#21

Thats a really helpful question because i dont know the answer and it made me do a search and i found this paper

I need to read up on this.

The reason for 3 weeks is that i normally want mTOR not to be inhibited

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#22

I would be careful here, don’t conflate aphthous stomatitis which can be auto-immune and respond well to topical steroids with ulcers induced by rapamycin which might be due to interruption of rapid cell division (via m-TOR inhibition) in the mucus membrane. Steroids can worsen the latter as it interferes with healing and repair.

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#23

There is uncertainty as to how frequently mitochondria replicate. There are figures between 2 and 350 days. Rapamycin is used to remove mitochondria so that mitochondria replicate and hence is intended to reduce the half life.

I use a number of interventions to increase mitophagy. The reason I set Rapamcyin at 21 days is because it has a relatively long half life. Hence it has a major effect for a few days and then the effect reduces gradually. Basically I don’t want it having an effect on my metabolism for more than half the time. I have for now set this as an accelerated 6mg every 3 weeks.

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#24

Thanks. I was surprised to learn just how short was the half-life of mitochondria (as they used to be bacteria I shouldn’t have been too surprised). For simplicity I think of the “replacement” process as two steps: (1) elimination and (2) rebuild and growth.

The elimination comes of damage (age of Mito, usage of Mito, availability of antioxidant protection) and shortage of energy and need for substrate. Time in life exposed to ROS, yeah OKRapa, fasting, endurance exercise, protein restriction

Rebuild and growth comes from refeed after rapa or fasting (energy & substrate shortage) and stimulus (endurance exercise for Mito).

So I’m thinking of timeframes for each….enough time for a need for mitophagy, then enough time to recover from increased mitophagy. Similar to you, I also want the rapa to clear out to zero before I get another hit. I use a 2 week cycle but take an extra week off every 5th week to be sure.

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#25
  1. Will we have data from Wormbot experiments publicly? (I mean all data or at least the best hits) (beyond community-sponsored only as we have now)
  2. What would be the direct dose of Rapamycin from mice to humans translating it from NIA ITP studies? (14 ppm or 42 ppm to human)
  3. Do we have any lifespan difference from Rapamycin in Dog Aging Project? When we will know results of Dog Aging Project study?
  4. Do we have any lifespan benefits of Rapamycin in monkeys?
  5. What would be his 2nd best “lifespan drug” based on studies(beyond exercise, sleep, etc)?
  6. What was the longest lived worm in Wormbot?
  7. He said once “if mice don’t live 900 days, it may not work”, do we have similar threshold for C Elegans and fruit flies?
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#26

This is an interesting question, and perhaps others here have already researched it, but to what degree or level does rapamycin induce mitophagy? The boost in autophagy with rapamycin is well-known and document, but I’ve not come into much literature on rapamycin and mitophagy. Of course I haven’t looked much on this specific issue either.

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#27

I am sort of assuming that the prime effective subset of autophagy that achieves the positive results from rapamycin is mitophagy.

https://www.embopress.org/doi/full/10.15252/emmm.201708799

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#28

This may be particularly helpful

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#29

In MDPI MDPI - Wikipedia
Looks like a mechanistic study, the human body is more complicated then what you can figure out in such a way.

#30

From your paper…

“Mitochondrial impairment, which roughly occurs in half of the organelles, is shown to be related to mTOR overexpression and autophagy suppression”

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#31

Thanks, but in the end mitophagy is a subset of autophagy.

#32

Should you lower Protein levels on the Rapamycin day, if you consume a high protein diet?
Will the high protein minimise the effects of Rapamycin?

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#33

That’s good, however I would ask should you lower protein in general or just BCAA’s especially leucine which is a very potent m-tor activator.

Will the high protein minimise the effects of Rapamycin?

Will the high protein minimize the effects of Rapamycin? If potentially so, should rapamycin and high protein (esp. BCAA) be staggered as opposed to stacked ?

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#34

Hi, I participated in your study.
I have osteoporosis and I want to take rapamycin, but not for osteoporsis. Is there any evidence that rapamycin affects bone loss in any way, positively or negatively. Thanks very much.

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#35

I’d like to better understand what rapamycin is doing to the immune system to increase Tregs and improve people’s responses to vaccines, as in the Joan Mannick study and this study on rheumatoid arthritis patients taking 1 mg QOD.

I’d also like to know more about how the innate and adaptive immune systems work, what’s typically happening when a person has an autoimmune or vaccine-triggered immune dysfunction, and whether rapamycin might improve those disorders.

Also would be interesting to know whether weekly, low-dose rapamycin can exacerbate an existing immune dysfunction and inflammation and, if so, why. (I think it did with me, but I plan to try again at a much lower dose while monitoring CRP closely.)

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#36

What do you mean by this?

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#37

My second Pfizer vaccine in 2021 triggered myocarditis requiring hospitalization. I recovered within a couple of months and had a good year or so, then it happened again about 2 weeks after recovering from a mild Covid infection (though my PCR test at the hospital showed I was still positive), that time with painful vasculitis-type symptoms that lasted over 6 months. I now have recurring episodes after any virus, with Covid-triggered ones being the worst, but they’ve been milder than the first two episodes.

This is the whole reason I’m taking rapamycin. I tried metformin first, and it helped tremendously with some of my chronic symptoms, but did not prevent future episodes.

I know of one other person on this forum who had a similar vaccine injury–recurrent myocarditis from the flu vaccine 20 years ago–who is taking rapamycin for the same reason.

#38

Interesting, what was the intended purpose of the Metformin?

Did you have Covid at all before the vaccine?

#39

@Krister_Kauppi i think you have enough ideas here to keep Matt busy for a long time.

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#40

How old is too old to start Rapamycin? Is 75 too old? What factors should be taken into consideration when evaluating whether the possible benefits would outweigh the possible risks in an older person? Knowing everything you know, would your yourself start taking it if you yourself were 75?

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