🧬🛍 19 - The Case for Rapamycin
Hello 👋 and welcome to Curation for Longevity by Laura Minquini. I am the founder of MYKIGAI - a discovery and recommendation platform for longevity.
In this newsletter, I look into what could help make longevity the next big consumer health & lifestyle category. 🚀
At the SALT conference last year, Dr. Jennifer Garrison, the Co-Founder & Director of the Global Consortium for Reproductive Longevity & Equality, declared that “if we can figure out what causes ovarian aging, this is going to give us clues for the rest of the body ages”, and thus have a serious breakthrough in healthy longevity.
If you have read this newsletter you know that the yet-to-be-released final trend of the Longevity forecast for 2022 is focused on this subject. In the method to my madness, I am very excited to announce an upcoming panel with VitaDAO alongside other amazing female founders and scientists in the field.
Exploring longevity from a female perspective is crucial not only because it could lead to outcomes that are beneficial for all, but because it makes business sense when you remember that women make 90% of the health decision in households. Please join us!
DATE/TIME: Thursday, 7th April / 12 PM PST / 3 PM ET
ON: Twitter Spaces 🔗 LINK HERE
One short and long term bet on Longevity 🎲🧬
Whatever your inclinations are, please don’t believe anyone who tells you they can make you or your dog immortal. A recent Netflix docuseries chronicles the downfall of a famous NYC vegan chef who, having been promised amongst other things, immortality for her and her dog, siphoned nearly $2 million out of her restaurant to give to a man who claimed to hold the key to eternal life.
Unfortunately, we are far from it, and as my longevity maximalist friend Kai Micah Mills says: “Immortality will happen, but it won’t be pretty”. More on that in next week’s post.
So, let’s pretend that I’m entering the casino that the web3 world feels like these days and place my bets!
Short term on Rapamycin, long term on Cryonics.
The case for Rapamycin 🗿🧬
Highlights:
Rapamycin: The Viagra of Longevity
A brief history of the drug that was almost left undiscovered
Key longevity scientists - so far
Reasons it is worth thinking of for longevity
Resources and ongoing trials
Why bet on it
My personal bet
Rapamycin: the Viagra of Longevity
Instead of keeping your hard-on going, Rapamycin is like Viagra in that both these drugs have unintended use. Originally developed to treat cardiovascular problems, we now know what Viagra is famous for. How ironic that the Erectile Disruption it helps, is a byproduct of aging.
Rapamycin is like Viagra because for now, it’s officially an immunosuppressant for transplants, but it might end up being the closest we get to an “anti-aging” drug this decade. Better than a hard-on!
A brief history of the drug that was almost left undiscovered
For as long as we discuss Rapamycin, I will always find an occasion to remind everyone that it was the discovery of a Canadian scientific team. Yay Canada!
“On a cold November day in 1964, a team of about 40 doctors and scientists boarded the Royal Canadian Navy’s H.M.C.S. Cape Scott in Halifax, Nova Scotia. They were headed to Easter Island, a triangle-shaped speck in the South Pacific that’s 2,200 km from its nearest inhabited neighbor.” The Chileans were at the cusp of disturbing their isolation with an airstrip.
The University of Montreal microbiologist Georges Nógrády - one of the instigators of this excursion -was not looking for cures, but we might end up owing him a lot in that realm.
As the story goes, he was trying to understand why the islanders who walked barefoot did not pick up tetanus, a bacterial infection found in places with horses, of which there were a lot.
Obviously, there was something to the soil.
The research might have ended up there except it was passed to Ayerst Pharmaceutical in 1969. After two years, they had found a new natural product. They called it rapamycin, after Rapa Nui, the name given to Easter Island by its indigenous people.
The work stopped in 1982. Had it not been for Suren Sehgal, a Microbiologist who was convinced that this material was “extremely valuable for saving human lives”, our use of rapamycin may not exist today. He packed the bacterium into vials, took them home, put them in the fridge with a sign on them saying “Do not eat”. Thank you Dr. Sehgal and to the family for not eating it!
With Rapamycin’s antifungal activity, they discovered that the compound was not only a potent immunosuppressant but could also keep cells from multiplying. You can read the complete amazing story HERE.
In 1999, the FDA approved the molecule as the drug Rapamune (sirolimus), also known as rapamycin. Its intended use was as an immunosuppressant to prevent organ transplant rejection.
By the mid-2000s, rapamycin was found to increase the life span of worms and yeast, and in a 2009 study, it extended the life expectancy of mice by 28 percent for males and 38 percent for females.
So starts the story of longevity.
Key longevity scientists in the history of research - so far
I wanted to do a cool collage of everyone but the best photo I found was of Dr. Kaeberlein looking like Captain America with his dog Dobby. I have joked with him that he will be the Jesus of many people if his study with dogs and Rapamycin does extend their healthy lifespan. Alas, to not be biased, no photos!
Reasons it is worth thinking of for longevity
Taken from a presentation by Dr. Kaeberlain:
Why mTOR matters:
What is mTOR?
“Great for muscle, bad for cancer”. Was an interesting description I found.
When mTOR is activated, it triggers muscle hypertrophy (an increase in muscle size) through an increase in protein synthesis (how your body turns protein into muscle tissue). Basically, when mTOR is on, it helps you build muscle. But you can go overboard.
There's evidence that both too much mTOR activity and too little mTOR activity is a problem and it happens in different diseases.
