I’m very proud today because this is the launch of the Rapamycin Longevity Lab. At the same time I’m also concerned because I have started to see more and more friends and relatives that are getting older, sicker, more fragile and some even have died way too young. One of the biggest risk factors for all these things and age-related diseases is aging.
The purpose of different longevity interventions is to target aging and by this slow the aging process down so that we can keep our health and quality of life up throughout our lives. One of the most promising longevity interventions is Rapamycin which research has shown good longevity effects in multiple species and with results that are quite easy to reproduce. This is unique when it comes to longevity interventions. In the near future we will also start to get more interesting data on how it works on humans.
But I get very frustrated that the longevity research around this goes way too slow forward. One reason for this is that there is no longer a valid patent for Rapamycin and this makes it hard to capitalize on the substance. My philanthropic personality just can’t accept this situation so my goal is to together with other people start to move this research field forward and make a difference. This is why I have started this community-driven Rapamycin Longevity Lab and everyone can join it for free. Let’s start to move the needle together and start the two revolutionary longevity projects around Rapamycin which are lifted up on the homepage.
I know Matt Kaeberlein said once that for 5 million $ he could test 1 million interventions - it would mean 5 $ per intervention. Would price per intervention drop with higher amount of funding?
For example, with, 200 000 $ could it lead to more like 10 000 tested interventions instead of 2 000?
I talked last week with Matt Kaeberlein about discounts in future projects if things really take off so there is most likely a potential to get this later on. Thanks to the partnership that the Rapamycin Longevity Lab has with Ora we will get lots of free very valuable coaching and help from them in our different projects. I also see Matt as an important key person to have with us when we build this lab to something big in the Rapamycin area. He has lots of good contacts, good knowledge about multiple species, credibility in the field, a big passion in the field etc. By the way, it would be very nice to also get in other big passionate and knowledgeable key persons to the lab. Like Peter Attia. I think for example he could contribute with lots of value to the lab and move things forward in a much faster way. I will see what I can do here. Will talk to Matt about this
This is an interesting new paper that applies to Wormbot and Longevity Lab… it seems that strain of worm (c.elegans) matters, and also touches upon the issue I’ve heard from c.elegans researchers that rapamycin is really hard to get uptaken (bioavailability?) in many strains of c.elegans, and so doesn’t necessarily represent well in this model organism…
Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes
We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies—for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.
It looks like Rapamycin and Acarbose didn’t work there, we don’t know why it didn’t work - may be related to
Bioavailability
Dose tested (too low or too high)
Rapamycin may not extend lifespan in all animals - maybe some animals have lower basic mTor levels or maybe mTor lowering isn’t beneficial in all animals
But paper also shows great difference based on background - for example green tea extends massively lifespan of C Elegans but shortens life of C Briggsae
They tested a dose 2x lower than what Robida-Stubbs reported to increase lifespan in worms. It’s not surprising that if you test a dose below the effective concentration the experiment won’t work. They probably did this because the 100 uM amount that extends lifespan in worms is also near the threshold of precipitating out of the media and they couldn’t figure out how to make it work in their system.
One way around the solubility issue is to use a genetic model sensitized to mTOR inhibition. The rsks-1 knockout is deficient in S6 kinase, which is downstream of mTOR. I’ve been encouraging @Krister_Kauppi and the guys at Ora to screen across the rsks-1 mutant to identify drugs that synergize with rapamycin.
A couple of other things to consider about this CITP paper.
(1) Failure to increase lifespan at a single dose tested means nothing. As in the case of rapamycin in this study, if you pick the wrong dose you will get a false negative Type II error.
(2) If the NIA had invested what they’ve spent on the CITP into the Ora Biomedical Sponsor the MMC project, we’d have a publicly available database of more than 250,000 interventions. How many has the CITP published? Guessing it’s less than 50. Why isn’t their data publicly available?
Hi Matt
I didn’t know that you are browsing this forum
Is there any web database / web page where we could find data from experiments from Wormbot / Million Molecule Challenge?
@mkaeberlein if you are the real Matt Koeberlein we are honored to have you contribute on these boards. Will continue to follow you and your work. Thanks,
I don’t get on here much, but was pointed toward this discussion. I’ll try to drop in more frequently.
The Ora open access database will become available when the first sponsored experiments are completed. I believe their target is early Jan for the first release. Unless people opt out, all data from sponsored experiments will go into the public database, so hopefully there will be enough support from the community to make it a big one.
Dr Kaeberlein, he’s awesome. He did the dog aging project which my dog Kamela is a member of. Dog aging project gave dogs Rapamycin, which is very interesting.
Unfortunately, my miniature pincher was too small to take part in the Rapamycin study. She still a member. The dog aging project used larger dogs for the project.
BTW, do we have any data from this or other research yet?
From what I know, Matt Kaeberlein said 2 months ago that they plan to release a longevity database in January 2024 with community sponsored drugs on C Elegans from Wormbot - but I don’t know if it exists yet
Yes, we are honored to have him here.