Ora Biomedical launches crowdfunding of Million Molecule Challenge

I buy citrate in bulk (25kg) (some hydrous some anhydrous) and it costs about GBP 15 per kilo. Obviously smaller quantities would be more expensive per kilo.

In the end, however, I have my own small biohacking trial that is gradually increasing in size so I am not particularly bothered what effect it has on worms. I would pay them a reasonable amount for a test, however.

Citrate is solidly GRAS. When people have a blood transfusion for example, it tends to be infused with sodium citrate which is also used to make Nachos. (the formula is Na₃C₆H₅O₇) Given my experience with eating insane quantities of citrate I wonder sometimes if one of the benefits people get from a blood transfusion arises from the additional gene expression from the citrate.

I see no merit, however, in me giving them funds to test anything else just because the test is cheaper.

They do have C₆H₈O₇ on their list (Citric acid, Citrate plus three separate protons) the main acid in Lemon Juice (and Lime Juice/Grapefruit Juice).

However, I think eating a lot of acid would be something I would not wish to try. Cells deacetylate the histone to increase the pH which would be a really bad thing.

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What biohacking trial is it that you refer to? Is it the MN=1 that we talked about?

I don’t see any conflicts with that human trial and large screening in worms. As I see it the screening will open up totally new territories in the longevity field that we have not looked at yet. If we would for example get a really large combination effect of one FDA approved drug and Rapamycin then that combination would be very interesting to do a ITP on and see if the effects also exist there. This way we come step by step closer to human trials and move the field forward.

Curious question, do you see very little value in doing large scale experiments in a cost-effective way where Rapamycin is combined with FDA approved drugs and natural compounds? What would be needed to increase the perceived value for you?

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No its not the MN=1 trials that we will be doing via rapamycin news. It could be one of those trials, but as it is my own personal hypothesis I think it best that we start with something else.

I have a small group of people - mainly friends and family - that are following the protocol to improve gene transcription (and translation). I don’t mind if more people join that, but what I have suggested as the first MN=1 trial relates to Rapamycin.

The reason why I personally am not particularly interested in testing lots and lots of molecules is I have a clear mechanistic hypothesis (transcription/translation) where it is clear what you can do that is synergistic and it produces good results. Hence I personally want to focus on this. Rapamycin is part of this because of its effects in mitochondria.

Because we are doing that testing in human beings, therefore, there is a lesser, but non zero merit in having some worm testing.

In the absence of a realistic practical hypothesis the approach of testing very large numbers of molecules has merit and I am not saying to anyone they should not do that. However, my situation is different.

Because I don’t need any funding (I am self funded) and I already have people in my biohacking trial I am not really beating the drum for my protocol. What I need to do is to get on with the testing. It is quite complicated because it is multidimensional and has two main pathways. Hence in transcription there are issues about levels of acetyl-CoA, RNA, HDAC inhibitors and also I think serum Lithium. In translation it is all about mitochondrial efficiency, but a lot affects that. Hence I am testing out lots of different approaches in terms of dosing, timing and combinations.

In the mean time I have to get on with life as well. I am a tech entrpreneur and investor as well as a musician and I have five children - only one now under the age of 18. Hence I am quite busy.

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From their materials:

And by “better” we mean larger effects on lifespan and healthspan – because that’s what we care about. How can we be so certain? Because just from a small pilot screen of a few mTOR inhibitors, Ora has already identified one that works better than rapamycin.

What would that be?

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Just sponsored one. Hope they get tons of people funding this!

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I find it rather amusing that this week Matt and Brad Stanfield chose colchicine as the medicine to test in the wormbot.

Given our recent conversation about this drug:

Of course, more broadly it looks like an interesting drug: Gout Medication Colchicine Reduce Myocardial Infarction? 2019 N Engl Journal

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I think Rapamycin + Taurine is going to be a winning combination. Let’s see if I’m right.

Seems they’ve raised about $860,000 through this challenge in 2 weeks. Honestly, this is the way to raise money for longevity research.

I’ve supported the Million Molecule Challenge! https://orabiomedical.com/product/double-compound-intervention/… #millionmoleculechallenge via

@OraBiomedical

How do we find the leader board?

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Based on how toxic colchicine can be, I think that wasn’t the best choice by Dr. Brad. But, why not give it a go anyways…

I supported them too. Not a biologist so I let them choose; would be interested in seeing what I (and others) have ended up selecting.

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Longevity is a perfect match for this strategy. We know that the basic pathways are conserved across evolution all the way back to really simple organisms. And it’s pretty easy to tell whether a worm is living or dead. So you have an automate-able endpoint and a simple model organism with a short natural lifespan and you can just go to town. Really genius stuff.

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Did you bet on Rapamycin + Taurine? just to make sure I understand the competition :slight_smile:

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I did. I paid $200 to do the combination of the two chemicals.

Frankly, I also want to know the answer personally as I am taking both compounds daily. It’s about as expensive as a blood test, and in some ways more informative. Rapamycin and Taurine are the two supplements I take the most of. I want to know if they work well together.

I recommend others do the same if you are taking a few supplements together.

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One question I had: what happens when multiple people choose the same protocol? For instance, I can’t believe that the rapa/taurine combo hasn’t been submitted multiple times already??? What then? How/where can one find out what protocols have been selected to be tested?

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The single drugs have ‘sponsored’ in the title when choosing them, at least.

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I think once it is sponsored it’s been claimed. Only one sponsor per protocol.

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Not sure if they do the same with multiple drug combinations though…

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I am talking them about doing a mixed citrate test. It seems to have gone a bit quiet though.

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I sponsored Circumin. I’m about to publish a podcast with Ora Biomedical’s CEO, Mitch Lee (PhD) about the worm bots and this new program. We also get into how to think about using and combining chemical interventions (if you dare).
Hint: avoid targeting the same aging hallmark or mechanism too much (e.g., Rapamycin plus several other hits to mTOR = red zone).

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Curcumin is a good thing to sponsor. It is a Histone Deacetylase Inhibitor (HDACi). It does other things as well. I am currently testing about 15 HDACi s. My theory is that they have a synergistic effect whilst each one has minimal side effects because the quantity of any one HDACi is relatively low.

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@John_Hemming Thats great to hear. What are your thoughts about spreading our small molecule interventions around multiple “hallmarks”? …to get a larger overall benefit without getting excessive (maybe harmful) effects on any one mechanism?