Rapamycin: longevity benefits, surge in popularity, unanswered questions, and more

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#82

Sometimes you get side effects at first and they can be mitigated over time as your body acclimates (or builds resistance?) to Rapamycin.

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#83

Thank you for this. We did ramp up slowly and he takes long breaks after adverse effects but is reconsidering it again given new info on inflammation effects. We also take 1 whole grapefruit not the juice - is that still equivalent to 12 mg?

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#84

We are assuming that 1 whole grapefruit take prior to taking the rapamycin is the same as drinking the juice - and I think the measurements from @Agetron and perhaps others of blood / sirolimus levels suggest that yes, they are equivalent. But I have not seen any research studies on this, and it likely varies by type of grapefruit, etc. Perhaps read this thread for more info: Rapamycin and Grapefruit Juice

and What types of grapefruit juice increase Rapamycin levels the most?

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#85

Hello!!! I’m brand new here and seriously considering starting. I have so many questions, but this one was at the top of my list!!! The brilliant Sabatini knows as much, or more, than anyone on this topic, yet he isn’t motivated to take it,yet. This worries me!

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#86

Welcome to the forum.

If you have not already seen/reviewed

Review:

“Rapamycin for longevity: opinion article”

Rapamycin for longevity: opinion article - PMC.

“If you wait until you are ready, it is almost certainly too late.”

~Seth Godin

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#87

I hadn’t seen that, so thank you!

#88

If you watch the video above, Dr. Sabatini is waiting for some more data before starting Rapamycin. He’s still quite young, so he probably figures waiting a couple more years won’t hurt. He’s definitely a proponent of Rapamycin.

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#89

Thank you DeStrider! I did watch this and so did my doctor. When asking about it after learning Attia was on it a year or two ago, he said it’s too soon. But after watching the video, he gave me his blessing (although he won’t prescribe it :slight_smile: …. I did see he definitely thinks it’s great, but the waiting doesn’t make sense if he has no concerns… so it just made me wonder if he knows something I don’t know. I do get Matt and Peter are on it, so that probably answers that.

Because I’m new, I’m not sure if it’s best to ask my questions about it here, or should I start a new thread?

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#90

Beth - we are pretty free form here as far as questions and answers go. Feel free to post on this thread…

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#91

@RapAdmin Where do you “publish audio”?

#92

2 posts were split to a new topic: Rapamycin Questions from a New User

#93

Did anyone hear why Peter Attia switched his dosing protocol from 6 mg, 8 weeks on rapamycin and then 5 weeks off? What is he currently following for his dosing? Matt Kaeberlein, I recall, had an 8 week course for his frozen shoulder. Is he doing the 8 weeks on/5weeks off dosing regimen? What would be the optimal dosing regimen for a healthy male in his 70s?

#95

Thanks, Jonas. I’m glad to hear that the TRIAD study shows positive effects. As of January of this year, A&M University in Texas was still accepting dogs into their TRIAD study. The dose you mentioned caught my eye because my Doberman was accepted and began the REPAIR (DCM) Rapamycin study in February of this year. At the time of acceptance, he weighed 38.4kg and was prescribed 9.6mg per week which is 0.25mg/kg. He has been on that dose for 9 months now has experienced only positive effects.

That’s a considerable difference between the longevity dose and the REPAIR dose given, which they’re hoping will effectively work in tandem with Vetmedin for his occult DCM. In theory, the Rapamycin will keep his heart tissue healthy and the Vetmedin with help the heart efficiently contract. Vetmedin has a great track record for that purpose, but at some point when the ventricle becomes too flaccid, no amount of heart contracting is enough.

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#97

a critical distinction, yes

#98

dosage on AKG? feel anything?

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#99

Hey Jonas - I have had the privilege of having questions answered by Dr. Matt Kaeberlein through emails for almost 3-years. Maybe because I was an early participant to his rapamycin study. Had several contacts with him and his wife.

It actually was Matt that steered me to rapamycin.news (his perspective is cautious, unbiased and his recommendations solid).

Recently I messaged him about two things Arginine-alpha-ketoglutarate (AAKG ) and Calcium-alpha-ketoglutarate (Ca-AKG).

