I get really frustrated that things go so slow forward in the rapamycin longevity field so it’s time to speed things up. This is why I now launch the Rapamycin Longevity Lab so that we together, people and organizations, can start moving things forward. (The real official launch of the lab is on Saturday)
The Rapamycin Longevity Lab has partnered up with Ora Biomedical and we will use their groundbreaking wormbot to do the following two revolutionary projects to start moving things forward.
Longevity Wormbot Program (LOOP)
This first revolutionary project is about setting up a yearly next level ITP but instead of doing it on mice we do it on roundworms. We can do around 4500 experiments for the same price as one experiment for the classic ITP. This opens up enormous opportunities to start screening in a way we never were able to do before in the longevity field. In the first LOOP we use Rapamycin and combine it with around 2350 FDA approved drugs to find what combinations have synergistic, additive, canceling or even detrimental longevity effects. When we have these results we can take steps to test promising combinations on higher species to see if we get similar effects.
Longevity screening of 200 mTOR inhibitors
In this next revolutionary project we will see what other promising mTOR inhibitors exist out there. Does there exist any mTOR inhibitor that outperforms Rapamycin? How good are rapalogs? We will get unique and important data that no one has seen before in the field. This is just a must do project. In a future LOOPs we can for example go through the top 10 mTOR inhibitors to see how well they also combine with FDA approved drugs.
These are the two first projects that the lab will focus on! But I need your help in this and the help will not need to be big because if we do it as a community we can start moving mountains with that power.
The first step is therefore to get people onboard the lab and become lab members for free. The goal is that we have at least 3000 lab members who are willing to fund 100 USD because if we are that many then we can together cover the cost for both of the revolutionary projects. So 100 USD is a very small price to fund for the results we will get. We just need to do this!
For joining the movement and making a difference visit the lab web page.
If you don’t have enough money to fund 100 USD in the future that is fine. There are many possible ways to help out in this movement. One simple way is to spread the word about this lab initiative. So if this is what you feel you can do then become a lab member too. Every small or big step is valuable when we do it as a community.
PS. I also want to point out that I or my company will not get any money from these two projects. The money will go directly to Ora Biomedical to conduct the experiments that we want them to do.
I think that the other thing that is missing in space of lifespan extension experiments would be validation of currently known interventions in other species (even across 3 different strains of worms would be a great move forward - now we have only drugs that work in C Elegans strain only)
For example, here there were tested 6 drugs by CITP that extended lifespan of C Elegans - but only 1 drug extended lifespan in all 3 strains of worms: https://www.nature.com/articles/ncomms14256
5 other drugs extended only lifespan for C Elegans - but not for C Briggsae and C Tropicalis
It would be good to replicate drugs like Rapamycin, Acarbose, 17 alfa estradiol and Canagliflozin across 3 different types of worms
I think it would be also great to start with compounds the most tested - because just testing drugs randomly has very low success rate (1 / 770 according to one test)
Testing Rapalogs, Acarbose, Canagliflozin, Rifampicin, lithium, Allantoin and combinations of these will be a great start and could lead to good synergies.
For example, there was a study that tested 88 000 compounds randomly, and it had 0.13% success rate - but when they tested only drugs when they knew their biological pathways, it increased to 4.7% success rate - it also shows these 60 drugs that worked in C Elegans
In these studies, 60/1280 screened compounds increased C. elegans lifespan, a hit rate of 4.7%. In contrast, when we previously screened 88 000 compounds of undefined function, only 0.13% (115/88 000) produced a statistically significant increase in C. elegans longevity. One possible explanation for this difference is that the 1280 compound LOPAC library comprises compounds with established biological activity whereas this is not the case for the 88 000 compound library
Very good that you lift that up! I talked to Matt Kaeberlein some days ago about what other possibilities there are when testing things in the wormbot. He mentioned that it would be possible for example to test different mutations and genetic strains. So that is a very interesting thing to look at in future potential projects because it’s very easy to get blind to just look at one thing. Great suggestion!
