Karel1
#7
Am I wrong when I say that I only see relative new substances?
For me this implies no big safety record in humans and unlikely to be affordable for persons with a small budget.
Big pharma will walk away with the big money…
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@Curious For donation you can visit the page Rapamycin Longevity Labs Fundraising Campaign (mTOR inhibitors #1) – Ora Biomedical, Inc. and make the donation through Ora Biomedical’s website. You can also contact me if you want. Big thanks for considering helping out!
@John_Hemming This is a great question, John! If we look at the ITP (=Intervention Testing Program) setup then they start with looking at lifespan and if they find promising interventions that results in lifespan extension then they start a new project where they do deeper analysis around healthspan improvements. This way they can keep their experiments very cost-effective but one risk is of course that they miss out compounds that increase healthspan but not lifespan. I think that is one risk now in the beginning we need to take because the goal is to find compounds that both increase lifespan and healthspan and not just healthspan.
If we also look at rapamycin then it results in good life extension in multiple species. So it would be great if a new promising mTOR inhibitor, which is better than rapamycin, would be able to do the same but with better results. If we look at for example the dual PI3K/mTOR inhibitor GSK2126458 then it looks good in worms.
But we need to get great results also in at least flies and mice. The flies experiment will start very soon and the mice experiments will hopefully be approved next year by the ITP. If the lifespan data is better than rapamycin then I think this increases the chances that we may have found something that we need to study more and push eventually to clinical trials.
Curious question, what’s your view on the topic when it comes to finding a better mTOR inhibitor than rapamycin?
@Karel1 You are fully right that these initial studies are not intended as data for people to start directly prescribing or self-experimenting with these compounds. The experiments in this project will be done in worms and let’s say we find 10-50 compounds that are very interesting then we test them in other species like flies, mice etc. After that we can start taking steps into clinical trials. The goal with this project is to start moving the longevity needle and not just settle with the known compounds we have in the field. If we want to live very long and well then we really need to start exploring things outside the known and push the field forward. That is one key reason why this project is so important. To push things even further then if we look at Rapamycin Longevity Lab then we will focus on engineering combination therapies in which we use the next generation of mTOR inhibitor as a base ingredient in these longevity cocktails. Below is a rough roadmap on what my lab’s mission is. If this is possible to achieve no one knows but together with other people I will do what it takes to see how far we can reach.
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I wonder myself if a shorter half life would be better for humans. The difficulty really is that there are lots of questions
a) How effectively does it inhibit mTOR
b) What else does it do
Hence that leads to any questions of side effects. Much of what Rapamycin does both positively and negatively comes from inhibiting mTOR.
It may be that it doesnt have any other major mechanisms.
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It is sad that we don’t have answers to these basic questions. My guess which I more and more lean towards is that individualized protocols is most likely the best approach. I have tried to lift this up in some of the talks and interviews I have been giving. Because what is best depends on many factors and by creating some kind of way to find the sweet spot here in an easier way I think is the thing that will give the best effect. In some situations we don’t want to inhibit mTOR like after a surgery. So here it would be really great if we could have some kind of overall metrics which could give guidance. If I have started sketching on one and I’m working on an updated version. Will try to publish it soon. My guess is that if we would also use a similar overall metric in for example mice lifespan studies, but of course adapted to that species, then we would be able to extend lifespan even more than we do today with rapamycin. Because I don’t think for example that it’s optimal to take high doses of rapamycin when the mice are close to dying. It’s like a weak human is lying in a sick bed and that person doesn’t have a long time to live but despite that we continue to give rapamycin to that person. I’m skeptical if that is the right approach. If we are in a weak state then activating powerful catabolic processes is most likely not the best way to go. But this is just my guess and it would be very interesting to test this hypothesis out.
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I think the hard question is working out when you need to ensure mTOR is not inhibited. You are welcome to republish my results published on this forum from a single high dose.
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I’m in!
I am having a devil of a time getting a prescription so I am hoping I can generate some good karma in order to start taking it!!!
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@John_Hemming Can you provide a link to that post?
@Dreamdoc Really big thanks for the support! Have you looked at this page with different physicians around the world who prescribes rapamycin? Rapamycin Prescription, Doctors that Prescribe It
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Yes, I found it after my post.
I am a bit put off by the high costs charged by so many antiaging docs. It feels predatory.
But… I found 2 new sources to share.
Agelessrx.com is offering a simple and affordable monthly fee model for sirolimus among others.
And mobilecarehealth.com - a telemedicine company that I initially used for GLP1 meds, is preparing a sirolimus protocol. Their pricing seemed a bit high for the GLP.1s so I will be curious to see what they charge.
