Drop some burning questions for Richard Miller below!

I am speaking to Dr. Miller soon about the ITP. Let me know if you have any questions so I could forward them his way!

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Does acarbose work on fruit sugars or on fats? Does its effects on cap independent translation apply if you don’t eat complex carbs?

What amount of canagliflozin effects come from SGLT1?

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What are the compounds they will test in the near future?

Since they have shown Glycine increases life expectancy, will they test Glycine + NAC as this is supposedly a more powerful combination? (Glutathione replenishment)

Are they going to trial other combinations of effective therapies? Like Rapamycin+Astaxanthin?

Would access to large data-mining and machine learning AIs help the ITP research? If so, I may be able to help arrange something through my connections (not guaranteed though)

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Don’t know if I will be able to ask about that or share that here because it lingers into the realm of unpublished data. Sorry.

Here is the answer to that last question: Anti-aging conversation with Dr. Richard Miller - YouTube

Seems like ML people don’t really know what Dr. Miller needs and Dr. Miller doesn’t really know what ML could offer. So for now it doesn’t seem all too critical for the ITP.

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That is the rub. Machine learning is best for doing repetitive boring tasks such as spotting cancer tumors on X-rays. So, if there was a way to do a full CT scan of the rats (alive or dead), those scans could be examined by ML AI to determine the cause of death. This information may or may not be useful. (I.E. If the rats died of a certain type of cancer or another disease with Rapamycin, then a compound that addresses that cancer in conjunction with Rapamycin could be used to extend life further.)

In addition, if there were other factors that could be measured by optical or medical scans, AI would be great at parsing the data. This could be things like bone density, hair pigmentation, etc… I’m not a doctor, so I don’t know what other factors could be measured and examined by scanners to determine the overall health of a rat. Right now, lifespan is the only thing being measured, but maybe some other factors could be useful? I’ll leave that to the docs…

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That being said, would you like me to ask automated collection/analysis of what biomarkers / phenotypes would help the ITP interperet their drugs better? Is there a better way of phrasing this?

Yes. But I think someone with more medical knowledge needs to suggest it. :slight_smile:

One question is will they ever look at things other than oral delivery? How about injection or other delivery methods?

Also, combinations of more than two drugs at once?

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I don’t think they’ll be catching rats and injecting them daily. What a job!

Acarbose is not a fructokinase inhibitor. It’s an alpha-glucosidase inhibitor.

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Let’s say someone had a dear pet mouse and wanted to apply the ITP learnings as best they could in 2022, what combination would he recommend as an ultimate (mouse) longevity stack?

the ones we all want to know are rapamycin + 17-alpha-estradiol and rapamycin + very low carb diet (with the fats not being seed oils of course in both the intervention and control arm)

edit: and please add an overview of all the substances tested and the results on the NIH ITP website (with link to relevant publications)

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I’d like to see:
rapamycin + 17-alpha-estradiol + canagliflozin
rapamycin + 17-alpha-estradiol + acarbose
rapamycin + 17-alpha-estradiol + acarbose + astaxanthin
etc…

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How about just video-record everything the mice do (motion capture). That’s what Ora Biomedical is doing and allows for more detailed and immediate analysis beyond just lifespan

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yeah but that’s going to take a lot of mice (lab space/work/budget)

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In the Metformin trial two of the labs showed a positive increase to lifespan. The third showed zero effect and so the conclusion was no effect. In the rapamycin/acarbose study, one lab also produced anomalous results, but here the effect was overly positive to the tested drugs. The paper was produced showing the results of only two labs.

Do you only disregard potential issues in the testing procedures of a single lab when the mistake renders the results overly positive? How do you explain your decision to publish a report relying on the results of only two labs in the latter case and not in the former?

And to add to RapAdmin’s post:

Rapamycin + metformin + Acarbose

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Do you freeze the tissue so it can undergo further “omics” analysis (eg metabolomics, transcriptomics, proteomics, epigenomics + spatial transcriptomics + everything in Wyss-Corey papers) and also get body composition of them measured?

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Just to follow on this excellent question - When are they going to start doing this type of “multi-omics” analysis on the mice tissues to help refine and perfect and test biological clocks. These ITP studies are perfect for this type of effort!

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