#7

Hi, long-time lurker, registered for an account to reply to this thread. A couple questions come to mind:

How does Matt think about the definitive human Rapamycin trial? If he were to design a study (with sufficient but realistic funding) how would he design it? What endpoints, aside from mortality, would he be interested in? What would the inclusion criteria be, specifically with regard to age?

A large portion of popular longevity content focuses on the anabolism / catabolism vector (I am not sure if ‘pathway’ is the right technical term here). Are there other key ‘vectors’ that Matt could talk about here that might be less discussed in popular media? I know this is a complex topic and many mechanisms interact; I’m mostly looking for additional lenses that can be used to assess potential interventions.

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#8

I may be mistaken, but I’m pretty sure Matt has commented on that trial before - short-lived controls meant he was skeptical it’d be repeated…?

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#9

Oh yeah, I’m an evil anarcho capitalist, I’m definitely gonna ask these ones!

#10

I think I need to tread carefully with this one? For some reason he walked away from the Dog Aging study, right?

#11

No - I believe he’s still involved somewhat, though his relationship may be a little different because he left U. Washington.

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#12

Actually, He’s still the director of the Dog aging project - He talked a little about it at Vitalist bay when I saw him there a few months ago - see his presentation here: Vitalist Bay, a Pop-Up City in the SF Bay Area - #47 by RapAdmin

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#13

He mentioned that he is considering 2.5mg Tadalafil daily.
Ask him to outline the reasons and any associated risks.

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#14

Yeah I just watched that yesterday. I duked it out with ChatGPT and turns out it was hallucinating. Now I’m a fool.

#15

What available drug/supplements might be complementary to Rapamycin in terms of mechanism of effect on health span?. What combinations might he think could be most effective. What should we avoid taking with Rapamycin? (I am particularly interested in drugs/supplements that could have side benefits for individuals with Long Covid, atherosclerosis and/or poor glucose metabolism.)

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#16

I’ll second these two questions on what which supplements would compliment, vs be redundant, vs what we should avoid, even if it’s only on rapa days.

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#17

You wrote: He mentioned that he is considering 2.5mg Tadalafil daily.

Ask him to outline the reasons and any associated risks.

Maybe this is a question for Tammy Kaeberlein… :laughing:

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#18

FWIW, I believe he mentioned tadalafil when discussing the study that looked at the association of medications people took and lifespan - drugs that showed life prolonging association in the UK Biobank study. There were a handful of such drugs, including atorvastatin, a couple of vaccines, and viagra. Tadalafil is a sister drug to viagra, but longer lasting in the body. So MK thought that interesting enough of a longevity signal to consider taking… so not so much for the sake of his wife as much as his life🤪.

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#19

Ask him to discuss mitochondrial transplantation and the energy theory of aging.

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#20

  1. What would be rapamycin schedule with iron-deficient low hemoglobin? Can rapamycin have a hormetic effect?

  2. What does he think about 3mg per week dosage of rapamycin?

  3. For starters, is it necessary to start with lower dosage and increase gradually (e.g. 3 to 5 mg)?

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#21

What data is there about Rapamycin blood levels. Is 24 hours post-pill a good sampling time. Does he have targets? If so, what are they?

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#22

Two questions: (1) Why does he personally cycle off rapa for 12 weeks (on 12 wks and off 12wks)? and (2) While he changed the dosing frequency for his canine study from the original 3x per week to now 1x per week (for participant feasibility reasons?), would he predict that the original 3x per week would be more effective in the real world for canine health and life span?

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#23

What’s his favorite colour.

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#25

Asking the real questions here. Anyway, wow guys that’s a lot of questions, we’ll see if I can keep him around for the full 8 hours hah.

FTR our conversation is on Wednesday, 16:00 UTC, so questions can come until then.

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#26

Ask him if he aspirates his TRT injections.

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#27

What’s your take on different ways of rapa administration, intra-muscular, intra-nasal…?