If they are doing a compounded version of rapamycin I would avoid it. There have been many problems with bioavailability of the compounded rapamycin efforts.
FYI they also offer generic sirolimus for $85 per month. They do require labs.
AgelessRx offers both the compounded and non-compounded (generic) forms.
Compounded form is more economical. We account for the reduced absorption by increasing the total dose.
I personally take compounded, 15 mg per week. My sirolimus levels are comparable to somebody taking 4 to 6mg of the generic.
I found that the generic 6MG per week was too strong for me caused side effects such as fatigue and canker sores. Probably because I’m taking other things like metformin, and I’m still in my 40s.
Clinically, I don’t have a strong preference on which one patients take. The generic form is more expensive, but is “tried and true”. But I’m confident enough in the compounding version that I take it myself
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Yes - sorry, I wasn’t clear there. I was referring to the other vendor that @Dreamdoc mentioned: MobileHealthcare.
Interesting paper on mTOR inhibitors as tested in c.elegans:
Characterization of Effects of mTOR Inhibitors on Aging in Caenorhabditis elegans
Pharmacological inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway with rapamycin can extend lifespan in several organisms. Although this includes the nematode Caenorhabditis elegans , effects in this species are relatively weak and sometimes difficult to reproduce. Here we test effects of drug dosage and timing of delivery to establish the upper limits of its capacity to extend life, and investigate drug effects on age-related pathology and causes of mortality. Liposome-mediated rapamycin treatment throughout adulthood showed a dose-dependent effect, causing a maximal 21.9% increase in mean lifespan, but shortening of lifespan at the highest dose, suggesting drug toxicity. Rapamycin treatment of larvae delayed development, weakly reduced fertility and modestly extended lifespan. By contrast, treatment initiated later in life robustly increased lifespan, even from Day 16 (or ~70 years in human terms). The rapalog temsirolimus extended lifespan similarly to rapamycin, but effects of everolimus were weaker. As in mouse, rapamycin had mixed effects on age-related pathologies, inhibiting one (uterine tumor growth) but not several others, suggesting a segmental antigeroid effect. These findings should usefully inform future experimental studies with rapamycin and rapalogs in C. elegans .
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Karel1
#22
https://mmabrasil.localizer.co/uploads/default/original/3X/2/6/26245078ffb07fd4dc54bcbe1364148c0eacfa86.png
@Krister_Kauppi can you explain why sirolimus shows a negative effect on both healthspan and lifespan in this table. My guess dose way too high???
Thanks
Started with Mobile today - after the lab work was done they sent along the scrip and I was able to order Rapacan from the Amazon pharmacy.
I start today. 
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Karel1
#24
Crowdfunding seems great if it is to test substances that are well known and not patentable.
The product/diet etc. should be affordable for at least 80% of the population.
This seems to be relatively news substances based on chemical modifications of known substances which will result in high cost patented drugs and extreme profits for the discoverers.
Why not issue shares and let everyone who invests benefit instead of just the persons that run a farm of C. Elegans worms on a disc. Some persons in this forum can easily spend 25 or 100K without even notice it… I want longer healthspan and lifespan for the masses!
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@Karel1 I have been in contact with different labs around that in some labs they see good benefits of rapamycin and in other ones none. The latest person I talked to this week was with the researcher David Gem and they have had challenges with getting rapamycin to work in worms. Also the ITP for worms CIPT had this issue. The company Epiterna and also other labs. In this clip Mitchell Lee, the CEO of Ora Biomedical, talks about why Rapamycin and other rapalogs are not working as expected. The problem is due to problems with crystallization on higher doses but I think there might be some way to get rapamycin to work. This is why I’m trying to figure out some way for it and talk to different labs.
It’s good that you lift up the investment opportunities and I have started to think more and more around this. One big problem with making this project an investment project is that there would not be any good incentives to make this data public. I feel it’s very important that we provide this basic data to the public. It can not be hidden. But one potential way that I may add as a bonus to this project is that depending on the amount people sponsor the bigger pre-investing amount they will have around these compounds when Rapamycin Longevity Lab starts to develop cocktails around these. For example, let’s say you sponsor 1000$ then you will be able to pre-invest $1000 before everyone else on each new cocktail that the Rapamycin Longevity Lab develops based on these compounds. What do you think about that?
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amuser
#26
The below leads one to believe all 600 are funded by 50K, when in fact it covers only a bit over half the cost.
Suggest updating that 601 to 300.
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