Any rapamycin questions to ask Matt Kaeberlein?

#41

Rapamycin definitely affects protein synthesis, including both basal and exercise-stimulated.

pharmacological inhibition or genetic ablation of crucial components of mTORC1 prevents overload-induced hypertrophy in rodents8-10, and the mTORC1 inhibitor rapamycin blunts the amino acid-induced increase in protein synthesis in humans.11, 12
https://onlinelibrary.wiley.com/doi/10.1002/jcsm.12505

Reference 12 is “Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis”

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#42

Ask him if he is on the same page as Dr. Blagosklonny when it comes to dosing.

I find this study somewhat disturbing. It seems there may be an optimal dose. In the study, the results of the lower dose were better than the higher doses
That begs the question: Is Dr. Blagosklonny’s opinion that the higher the better barring unwanted side effects?

“Our feline friends share 90% of homologous genes with us, with dogs it is 82%, 80% with cows, 69% with rats and 67% with mice”

Since we are more similar to cats than mice or rats, maybe we should rethink our dosing.

In addition, the cats in the study were just cats, not some special inbred strain.

https://www.triviumvet.com/insights/understanding-feline-hcm-prognosis-genetic-mutations-and-emerging-treatment-options-dr-joshua-stern-uc-davis

How much DNA do we share? | Average Percent DNA Shared Between Relatives | AlphaBiolabs USA.

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#43

Dr Blagosklonny is taking the same dose as Matt Kaeberlein is taking. The only difference today is that Matt cycles it.

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#44

First, if Kaeberlein is taking the same dose every two weeks and Blagosklonny is taking it weekly, it is not the same dosage any more than someone taking metformin 500mg once daily vs someone taking 500 mg twice daily is the same dosage. So no, they are not on the same page.

Blagosklonny originally touted on his Twitter feed that the highest dose without adverse side effects was the best dose.

However now in light of some other papers, this might not be the optimal dosage for humans.
I am still in search of the optimal dosage and in my case, “more”, definitely does not seem better.
That is why I am interested in Kimberlain’s research with dogs. As I posted earlier, dogs and cats share more genetic similarities to humans than rats and mice.

Since humans eventually mostly die from heart problems or cancer maybe we need to optimize the dose and not just take the maximum dose we can tolerate.

“Therefore, low-level rapamycin dosing most effectively controls tumors”

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#45

From the above table, they both are on 8 mg weekly.

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#46

What is the name of your podcast? I want to be able to find it on Spotify

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#47

Mikhail changed his dose from biweekly to weekly awhile ago so Matt Kaeberlein and Mikhail Blagosklonny is taking the same dose. Matt is just cycling with off and on periods also. Check the image I attached :pray:

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#48

You can search for Rapamycin Master Series. Here is an link to podcast in Spotify

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#49

If Rapamycin blocks mTOR complex 1, why adding Acarbose make the treatment even more effective? (What role does Acarbose play and is it independent from blocking mTOR or helping Rapamycin and how?)

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#50

FWIW

That question should be asked to the person that was the lead researcher on the experiment/paper published.

I think that was Richard Miller?

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#51

I’ve heard it boosts mtor complex 2, so if Rapa pulls down 2 a bit, then maybe acarbose helps boost it back up?

It helps starch make it through the gut to the colon where it can be made into short chain fatty acids. These are thought to be good. Also this helps reduce long term blood sugar. And SCFA also activate GLP-1, we learned recently, so that could help control blood sugar too.

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#52

Are there any health conditions in senior dogs that would preclude them from taking Rapamycin? For example, kidney and liver disease are common in senior dogs, so would Rapamycin help or harm senior dogs with those diseases? Are there any dosing updates that would replace the .1mg/kg MWF dosing schedule?

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#53

Please ask if using rapa has downsides for folks with osteoarthritis, based on this study with guinea pigs that made arthritis worse, along with raising glucose - though dosing was continuous, not weekly. Rapamycin-induced hyperglycemia is associated with exacerbated age-related osteoarthritis - PMC

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#54

This article about blood pressure med rilmenidine, showing it’s an alternate way to inhibit mTOR, has gotten a lot of attention for possible lifespan extension, any comment from Matt? Will it be evaluated via the ITP study with mice? https://onlinelibrary.wiley.com/doi/10.1111/acel.13774

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#55

What would be the 42ppm dose done in mice with 26% lifespan extension in dogs/humans?

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#56

Yes: please ask this! And so he doesn’t have to answer it off the cuff, please send him the paper in advance, and to head off what may be his off-the-cuff response, please point out that while there are previous studies that found rapa or genetic mTOR inhibition to be protective against surgically-induced OA in young mice, this is the first study in primary, age-related OA.

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#57

See this handy if depressing table from our intrepid administrator:

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#58

I had the interview with Matt this Thursday and we talked around 2,5 hours and I needed to cut out lot of questions also otherwise it would have been 5 hours :sweat_smile: But we will do a second interview in the future. So just add more potential questions here in this discussion thread and I will take a look next time which has been covered and not :pray:

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#59

Fantastic! We are eagerly awaiting your podcast.

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#60

Did you get the osteoarthritis question in?

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