The really great thing with the wormbot is that we don’t need to wait until the full projects are funded before we start. We can start quite fast. My plan is to put in around 6000k this year just so that we can start getting some interesting results. So step by step we can move the projects forward. I really like your idea of prioritizing what should be tested and here we have a freedom of doing that also. So as a community we decide what to focus on first but also on an individual basis. Because let’s say you really want to see the combination effect of Rapamycin and Acarbose then you can just sponsor that experiment on Ora Biomedical for 100 USD.
Below is an interesting proof of concept that the wormbot team did in the beginning to test different combinations. To get this data on combinations with Rapamycin would be very valuable and give an indication on what to combine and what to avoid to combine.
I see such huge potential in what we can do together as a community when it comes to moving things forward. We just need to do this. My hope is that we get some really revolutionary data before the deadline for the ITP proposals in the end of February so that we can send in a proposal to them to test a promising combination
I see the biggest benefit of this sort of research is as a way to find the 100x better rapamycin. In my mind, so what if we find another similar mTOR inhibitor or a 10% better way to replenish NAD+. We already have 1000 ways to improve healthspan and lifespan 0.1% with diminishing rates of return for each (and probable negative interactions).
We need to find something surprising…shockingly good that doesn’t make any sense. Then the scientists can go figure out what is happening. It won’t help me, probably, but my children might live forever.
I am pleased that some people are looking at mTOR. I think inhibiting mTOR is part of what we are trying to do, but I don’t think it is even the majority. I think inhibiting mTOR is a useful part of improving mitochondrial efficiency (and the response to the ATP/ADP gradient and ATP/O efficiency). However, although mitochondrial efficiency is a key strand mTOR inhibition is only part of this. There is also the acetyl-CoA senescence strand.
@Joseph_Lavelle I really like your thoughts here! The next big thing I think will not be a single compound which will outperform Rapamycin. My feeling is that it will be a combination with Rapamycin or next generation mTOR inhibitors that may have a big effect. We have for example already indications on this from the ITP when Acarbose and Rapamycin are combined but I think we will do much bigger discoveries here. The really great thing with the initial projects in the lab is that we will get an indication around this. Nobody has done even anything close to the magnitude that we are going to do. We will get unique and revolutionary data in the field in a very cost-effective and quick way. The goal is that we get this data within 2-3 months and not have to wait for a frustrating year or years before we get this kind of data. With this lab initiative we will start moving things forward in a new way together as a powerful community and the ultimate goal is to solve the aging puzzle eventually once and for all. But to achieve that end goal we need to take things step by step.
@John_Hemming Do you think a combination of longevity intervention is a interesting aproach to handle this?
It would be interesting to test the best 3 drug combinations with even more candidates and validate this across as many strains of worms and flies as possible - because 1 test probably won’t convince NIA ITP
I think the more data, the higher chance of success:
Human data (if it works for any age related disease)
– Results from as many animals as possible:
Fruit flies (ideally multiple strains)
Different types of worms (C Elegans, C Briggsae, C Tropicalis)
If it would even with not perfect dose like Rapamycin or Acarbose - if something works only at specific dose, -/+ 20%, then it is unlikely to translate, Rapamycin in mice works both in 4.7 and 42 ppm - 9x difference, some studies used even 126 ppm dose and it still worked
Preliminary data from mice
He also talked that they started using this year “Aging rate indicators” (IL-6, CRP, CIT, etc)
I do think a combination of approaches is essential. I don’t think there will be a single silver bullet that will do everything that it is practical to do.
Hence things like exercise remain important. The problem as I see it is that putting in a full set of different interventions is really hard with a thing like WormBot, it can produce useful information, but we also need to be looking at combinatory approaches via biohacking (which we are doing anyway)
@KarlT There are probably many reasons why things go slow but I’m convinced we can push things forward in a faster and more efficient way. One reason that I think why the interest is very low in the business field is that it’s not possible to capitalize on it. So we need to rethink things on how we move things forward without relying on businesses. Government funding is also a very slow process but as a crowd we can do so much more for a small effort. Like the example I raised. 3000 people sponsor 100USD to Ora Biomedical and after that we have two revolutionary projects ongoing which will deliver results within months. That is the power of a community. We need to use this power in a good way and now we have a great opportunity to start working together all
@Neo Big thumbs up! It can be good to just explain the difference between the million molecular challenge and the Rapamycin Longevity Lab. I would say the million molecular challenge is about using the wormbot to do one million longevity intervention experiments within 5 years. Lots of important and revolutionary discoveries will be done thanks to this. I really hope we can do it faster than 5 years.
