Cellular switches may control gene rejuvenation dosing

Transcript

Transcribed by machine (Whisper) from the episode’s audio, so a word may be off here and there.

1. 26:23

   is on the horizon so you've had this profound set of experiences with psychedelics you've documented in a very extraordinary and exquisite fashion all of the other things that you've been doing as interventions are there other things that are on the horizon yeah that you're either excited about or that you're considering yourself yeah i mean two of the ones that we've spoken about cell therapy and gene therapy yeah yeah they um they're all in the pipeline so they're not ready yet we've we've knocked out all the stuff you can do today like we've gone through it all done it all um the next gen therapies are just not there yet so we're looking at mitochondrial rejuvenation i think that's incredible i think mitochondrial augmentation therapy and there was a paper i saw where in order to get the mitochondria in the cell,

2. 27:05

   they coded the mitochondria in effectively a red blood cell envelope, which made it more transportable into cells and less attacked by the immune system. Yeah, exactly. Which is incredible. And I'm a big, big, big believer in this course of therapy. I mean, it's gonna be a whole therapeutic modality that no one has even recognized. I agree. We have our first mitochondrial therapy lined up. So how are you gonna do it?

3. 27:26

   You're like 99.9%. You need someone who's like 48.7% to try the mitochondrial, particularly like, you know, I think they tried it in Parkinson's patients, Alzheimer's patients. That's where you can really see profound shifts in, in certain metrics for you. It's like 99.9 to what? Like, yeah, yeah. I had the mitochondria, you know, of a 48 year old, right? So like, what, what if I, what if I connect? Yes. You could go to your sibling's child because the mitochondria is passed maternally because it's in the, it's in the egg cell yeah so it's the mother's mitochondria so if you go to In the mother's line maternally, if you have a sister who has a kid, they're going to have very young mitochondria.

4. 28:06

   You can take a little blood sample and then grow their mitochondria extensively and use that as a biological match to you. This is a perfect extension. I've had a blood boy as a son. Yeah. So now I'm just going to go to the extended family and be like, guys, it's a family project. Yeah, family project. Yeah, exactly. Yeah. Well, that one's super interesting. We also have one that we're doing. I'm now building.

5. 28:27

   sorry are you going to do your own mitochondrial transplantation you're going to build a bioreactor are you using working with one of the third parties yeah a third company yeah so i'll get i'll do a blood draw in the next week or two they'll spin up and they'll do it yeah okay yep so you're going to get your mitochondria which have some you know the problem with mitochondria as you know is mitochondrial dna degradation over time right it accelerates for certain people but that way if you go back to a young person you have young mitochondria exactly then you're going to multiply yours out yes and probably select a little bit or exactly healthier ones yeah right okay and then so it's very i mean exploratively like we don't know uh we're one of the first they're they're in phase two now do you sprint yeah i do so you could probably score if you did

6. 29:08

   it intramuscular like mitochondrial therapy you could sprint your score that's a great idea yeah thank you yeah yeah that would be a great way to measure it from a rather than just a basic biomarker perspective be really interesting to see yeah sprinting is one of the most underappreciated longevity therapies yeah i i don't do it oh i've got the um the age of a 74 year old uh roughly i am uh i'm definitely not keeping track with you would you consider or have you looked at any plasmids where you take a gene as dna put in your body and then that gene makes a protein in your body that that does something like the one we were looking at in the foxhole 3 expression yeah exactly so the mesenchymal stem cells it packaged up with the foxhole 3 delivery um you know that showed that over 50 percent of tissues getting that rejuvenation it's

7. 29:54

   unbelievable unbelievable it's like the unbelievable it's the best demonstration in the entire world that's perfect for tissue regeneration like as a particular application set tissue regeneration using that sort of system seems like a no-brainer it's like yeah it's safe right it's like yeah yes i uh reached out to that chinese professor i'm really interested in seeing it replicating i would love you reached out to the chinese professor yeah it's awesome yeah we sent that paper yeah yeah yeah that's awesome so did he respond uh yeah awesome yeah good uh so we i'd love to do that um i'd love to actually build it ourselves yeah but that's like a two-year project so um ai can help make it fast that's true yeah actually that's true ai as a project manager for these sorts of programs is you know that's true we spoke about this six months ago

8. 30:37

   yeah and things are so different so different now six months later and in terms of stand that up um so that was cool so i think that's a good good option but also i'm doing uh brian johnson organoids so uh we took my ipsb ipscs we now have induced pluripotent stem cells exactly so you took your cells turn them into stem cells yep yeah so now we're doing in dish so now we have like a brian johnson heart liver lungs and now we're going to try molecules on me and in so you have a plot so let me just walk the audience through this so you take cells off of your skin or something blood and then you put these yamanaka factor proteins on those cells causes those cells to become stem cells which means they can then turn into any other cell yeah and then you put other proteins on them to turn them into a heart cell or a eye cell or what have you and now you've got

9. 31:18

   a store of these tissue specific brian johnson cells yes that you then use for like you can say okay uh what if you get brian johnson blank you know drug what is what happens is it good is it bad what are the side effects in the petri dish you put the drug in there exactly see what happens yeah okay like you can simulate all these experiments so now you you get the advantage of time of acceleration of like what to take why what dose that's awesome what combinatorial things to consider yeah and so we we have the organoids stood up we haven't done our first takes yet yeah so that's interesting because now i have to do this old school methodology like put it in my body wait to see what happens is it good is it bad what you know how does it affect everything Yeah, totally.

10. 31:59

    Totally. But I mean, I don't know. We'll see. It's cool in concept. I mean, TBD, if it actually works. So we'll see. Have you tracked any of the alternatives to Yamanaka factors, the factor discovery work that's going on? And do you think there's anything worth testing at this stage? Yeah. I'm an investor in New Limit. So I've talked to them about where they're at. Blake and Brian's company. They've done, I mean, they've made remarkable progress.

11. 32:22

    They figured out how to computationally solve the discovery process. yeah and so they um they're much faster than they initially thought and so that's very encouraging you know the big challenge with young monaca factors is always dosing if you overdose a cell a one cell that cell can become a cancer cell and take off as a tumor yeah so the sensitivity that you need to have to get the right number of the factors which is a protein into the cell needs to be perfectly tuned yeah so i have a theory that this will end up being solved by cellular switches that will end up putting machinery into the cells that can turn on or off the protein synthesis at the right dosing based on the measurement of gene expression in the cell.

12. 33:04

    That's my theory on where this will end up. That makes a lot of sense. Any other control mechanism will be inadequate. That's right. All you need is one error and you're in trouble. But it is the most profound, I think, technology that humanity is dealing with today besides AI. We're not quite there with fusion, which I would argue is probably a distant third, but it is very powerful in what's possible.