Calorie restriction, fasting, rapamycin with Matt Kaeberlin

[Mike41]

 

[mccoy]

I've listened to Peter Attia's podcast with Kaeberlin. I'll have to listen to this one as well. According to Kaeberlin Rapamycin is not so potentially dangerous as believed, in the right intermittent doses. The study on immune response after flu vaccination of rats would support this idea. Of course, most researchers believe that what they are studying is the best substance or intervention...

 

https://peterattiamd.com/mattkaeberlein2/

Edited October 26, 2021 by mccoy

[Saul]

Matt Kaeberlein lectured at one of the earlier CR Society meetings.  More recently, he was invited to present the principle lecture at the annual anti-aging conference, that we have every year, in the biology department at the very end of the Spring term.

As usual, I attended this annual conference -- just pre-pandemic.  Matt gave the same talk here in Rochester.  He is currently testing the use of rapamycin on large pet dogs (the only way he was legally able to do this without extensive approval hearings was, that he made it volunatery for people who wanted to try something to attempt to extend the lives of their pet dogs.  The dogs live at home, and come in for their dose; some of the dogs are given placebo.  the trial is double blind).  (Large dogs are a very intelligent choice:  They are large mammals, so closer to us than mice; and (unlike small dogs), large dogs normally have a brief lifespan.)

I asked Matt after his talk how he thought rapamycin would work together with Calorie Restriction -- he answered that he could never get money or permission to do such a study (he is not on CR himself).

I should point out that rapamycin came up during the question period of one of the CR Society meetings:  It was noted that, of all the various drugs that supposedly might lead to life extension, it was the only one that really did seem to have that effect in mice.  I remember expressing skepticism at that meeting.  Luigi Fontana and others disagreed with me -- they pointed out that the data so far is positive.

I would take Prof. Kaberlein's studies seriously.

  --  Saul

[Guest]

The question is: does Rapamycin work in humans for life-extension or disease-mortality similar to what studies in mice suggest.

 

Sure: if Peter Attia takes 6 mg of Rapamycin once a week it does not have much side effects. But does it have any intend effect at that dose either? I did some rough calculations based on a paper of Kaeberlein some time ago - as it turns out the mice are getting an enormous dose of Rapamycin by 3 different metric. Far more than Peter Attia is reportedly taking:

https://www.longecity.org/forum/topic/89073-new-rapamycin-study-up-to-60-increase-in-mouse-lifespan-anyone-experimenting-with-this/page-25#entry876052

 

So given the lack of evidence in humans or other long-lived animals, there seems to be little basis on taking something like 5 mg to 10 mg of Rapamycin once every 7  days. Little side-effects. But probably also little effects.

[Todd Allen]

On 10/26/2021 at 4:17 PM, Saul said:

As usual, I attended this annual conference -- just pre-pandemic.  Matt gave the same talk here in Rochester.  He is currently testing the use of rapamycin on large pet dogs (the only way he was legally able to do this without extensive approval hearings was, that he made it volunatery for people who wanted to try something to attempt to extend the lives of their pet dogs.  The dogs live at home, and come in for their dose; some of the dogs are given placebo.  the trial is double blind).  (Large dogs are a very intelligent choice:  They are large mammals, so closer to us than mice; and (unlike small dogs), large dogs normally have a brief lifespan.)

Do you know if diet is factored into the Rapa study?  It wouldn't surprise me if Rapa's effects were different in dogs eating highly processed high carb commercial pet foods versus dogs eating low carb commercial pet foods and those eating non-commercial natural whole foods.  Even if it was only observational diet data I'd expect there would be value in knowing what the dogs were eating.

(EDIT)

I broke my YouTube boycott and watched the video Mike posted.  Thanks Mike, worth the time.  And it sounds like the answer is yes, Matt's dog aging project is collecting extensive data including diet and feeding patterns.   Rapa is only in a fraction of a larger cohort of a project with both observational and intervention components.

Edited October 29, 2021 by Todd Allen

[Guest]

I know that people are in love with their dogs and Kaeberlein is a well known guy.

 

But please do not forget the ongoing rapamycin-longevity study in marmoset monkeys, which aims to determine life-extension and health outcomes of rapamycin in short lived primates:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415526/

 

They started the primates at 8 years of age and are already running the intervention for 2,5 years. Marmosets have a typical life expectation of 12 years - so the results in primates will be available before the dog-project is over. The team at the Institute for Longevity and Aging Studies at UT San Antonio is also invovled in running experiments for the Interventions Testing Program of NIA; so they have some experience.

 

So please - yes, dogs are interesting. But the rapamycin lifespan-study in primates (finishing soon) are more relevant for humans - don't you agree?

 

[Saul]

Yes.  Fascinating stuff -- even Luigi believed that rapamycin might really work in slowing aging.  (I'm an agnostic.)

  --  Saul

[BrianC]

Is anyone here practicing CR and taking rapamycin?

[Saintor]

Interesting read.

https://financialpost.com/news/did-a-canadian-medical-expedition-lead-to-the-discovery-of-an-anti-aging-pill

However, according to it;

There’s one catch: Rapamycin suppresses the immune system

[Saul]

17 minutes ago, Saintor said:

There’s one catch: Rapamycin suppresses the immune system

Yes; but, as noted by Kaeberlein, this effect is vanishingly small for healthy people.  So, for most of us, this is not a "catch".

The question is, does rapomycin really extend healthspan and lifespan?  There isn't enough evidence in humans.  Kaeberlein figured out a legal way to test the effects on large dogs.  In a couple of years, we'll have that data.

What is clear, calorie restriction is the gold standard of health, and possibly, life extension.  Luigi's testing of CR subjects gives strong evidence for this in humans.  (But, possibly, rapomycin -- or some artificially modified version af rapa, might be useful for life extension.  No question though, for those who can control their intake of food, CRON is best.

  --  Saul

[Guest]

I just want to reiterate, that there is another "legal way" of testing rapamycin - primates.

 

While the dog-trial did not yet start, there is an ongoing lifespan trial in a species of short-lived primates, done by an established aging-research team:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415526/

 

Their results will be available before the dog-trial is going to be finished. I'm not an expert, but I think that their data from primates might be almost as relevant for humans as data from dogs - though maybe somewhat less, because they don't have a brand-name research star on their team and don't constantly talk about it on podcasts.

 

Also if I recall correctly, CRON introduced in aged mice does not extend lifespan. On the other hand rapamycin administered starting at old age (in mice) did.