The community-driven Rapamycin Longevity Lab focuses on moving the field forward around Rapamycin and next-generation mTOR inhibitors. In the first revolutionary project we will get an indication what the combination of different drugs and later on natural compounds has on Rapamycin. In this project we will get data on what combination may be synergistic, additive, canceling or have detrimental longevity effects.
In the second revolutionary project we will screen for better mTOR inhibitors than Rapamycin.
Nobody has done as I said before anything close to the magnitude of what these projects will deliver in data. It’s a very small price for what huge return of data we will get back. So these two projects are something that just must be done. I will dedicate a lot of time and energy to this but I can not do this by myself so we need to do this together. All types of help are appreciated. It can be everything from simple things such as to just spread the word about the lab or to help out in project leading a project or connecting with organizations who can help out in funding etc.
In future the lab will work with other projects in other species and setting up human trials around Rapamycin. So the lab is not only about using the wormbot and partnering with Ora Biomedicals. We will partner with lots of different researchers, other labs and organizations to move the field forward in a much faster way
@PolishGentleman Yes, I know he has mentioned that they have made a discovery already which they are if I’m not totally wrong applying a patent on. I really like the study which you are thinking about. One thing that I have sketched on as a potential future project when we have the results from the combination of Rapamycin is to create a cocktail project. Little bit similar to the Aubrey de Gray study in mice but with compounds instead. So we pick the top candidates from the combination results and the ones that we think may have complementary effects. We should not for example choose Rapamycin and 4 glucose regulating compounds. After that we do 25 combinations with them. Like combining all 5 with each other. Alla four etc. Such a small project I could fund directly through my company. It would be super interesting to see the results of that
@RapAdmin If someone can check this with him that would be great. @DeStrider you have already had contact with Richard. Is it something you could check with him?
I certainly don’t know the answer. It just feels like longevity research is engaged in omphaloskepsis (navel gazing). Think about where Rapamycin came from. We should do more of that sort of exploration (digging in the dirt/ mud/ undersea muck) if we hope to find miracles. But I’m satisfied that effort is being made in multiple directions.
@PolishGentleman I have been sketching on a pipeline for around one year on how we could speed things up so that we get different data points in multiple species in a cost-effective and fast way and eventually up to human trials. It’s very interesting that you lift these different things up to increase the probability to get it to the ITP. There is also one possibility that we take the fast track in ITP without proposal and finance an ITP experiment directly. The cost for that is 450k.
When things calm down a little bit it would be very interesting to discuss the pipeline with you all and see how we could start implementing it in the Rapamycin Longevity Lab
@John_Hemming I fully agree that we need much more than just the wormbot. As I see these initial projects is that we are starting to set up an highly effective pipeline for getting out a longevity intervention to use in humans in a successful way. So these two initial projects are only mini projects on what will come from the lab. Biohacking and MN=1 to RCTs are things that will come. So step by step forward so that it does not get overwhelming. We need first success in the first projects before adding more projects in how we move things forward
@Joseph_Lavelle Love the navel gazing expression! Hopefully the wormbot can give lots of new insights then what we find in the navel
I found it interesting in the most recent Peter Attia podcast with Matt and David S., that Peter mentioned that he thought he and his contacts (he has many wealthy clientel who are very interesting in longevity), could probably fund more research into rapamycin and rapalogs, etc. Given his popularity, and reach, I think that Peter is in a great position to accelerate research and testing in this area. Given his comments in the podcast I think he’s aware of that and will hopefully act more aggressively in this area.