For example, too much mTOR activity is clearly connected to certain types of cancers and neurological diseases, particularly epilepsy and there's some evidence even for autism. Too little mTOR activity is connected to diseases such as atrophy of the muscle in certain situations, even aging a certain cell.
mTOR is basically like champagne. You have a glass and you feel sexy and giddy, you have a bottle, and you are ruined for days. You want some, but not too much of it.
Resources and ongoing trials
COMMUNITY 👥
🔗 Rapamycin News News + Discussion Forum. You can meet other people experimenting with Rapa (that is how users call it) as well as share your journey and outcomes. One of the co-founders has been giving rapa to one of his chickens, and it is laying eggs again! (International)
REGISTRY 🗂
🔗 Rapamycin Human Longevity Open Registry A worldwide initiative to collect data on individuals using rapamycin for longevity through a series of online surveys. (International)
CURRENT STUDIES/ TRIALS 🔬
🔗 University of Washington Rapamycin Study To assess the impact of Rapamycin use on healthy people and disseminate these findings for the benefit of everyone. (International)
🔗 PEARL (Participatory Evaluation of Aging with Rapamycin for Longevity) Trial This is a double-blind, randomized, placebo-controlled trial. Notably, it is the first nationwide telemedicine trial and the first large-scale intervention trial on longevity. (USA only)
BEST KNOWN MD PROVIDING THERAPY 👨⚕️
🔗 Dr. Alan Green (USA)
DOG STUDY 🐶
🔗 Dog Aging Project TRIAD (Test of Rapamycin in Aging Dogs) Through the NIA (National Institute of Aging) - supported Dog Aging Project (DAP), scientists aim to understand how a complex combination of genes, lifestyle, and environment influence aging not only for dogs but for humans as well. They will also be looking at the effect of dogs taking rapamycin. (USA only)
I threw in the NIA reference as I found funny what google shows “people also ask” when it comes to rapamycin and dogs. It is illuminating.
Note: Rapamycin, like any medicine, has side effects. I am not going on extensively on the potential downside, because I am making the case for it, but taking it as a longevity drug is at your own risk. This is the reason trials and surveys are being conducted: to measure efficacy and to see the side-effects on healthy adults.
Why bet on Rapamycin 💸
Aside from the trials and growing interest, I can pinpoint two market signals on its short term potential:
Last year, Unity Biotechnology’s co-founder Nathaniel David declared at the Salt conference (yes, it was a good conference) that the only significant development that will probably happen in longevity the next decade is the “micro-dosing of Rapamycin”. The guy has been in the industry for a while, one would think he knows a thing or two.
I think James Peyer might have been taking notes while in the same panel. Just last month, fresh from a $100 million Series C round, the CEO of Cambrian Biopharma, (the company “building the medicines that will redefine healthcare in the 21st century – therapeutics to lengthen healthspan,”) licensed Rapamycin from Novartis.
“The licensed assets are structural analogs of the FDA-approved drug rapamycin, which has been shown to prevent or reverse multiple age-related health deficits in mice1 and extend their average lifespan by up to 31%2.”
I mean, one does not have to be a genius to think Rapamycin is going to be important if you simply “follow the money”.
Dr. Kaeberlein pointed out recently on a webinar that the reason it’s not looked into as much is that it is a drug that is already off-patent, aka a generic drug. The upside in research is not the same as looking for the next new pill.
However, I could get “shrooms'' from any dealer at a party back in the day for $10. Now there is a massive psychedelics industry and I promise you it’s not that price anymore to micro-dose “psilocybin”; the grown-up, and official name.
I have no doubt the wheels of capitalism will figure it out.
My personal bet
Remember, the study that showed that Rapamycin extended the life expectancy of mice by 28 percent for males and 38 percent for females.
Twenty-eight percent could translate into more than a decade of better years for humans. Note that I am speaking of the percentage mentioned for men.
I asked multiple times on Twitter and around if there were women openly speaking about their use of Rapamycin or fertility impact as one of its potential uses might be the increasing ovarian lifespan. (Please see studies below).
Nada. Rapamycin and all the voices going gung-ho about it, were as usual: les garçons.
I find myself in a unique position between the years past my optimal fertility and close to the start of the end of it. So I have decided to only talk the talk but walk the walk and am taking rapamycin. Yay, I am finally becoming a real biohacker.
I am going to focus on documenting the effects it will have on my fertility, to see if I can put off perimenopause and menopause until more options exist to avoid the symptoms and accelerated rate of aging.
Remember I have written about how menopause accelerates women’s cellular aging and our ovaries age 2.5 faster than our body? Yeah…that’s one journey I am not into.
Maybe I could even pull off a Naomi Campbell and have my biological baby at 50! What I know is that like Naomi, and on a suggestion by Dr. Robert Lufkin when he interviewed me, I might be writing a book on the experience.
Potential titles:
“Forget crystals and patchouli for midlife, give me the Rapa!’’
“Midlife is quarter-life with Rapa”
“Midlife is definitely not a crisis, because I take Rapa”
Ok, those titles are jokes, but you get the idea.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506398/
https://academic.oup.com/biomedgerontology/article/76/9/1551/5893770?login=false
Longevity ToolKit: Hormones
Please remember to check our Longevity ToolKit, and Longevity Drop. We are adding posts weekly without sending you emails as to not spam you! This month as we look at longevity + fertility. It makes sense to take a close look at hormones.
🔗 Optimizing your Hormonal Health, Part 2: Oxytocin
Next week: Cryonics has become plan A
When some of the biggest names in the industry, and the new wave of founders like Kai, go into this area, the signalling is clear, cryonics is plan A.
To be continued…