Rapamycin Webinar and Dr. Green

I wonder, with all the Rapamycin human studies out there…if we looked at actual cause of death, is immunosuppression causative? Can one definitely assign death to an aspect of the immune system?

Appears you can.

Long-term Follow-up of a Randomized Trial of Tacrolimus or Cyclosporine A Microemulsion in Children Post Liver Transplantation

“There were 11 deaths in the cohort, which were from infectious complications/malignancy in the Tacrolimus group”

Another large observational study:

“We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401 infections and experienced 1,045 infection-related deaths. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and
reverse causation”

Looks like 1.1 lymphocyte count is a significant HR association cutoff.

Lymphopenia was, after weight loss, the biggest Grade 3/4 side effect (n) in the cancer/Sirolimus/GFJ study.

From a Lamming paper on Rapamycin/mice/longevity and TOR2:

Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity

“Our results suggest that rapamycin extends lifespan at least in part via inhibition of mTORC1, and despite impairing glucose homeostasis via disruption of mTORC2 signaling. Chronic rapamycin treatment disrupted the association of mTOR with both Raptor (mTORC1) and Rictor (mTORC2) in all three tissues. Therefore, direct disruption of mTORC2 is a second molecular mechanism that may contribute to the effects of rapamycin in vivo. Our findings emphasize that mTORC2 disruption profoundly affects metabolism, and may be relevant to the pathogenesis of type 2 diabetes and the metabolic syndrome. Rapamycin disrupts mTORC2 in multiple tissues. Disruption of mTORC2 may contribute to the pro-longevity effect of rapamycin. mTORC2 disruption is an important mediator of the effects of rapamycin in vivo

The “practical” issue is all we have readily available is Rapamycin (and Everolimus), both of which impact TOR1/TOR2 in cancer curative studies.

What about prevention?

Are we truly harnessing Rapamycin without teasing mTOR2, or just fooling ourselves at low intermittent doses?


Some good observations, studies, and thoughts. Thanks.
It’s seems reasonably clear that chronic inhibition of TOR leads to disruption of Rictor and secondary inhibition of TOR 2.
It’s certainly conceivable that weekly dosing will inhibit both TOR complexes to variable degrees.
It’s hard to know what’s meant by chronic dosing. I’ve been on it weekly for 5 years. Is that chronic enough to affect TOR 2?
Also, if we’re totally inhibiting TOR 1 for several days of the week and then partly for a couple more days, is that chronic inhibition?
My glucose has gone up from 99 to 112 on rapamycin. And that’s with regular exercise, watching my diet, and weight loss. Metformin didn’t affect it. So is that a TOR 2 effect?
On the other hand, no infections.
My suspicion is that rapamycin is an anti- cancer agent at even low doses weekly. But is it a longevity drug at those doses? I don’t know.

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Back to throwing darts…we just don’t know.

If your glucose and lipids aren’t both dysregulated, then would not suggest much TOR2 impact.

I had an Apo B done about six months ago just to see and it was 113. I don’t have a prior level but I suspect that that’s high for me since my lipids prior to rapamycin were always pretty good. I bet it’s up about 15% similar to my glucose.

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We need more people posting, collating data, and doing mTOR1/2 assays!

How about your trigs?

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I haven’t checked my lipids for about 15 years. I’ll check it soon.

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Rapamycin for longevity: opinion article Mikhail V. Blagosklonny1

The rationale is to get a big spike of Rapa past the blood/brain barrier in the brain to get maximum MTor inhibition. There have been some rat studies that did this to reset the “weight point” lower to live healther. It worked. Also, some believe ageing is controlled in the medulla oblongata. Green tried 20 mg + every 2 weeks, but got some side effects, so he went back to 12 mg. weekly. He is treating ageing, but a heart condition also, and he is almost 80 yo. I am going to have to watch that last AMA. I did not hear that Dr. Green is taking 12 mg two days in a row. Remember: He is treating a heart condition also.

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Exactly “opinion”. He’s an n=1 just like Dr Green.

We still have not seen the definitive Rapamycin matrix that results in full on escaping all the hallmarks of HUMAN aging.

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I’ve been considering extending the dosing to 3 weeks. Currently I’m at 10mg + GFG, which is an effective dose of 35mg (probably, hopefully), once every 2 weeks. But I want to make sure I get to a trough. So yeah, it feels like B moving on to daily dosing cuts backwards against that trend.

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Given the lack of clinical study data we have in this area, I think we are all doing our own personal SWAG (scientific, wild ass guess). I think the key is to do our regular blood work to track results and adjust as necessary. The open issue, I think, is exactly what blood tests beyond CBC, CRP, perhaps trough levels of blood sirolimus, etc. that we need to do.

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It’s the “adjust if necessary” is a quandary?

Adjust to what and to achieve what longevity target?

Is dose limiting toxicity a meaningful target for prevention?

TOR1/TOR2 assays would be nice.

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Here’s the list Dr. Green gave me to test: Insulin, CMP, Hemoglobin A1C, Lipid Panel, CBC, and Ferritin.
Does anyone think it important that I also do C-reactive Protein, which I guess is what you mean by “CRP”?

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Kerry, do you have any concern that you might be getting close to the dose originally used for organ transplant patients to suppress the immune system? Especially in light of Covid still hanging around?

Yes hsCRP, would definitely add, and would add liver and kidney markers. Do a full iron panel, ferritin isn’t too meaningful. ApoB additional lipid marker.

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CMP (complete metabolic panel) includes liver and kidney markers

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Not really. Side effects(mouth sores, etc) give us a clear warning when we are intruding into Tor 2 territory. I increased my dose from 20 mg to 22 and could not sleep well for 3 days. Went back to 20. Transplant patients take “daily doses” to keep blood level high to prevent immune system rejection of organ. They are less concerned about side effects

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Curious as to whether you take the 20mg with grapefruit juice or any other bioavailability enhancer, or not.

I have taken both ways. Most people use GFJ for 2 reasons. If the cost of the Rapa is an issue or availability where you live. If you buy powder for appx. $70 gram which is equal to a 2 year supply then cost is not an issue. 1 gram rapa + 250 grams lactose powder = .25 grams mixture per 1 mg. rapa. = 40 mg. rapa per month(20 mg. twice a month) x 24 months = .960 grams of Rapa. Using GFJ would make 1 gram Rapa appx 6 year supply assuming 300% increase.


I didn’t hear about this webinar. Is it Available?