#41

there is evidence to suggest that mTOR inhibitors might be cardioprotective.

In heart transplant recipients, mTOR inhibitors have consistently demonstrated beneficial effects on cardiac allograft vasculopathy (CAV).

…investigated cardiovascular outcomes in sirolimus versus control. There were no differences in myocardial infarction, abdominal aortic aneurysm, cerebrovascular accident, and congestive heart failure incidences between the two groups. However, the sirolimus cohort was older, with higher proportions of pre-transplantation hypertension and diabetes and post-transplantation hypertension compared to non-sirolimus controls, which might suggest that sirolimus was cardioprotective despite the higher incidence of hypercholesterolemia.

Nevertheless, we cannot establish a causal relationship between mTOR inhibitors and worse cardiovascular outcomes compared to CNIs with our large database analysis.

#42

I also found the interview interesting. But the point regarding CR is a misunderstanding many prominent people repeat.
The reason its sometimes negative is simply because for those animals the 30-50% was too much for them to handle. If you took those animals down to 15-20% their lifespan would likely increase just the same. CR is not some unstable boomstick.

Not to mention theres many studies where the lifespan is pretty much extended across the board.

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#43

“Optimal” could be for different conditions or situations. Going back to your Pankaj interview, his 14 day 1mg rapmycin / 14 days off seems primarily to be preventive. A long term lifestyle solution. And he is directly confronting his tendency to over eat with fasting and high blood sugar with his supplement. He also stated that someone with different medical condition might need another strategy than his. So parsing out from your interview, he seems to have a well thought out strategy (optimal) for a healthy 50ish male who likes to eat. I also think he is not entirely forthcoming on his strategy. He has access to scientists in his field who can directly guide his thinking. That is not a criticism about not being forthright. I think he has avenues of thinking that are too early and iterative to state in an interview.

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#44

It would be a failure to grasp the hierarchy of evidence to use a study of atherosclerosis in mice (which don’t even naturally get atherosclerosis) to draw a conclusion directly opposite to known facts about atherosclerosis in humans. But the point is moot, because rapa doesn’t raise LDL in these mice, contrary to what Blag is here saying:

Importantly, total serum cholesterol level in fat-fed mice was not affected by systemic treatment with rapamycin at 1 and 4 mg/kg (RAPA1 and RAPA4, respectively, p>0.05 vs. control fat-fed mice) (Fig. 1A). Likewise, the amount of cholesterol associated with discrete lipoprotein fractions of fat-fed mice was unchanged in rapamycin-treated versus untreated mice (Fig. 1B). Thus, rapamycin does not affect lipid profile in fat-fed apoE-null mice.

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#45

And just for reference if anyone wants to see what a young Dr. Kaeberlein looked like:

image

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#46

That pic makes Matt’s personal testimony (from one of his podcasts) of being a bit , wild, rogue, and unfocused as a youth… much more believable. Hahaha.

I think he needs to go back to a scruffy beard look.

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