15 ms·

Rapamycin: The unlucky history of an anti-aging drug

robinsord 3y ago
[dead]
starchild_3001 3y ago
Many of us know and follow rapamycin's story. There are some Drs in USA who're willing to prescribe it for longevity. I do hope some billionare will be willing to spend a few million on it to test it in clinical trials. Surely one of the most promising molecules out there, and very little sides when dosed intermittently.
- kurthr 3y ago
  There are quite a few studies ongoing in '22 and '23. https://www.rapamycin.news/t/rapamycin-clinical-trial-update/2048 https://www.rapamycin.news/t/rapamycin-clinical-trial-update...
- cornholio 3y ago
  From the article, this molecule sounds like a big hammer that you can pound cell reproduction with, affecting a wide range of systems in unpredictable ways. Whereas what we need are precision watchmaker tools and a diagram of the watch. On thing I think is well established about aging is that it's not a single factor disease that you can "cure" by removing a well defined cause. Rather, it's a pervasive accumulation of entropy in various systems from various causes that evolution had no ability to correct, so that slowing aging down and reversing it involves a massive amount of tinkering with the watch.
  - tysam_and 3y ago
    It has so many immunity-related side effects IIRC. Lowering the drawbridge and opening the gate lets a lot of things happen/go in, both good and bad. I've heard that it's oftentimes a trade between two extremes, cancer or...well to be honest I've completely forgotten the second one. Huh.
  - amts 3y ago
    The anti-aging effects of rapamycin support the opposite of "pervasive accumulation of entropy" theory - which is that aging is a distorted development program, rather than random accumulation of entropy. The definition of "random" implies by default that lack of information or knowledge on the object in question is primarily due to cognitive (and hence measurement) limitations of its users, rather than something being 100% objectively ingrained in reality.
    - cornholio 3y ago
      Only chink in that theory is rapamycin doesn't seem to have anti-aging effects per-se, rather a wide array of systemic effects, some beneficial to longevity in special circumstances. In the general case, you definitely won't be extending lifespan of the elderly by modulating down their immune system or promoting amyloid formations. There is definitely "real" randomness, DNA replication errors are truly random because they are caused by quantum molecular effects. You can characterize them statistically and reduce their incidence, for example by controlling the diet or shielding the body from UV, but you can't measure those causes, only observe their effects. At best you could correct them, starting from a known-good-copy, as indeed cell biology already does.
schmichael 3y ago
Sorry for the meta-commentary but… HN’s anti-aging obsession is wild. I get zero anti-aging content from any other news source, user submitted or otherwise, and yet without fail it seems like there’s at least one anti-aging article a week on HN. Any other topic I find on HN I run into elsewhere: space, JavaScript, crypto, lisp, etc etc. Only on HN do I regularly see anti-aging “news” promoted. The discussions are all about the same: it’s a scam! It’s worth a shot! More research is needed! Anti-aging is unnatural! Anti-aging is a biological imperative! idk it must have fans to get so consistently upvoted, but I do not get the appeal.
- aaron695 3y ago
  [dead]
- db48x 3y ago
  https://www.youtube.com/watch?v=jdCB9yE9Hcc https://www.youtube.com/watch?v=jdCB9yE9Hcc
- xarope 3y ago
  There's a mindset amongst hackers that you can hack yourself, hence the popularity of life hacks, discussions of all sorts of drugs. I think it's up to each individual to decide whether they want to go that route and experiment with themselves or not...!
  - cornholio 3y ago
    It's a valid topic of discussion around here because people are educated enough to consider medical anti-aging as a plausible thing, whereas in other demographics you would be ridiculed as an idiot with a God delusion. But anti-aging in general is a topic permeating our entire society, from non-stop commercials to "rejuvenating" cosmetics and dead-sea-mineral-spas, to the boom of plastic surgery, to the fad diets promising a long healthy life, if we look around everybody talks about it one way or another because nobody wants to get old.
    - decremental 3y ago
34679 3y ago
There's a great Radiolab episode on this topic and the person who first isolated it. https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub
- stephenitis 3y ago
  I second this podcast, great vivid storytelling.
EdwardDiego 3y ago
