blood measures.

[KFISH]

Thank you! I will take it slow!