Also, what he thought about high doses of rapamycin. As some of you know from my own personal experiences and biological testing. I think about 6-8 mg is right weekly anything 12 mg or higher in my opinion is too much.

In the recent Peter Attia/ Matt Kaeberlein/ David Sabatini podcast on the News fed. “Rapamycin: longevity benefits surge in popularity, unanswered questions and more” I give you this.

When Peter asks David if he can think of any other molecules [like rapamycin] that spans from yeast - to flies- to worms- to mammals. David says other than dietary restriction he can’t think of a single treatment that has longevity benefits across species from yeast to mammals. Peter was not aware of any either - just rapamycin stands alone.
Matt says he is going to respectively tell them they are wrong. There are other things out there like alpha-ketoglutarate where there are reports of longevity in yeast and flies and worms and mice - it just hasn’t been tested as much.
For those of you that are Kaeberlein “Fan Club Groupies” like me here is his reply on CaAKG or AAKG.

mkaeberlin
"Sounds like you are doing great on your own personal healthspan journey - congrats!

Re: CaAKG vs. AAKG, I don’t know of any direct comparison to base a preference off of. And it’s important to keep in mind that the mouse longevity benefits of AKG are relatively small and have yet to be reproduced, so… we’ll see. Having said that, there’s probably little risk and some reason to believe CaAKG may have additional health benefits irrespective of targeting the biology of aging. Differences? CaAKG probably has some bone health benefits (at least for some folks) and calcium homeostasis properties you won’t get from AAKG. AAKG might be better at promoting muscle mass/recovery, although if you’re also eating a high protein diet I’d guess this is minimal. Assuming AKG is an active ingredient for longevity/healthspan, that piece should be the same for CaAKG and AAKG.

Next, I shared with Matt my dosing experience and biological markers.
When I did 6-8 mg weekly for 1 1/2 years, I had my best GlycanAge test and
TruMe test my biological age was 37 GlycanAge and 50 TruMe. I know
biomarkers are an iffy subject from your many chats with Peter. But, bare with
me. Numbers stayed consistent retesting at 4- months.

But, when I went high 36 mg rapamycin every 7-10 days. For 7 months… my biological age speeded up to 50 GlycanAge and 53 TruMe. Significant increase.

Going back to 6 - 8 mg rapamycin for 4 months my GlycanAge went back down to 47 years and after 4 more months down to 42 years… no inflammation.

mkaeberlein
Re: Rapamycin dose - I honestly don’t know. I understand Misha’s rationale for pushing it as high as possible until you get to side effects. My concern there is that you might be getting to side effects and not know it right away or at all (silent pathology) until it’s too late to reverse the damage. I have no evidence for that, but it’s a concern I have.

I absolutely think it’s possible that 36mg could be net detrimental to health while 6-8 mg could be beneficial. I am certain the optimal dose will be different for different people.

So there you go - a few more tidbits from the Rapa Rock Star Matt Kaeberlein.

Jonas - Sorry Matt does not address AKG dosage, but does think it has potential and needs more research.

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#100

Bryan Johnson included Ca-AKG in his protocol few months ago and takes 2x1000mg daily.

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#101

Great post, thanks @KarlT

Does anyone know their FKBP genetics? It would be interesting to see if anyone with a polymorphism for say FKBP51 is prone to side effects.
And say, a FKBP12 polymorphism is less prone to discernible benefits.

“Here, we identify the expression level of different FK506-binding proteins (FKBPs), primarily FKBP12 and FKBP51, as the key determinants for rapamycin-mediated inhibition of mTORC2. In support, enforced reduction of FKBP12 completely converts a cell line that is sensitive to mTORC2 inhibition to an insensitive cell line, and increased expression can enhance mTORC2 inhibition. Further reduction of FKBP12 in cell lines with already low FKBP12 levels completely blocks mTORC1 inhibition by rapamycin, indicating that relative FKBP12 levels are critical for both mTORC1 and mTORC2 inhibition, but at different levels. In contrast, reduction of FKBP51 renders cells more sensitive to mTORC2 inhibition. Our findings reveal that the expression of FKBP12 and FKBP51 is the rate limiting factor that determines the responsiveness of a cell line or tissue to rapamycin.”

#102