#21

Ask Matt what his activities are in his new job at OptiSpan, and what the company’s focus is on the next year…

Ask him about progress at the Wormbot company he’s co-founder in, Ora Biomedical, and when some results might be announced…

Matt is an advisor for Loyal for Dogs which has announced that they are doing an FDA-approved clinical trial for an IGF-1 inhibiting drug to slow aging in larger drugs. Can Matt share the name of this drug / compound that Loyal is trialing? Is this a repurposing of an existing drug that has been used in humans for another purpose, or an entirely new compound that hasn’t been marketed at all before? Can you share any details on the compound or the Loyal clinical trial?

Oh - more generally, you might ask about what are all the companies he’s an advisor to or co-founder in. I know about Ora Biomedical and Loyal for Dogs, but perhaps there are others that are interesting.

Also - besides the already identified pro-longevity compounds alread identified by the NIA ITP, what compounds or drugs does he find most interesting as potential new longevity compounds?

What newer longevity-focused companies does he find most interesting?

Oh - and I recommend you email Matt a list of your interview questions a week prior to your discussions with him so that he has time to think about them, prior to answering.

and another: The biggest risk with rapamycin seems to be potential immune supression at higher daily or regular dosing. Rapamycin News spoke with Adam Salmon the other week and even at the high dose of 1mg/kg daily dosing in the monkeys, Adam suggested that they are definitley inhibiting mTORC2 substantially at this level, and they see some signs of immune supression, they don’t see much suppression from what they can tell. How much do you think rapamycin actually decreases the immune system at higher, regular dosing and what does he think the real risks are in this area? Can he recall the best studies of rapamycin being used as an immune system suppressant by itself?

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#22

Yes, I’d really like an update on the wormbot project as well!

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#23

I think there are some people who are wondering if the high dose would be able to accomplish more than multiple low doses. However there could be good and bad effects associated with the higher dose.

I would also mail all the questions to Matt early so that he can contemplate them. Thanks Krister for all your efforts!

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#24

As a researcher studying Rapamycin for longevity, based on your knowledge of biology, what are the main biological limitations or potential barriers that may prevent Rapamycin from being an effective means to extend human life and healthspan?

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#25

What are the current limitations in our understanding of how Rapamycin works to extend lifespan, and what additional research (apart from the dog aging project) needs to be done to address these limitations?

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#26

  • How fasting (both 1-3 days and 4-5 days, water only) may optimally be combined with weekly or no-weekly rapa? Eg thoughts on potential sequencing/timing of each that might be most synergistic?

  • Thoughts on how synergistic, additive or just overlapping (mild) CR and rapa is in healthy humans?

  • Thoughts on cycling not just weight lifting to be most intense days away from taking rapa, but also cycling protein (and especially BCAAs) to be highest the days that are away from taking rapa.
    — In order to align when the body is in (i) build/grow/mTOR high mode vs (ii) repair/recycle/rejuvenate/autophagy/mTOR(C1) low mode

  • What ITP molecules is he most excited about if one takes rapa out of the picture? What one(s) might have the most synergistic effect with rapa in healthy humans? Does he think acarbose and Cana have longevity effects beyond the ability to decrease glucose spikes (and perhaps average glucose)?

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#27

Question:

Since older mammals have more mTOR activation, would it make sense to have a mice longevity study where the dose increases/doubles every 90 days? (10 mouse years)

So start on low dose at 9 months of age and increase/double every 1.5 month.

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#28

Really interesting dose regime!

By the way, do we know that mTOR activation increase the older we get? Is there any studies on that?

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#29

These three please. Also I’ll take the second question further: granted that he’s more excited by rapa, which of the compounds that have already been well-validated in animals does he think are most exciting for potential human translation?

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#30

Ask him why does metformin + rapamycin produce life extension beyond just rapamycin alone.

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#31

Or acarbose + rapamycin. I assume it will be similar.

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#32

Yes: lots of studies on this, in both mice and humans — liver and muscle:

mTORC1 controls fasting-induced ketogenesis and its modulation by ageing

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#33

I had some questions on a similar thread eariler. And they still remain unresolved for me personally. So I’d love if you could bring this up with Matt Kaeberlein

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#34

The enigmatic Rapamycin may be the key to unlocking the secrets of Easter Island, and the mysterious longevity cult said to have resided there, before ultimately succumbing to its mysterious fate.

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#35

Where do we find the podcast?

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#36

He hasn’t interviewed Matt yet…

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#37

You can subscribe to his youtube channel : KristerKauppi

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#38

Here is the link to the youtube channel

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#39

His opinion of this:

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#40

Matt has already posted commentary on that study, see here: Rapamycin increases Alzheimer's-associated plaques in mice, study finds - #25 by RapAdmin

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