The part where a compound first investigated as an antifungal improves longevity of fungi wasn't really explored, but eh? Is it controlling fungi that infect other fungi or something?
tysam_and 3y ago
Anti-aging is a hard problem, Rapamycin is most certainly not the most powerful anti-aging drug from my best understanding, it just targets 1 of 7 or 8 critical areas that are implicated in the aging formula. If you want to start down the rabbithole (SENS talks can be trusted and are good, well-backed by science, etc etc. Have been derailed by some drama recently, but still, they've really done a lot) then you can start by going to the rejuvenation roadmap: https://www.lifespan.io/road-maps/the-rejuvenation-roadmap/ https://www.lifespan.io/road-maps/the-rejuvenation-roadmap/ A little further (Aubrey de Grey, from SENS originally): https://www.ted.com/talks/aubrey_de_grey_a_roadmap_to_end_aging?language=tt https://www.ted.com/talks/aubrey_de_grey_a_roadmap_to_end_ag... If you want to lose 4-5+ hours (minimum -- think TVTropes level of rabbithole addiction here), then here is your next free joyride. It's a fun one, I've been pretty interested in it as it's continued to have developed. Have fun reading the saga: https://www.reddit.com/r/sleephackers/comments/ohfetn/turnbuckle_longecity_mitochondrial_fissionfusion/ https://www.reddit.com/r/sleephackers/comments/ohfetn/turnbu...
- Mistletoe 3y ago
  I can’t tell if this Turnbuckle protocol is going to be one of the most revolutionary things I’ve read or going to be like when Napoleon Dynamite puts on Uncle Rico’s time machine from the internet and shocks himself.
  - tysam_and 3y ago
    Likely if it works, it'll be one piece of the puzzle. It's not all that hard to try to be honest. Some people have reported absolutely massive changes, some small, some little to none. One or two said decrease but there seemed to be maybe some valid external factors for that. That's about the distribution one could expect if mitochondrial damage was at play and there was an effective solution for it. Not everyone is going to respond well, likely the older the better if it actually is doing what it says on the tin.
    - reducesuffering 3y ago
      That's about the distribution one could expect for placebo too.
snvzz 3y ago
Tangentially related: Fable of the Dragon-Tyrant[0]. 0. https://www.youtube.com/watch?v=cZYNADOHhVY https://www.youtube.com/watch?v=cZYNADOHhVY
- drBonkers 3y ago
  I didn't realize this short was first a textual story [1] until years after my first encounter. [1] https://nickbostrom.com/fable/dragon https://nickbostrom.com/fable/dragon
  - snvzz 3y ago
    Me neither. Thank you for bringing it to my attention. Today, I also learned about xianxia[0] from an unexpected place[1]. 0. https://en.wikipedia.org/wiki/Xianxia https://en.wikipedia.org/wiki/Xianxia 1. https://hsr.hoyoverse.com/ https://hsr.hoyoverse.com/
CapstanRoller 3y ago
Rapamycin is also being studied as a booster drug to ketamine for treatment-resistant depression https://www.bbrfoundation.org/content/surprising-clinical-trial-ketamines-antidepressant-effects-lasted-longer https://www.bbrfoundation.org/content/surprising-clinical-tr...
- cypherpunks01 3y ago
  Yes, my ketamine doctor actually suggested this last year and prescribed me rapamycin as a booster with ketamine infusion sessions, citing this study referenced. He's done this for some patients who don't get infusions frequently, to try and stretch the positive effects longer. It had a bit strange effects the first time I took the rapa, you dose it about 2 hours before ketamine infusion session. It actually attenuated the psychedelic effects of ketamine quite dramatically, which is interesting because the study predicted the rapamycin to strongly counteract certain effects of ketamine action, but the physical ketamine effects were still present for me. I did have the same positive mood boost starting later that day that I was used to with the infusions, I don't think the rapamycin hurt that effect and I was left with a good effect for some time afterwards. What I was left wondering is, is the rapamycin actually amplifying the ketamine mood boost, or does it simply have a separate antidepressant effect that you can layer on by co-administering it? I took the rapamycin a couple times outside of session, and it did seem to give me an antidepressant effect for a few days as far as I can tell, of course not in a controlled study environment. But internally, I concluded that ketamine and rapamycin both have antidepressant effects that can both be used to positive effect, together or separately.
mannyv 3y ago
Sounds like this would have been a great candidate for covid patients with immune system issues...like cytokine storms etc.

