We’ve achieved 30% of our funding goal for the groundbreaking mTOR inhibitor screening project! The purpose with this project is to uncover even more potent mTOR inhibitors than Rapamycin when it comes to extending lifespan. If you’re enthusiastic about longevity or want to make a difference, please get in touch or help out in spreading the word around this project!
I’m happy to announce our first gold sponsor who is
Antoine Dusséaux: a London-based entrepreneur. Connect with him on X via @adssx or here on Rapamycin.news.
Other sponsors of the project are
AgelessRx: A cutting-edge telemedicine platform that specializes in making various longevity interventions accessible for people. The company is also actively involved in research and clinical trials around longevity interventions.
Una Health: The first digital longevity clinic in Sweden for biohackers and entrepreneurs. Focusing on primary prevention, early detection, health optimization and age inhibition.
OpenCures: A unique online platform that empowers individuals, health professionals, laboratories and researchers with the purpose to accelerate the development of longevity interventions.
Healthspan: The first-ever digital medical clinic to help patients fight cellular senescence and regain control over the levers of aging that are at the foundation of most age-related chronic diseases.
Rapamycin Longevity Lab: The mission is to become the leading experts in combinational longevity therapies in which we use a mTOR inhibitor as a base.
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@Joseph_Lavelle Yes, really big thanks to @adssx! I have a good feeling that we will get valuable data from this project to push the field forward. It’s just a bit frustrating that it takes time to get the project funded. I will do what I can to accelerate it. The white paper around the project will soon be completed and ready for sending out to potential funders. I will also visit the biggest longevity conference ARDD now in August and put up a project poster on that event. So step by step forward.
@Neo I have plans to release a sponsoring tier for 50-100$. It will create a little bit more work to administrate that but it’s worth it. I have started some discussions with Ora Biomedical around how to solve it in a good way. Big thanks for wanting to help!
You should work with leaf or longevity.io since they already provide a 5013c tax deductible way to contribute to ora biomedical. Would be easy for them to add one more button to the options
@Josh Ah, interesting! I did not know about the 5013c tax deductible. Where can I read more about that? I have a plan to ask them if they want to highlight the project in an article but it would also be interesting to combine it with a donation support. Great feedback!
@KarlT It’s direct and indirect mTOR inhibitors. I’m currently creating a white paper where all these will be listed. But I think the image below shows roughly some of the pathways to inhibit mTOR.
The Rapamycin Longevity Lab discovered recently this year for example the PI3K/mTOR inhibitor GSK2126458 as a interesting compound. Another lab here in Europe has also reproduced the results multiple times. It would be very interesting to see if we can achieve even greater effects with other mTOR inhibitors. Even if we don’t I think the value of this data will be very important. Let’s say that we find out that compound X leads to a decrease in lifespan then from a clinical therapeutic perspective I think it’s important for pharma to look at this so that they offer people things that don’t at least decrease lifespan.
@John_Hemming Interesting, can you elaborate more on why you think that may have a better longevity effect? Any interesting studies around that?
The reason why I think a shorter half life would be helpful is that we don’t IMO want to inhibit mTOR all the time. In fact I think we want mTOR to function normally most of the time.
I agree that we don’t want to shut down mTOR because then we would be dead but I think things point towards that turning down anabolic processes to a level that is not detrimental is probably good. The lower the better but it’s also very easy to go too far and overexpress catabolic processes too much. So it’s about finding the sweet spot here and that sweet spot is constantly fluctuating.
Last year I started sketching roughly on the image below and measurements on how to potentially find the sweet spot. This is of course just speculation that these measurements are the thing to use but I like the idea of getting something to use when navigating in this longevity jungle. If you have any suggestion on more measurements please let me know Fragile index and bone density are for example things I will add to it. Maybe also iron and testosterone levels.
The thing that I would like to see is in what cases we want to activate anabolic processes more. Wound and fracture healing is one thing. After exercise is another thing but I think here we also have a sweet spot around athletic performance. I would argue that more is not necessarily better and that the sweet spot is a bit above where we can keep functional performance up around daily todos and avoid being fragile and weak. But I don’t think we need to be very strong and muscular etc. But it depends a lot what type of life goals a person has. Here is a quite interesting model that I created recently.
The times are when I want my body to be able to renew (bones, muscles, kidney function, etc etc). As inhibiting mTOR holds back cell division I want to avoid that. Hence I wish mTOR to function normally the majority of the time, but to have increased autophagy every so often to improve mitochondrial quality. My most recent experiment was to take 16mg of Rapamycin combined with a grape fruit, but at a lower frequency than my previous 21 days for 6mg plus accelerator. I expect Rapamycin to disrupt sleep and the sleep disruption appeared to last perhaps just over a week.
The problem is measuring mitochondrial efficiency. I think it might be possible to measure this on a fasting basis without citrate supplementation with the level of serum citrate, but that is harder to get measured and I don’t know what daily cycles it may go in.
“I wish mTOR to function normally the majority of the time”
The normal seems to be that the mTOR activation is more often on a high level thoughout the day when the organism get older. I talk a little bit about this in this time clip.
So I don’t think normal is something to strive for here. It’s probably better to strive for youthful activation levels. Maybe it was that you meant instead of normal?
The question really is how best to active optimal autophagy. We know the body is in a state of renewal. I don’t myself think mTOR is at the core of the aging process. I think it is about gene expression. However, if mTOR is always active then this discourages autophagy.
I was running with 6m +GFG every 21 days, but I am now juggling up whether to stick moreso with 16mg + GFG or even more, but perhaps every 2 months.
At the moment I am away from my main base so I cannot properly monitor the hair follicles that are useful as a visible representation of cellular function that shift within a few days of making a systemic change. I have, however, had two blood test results.
However, they are not as broad as the test I will do next wednesday.
It would really help out to have some kind of CGM but for mTOR but even if we could measure it we don’t yet know how to optimally finetune it. But until then I hope that both of our protocols work.
I think we know from the individual experimentation that people have done on this forum that there are limits on weekly dosing and people can get negative results from too much Rapamycin.
What is unclear is whether taking larger doses less frequently is an improvement on smaller doses more frequently or not.
I manage my health in the round measuring lots of things and making lots of detailed changes.
I have a mechanistic hypothesis which makes this sort of approach less scattergun than it would otherwise be, but my hypothesis may be wrong.
In the end, however, mechanistically there does need to be at least some idea of an optimal answer. There are arguments from some against the less frequent dosing, but I have not seen evidence for that.
Antoine Dusséaux: a London-based entrepreneur. Connect with him on X via @adssx or here on Rapamycin.news.