[dead]

Many of us know and follow rapamycin's story. There are some Drs in USA who're willing to prescribe it for longevity. I do hope some billionare will be willing to spend a few million on it to test it in clinical trials. Surely one of the most promising molecules out there, and very little sides when dosed intermittently.

kurthr 3y ago
There are quite a few studies ongoing in '22 and '23. https://www.rapamycin.news/t/rapamycin-clinical-trial-update/2048 https://www.rapamycin.news/t/rapamycin-clinical-trial-update...
cornholio 3y ago
From the article, this molecule sounds like a big hammer that you can pound cell reproduction with, affecting a wide range of systems in unpredictable ways. Whereas what we need are precision watchmaker tools and a diagram of the watch. On thing I think is well established about aging is that it's not a single factor disease that you can "cure" by removing a well defined cause. Rather, it's a pervasive accumulation of entropy in various systems from various causes that evolution had no ability to correct, so that slowing aging down and reversing it involves a massive amount of tinkering with the watch.
- tysam_and 3y ago
  It has so many immunity-related side effects IIRC. Lowering the drawbridge and opening the gate lets a lot of things happen/go in, both good and bad. I've heard that it's oftentimes a trade between two extremes, cancer or...well to be honest I've completely forgotten the second one. Huh.
- amts 3y ago
  The anti-aging effects of rapamycin support the opposite of "pervasive accumulation of entropy" theory - which is that aging is a distorted development program, rather than random accumulation of entropy. The definition of "random" implies by default that lack of information or knowledge on the object in question is primarily due to cognitive (and hence measurement) limitations of its users, rather than something being 100% objectively ingrained in reality.
  - cornholio 3y ago
    Only chink in that theory is rapamycin doesn't seem to have anti-aging effects per-se, rather a wide array of systemic effects, some beneficial to longevity in special circumstances. In the general case, you definitely won't be extending lifespan of the elderly by modulating down their immune system or promoting amyloid formations. There is definitely "real" randomness, DNA replication errors are truly random because they are caused by quantum molecular effects. You can characterize them statistically and reduce their incidence, for example by controlling the diet or shielding the body from UV, but you can't measure those causes, only observe their effects. At best you could correct them, starting from a known-good-copy, as indeed cell biology already does.

schmichael 3y ago

Sorry for the meta-commentary but… HN’s anti-aging obsession is wild. I get zero anti-aging content from any other news source, user submitted or otherwise, and yet without fail it seems like there’s at least one anti-aging article a week on HN. Any other topic I find on HN I run into elsewhere: space, JavaScript, crypto, lisp, etc etc. Only on HN do I regularly see anti-aging “news” promoted. The discussions are all about the same: it’s a scam! It’s worth a shot! More research is needed! Anti-aging is unnatural! Anti-aging is a biological imperative! idk it must have fans to get so consistently upvoted, but I do not get the appeal.

aaron695 3y ago
[dead]
db48x 3y ago
https://www.youtube.com/watch?v=jdCB9yE9Hcc https://www.youtube.com/watch?v=jdCB9yE9Hcc
xarope 3y ago
There's a mindset amongst hackers that you can hack yourself, hence the popularity of life hacks, discussions of all sorts of drugs. I think it's up to each individual to decide whether they want to go that route and experiment with themselves or not...!
- cornholio 3y ago
  It's a valid topic of discussion around here because people are educated enough to consider medical anti-aging as a plausible thing, whereas in other demographics you would be ridiculed as an idiot with a God delusion. But anti-aging in general is a topic permeating our entire society, from non-stop commercials to "rejuvenating" cosmetics and dead-sea-mineral-spas, to the boom of plastic surgery, to the fad diets promising a long healthy life, if we look around everybody talks about it one way or another because nobody wants to get old.
  - decremental 3y ago

34679 3y ago

There's a great Radiolab episode on this topic and the person who first isolated it. https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub

stephenitis 3y ago
I second this podcast, great vivid storytelling.

EdwardDiego 3y ago

The part where a compound first investigated as an antifungal improves longevity of fungi wasn't really explored, but eh? Is it controlling fungi that infect other fungi or something?

tysam_and 3y ago

Anti-aging is a hard problem, Rapamycin is most certainly not the most powerful anti-aging drug from my best understanding, it just targets 1 of 7 or 8 critical areas that are implicated in the aging formula. If you want to start down the rabbithole (SENS talks can be trusted and are good, well-backed by science, etc etc. Have been derailed by some drama recently, but still, they've really done a lot) then you can start by going to the rejuvenation roadmap: https://www.lifespan.io/road-maps/the-rejuvenation-roadmap/ https://www.lifespan.io/road-maps/the-rejuvenation-roadmap/ A little further (Aubrey de Grey, from SENS originally): https://www.ted.com/talks/aubrey_de_grey_a_roadmap_to_end_aging?language=tt https://www.ted.com/talks/aubrey_de_grey_a_roadmap_to_end_ag... If you want to lose 4-5+ hours (minimum -- think TVTropes level of rabbithole addiction here), then here is your next free joyride. It's a fun one, I've been pretty interested in it as it's continued to have developed. Have fun reading the saga: https://www.reddit.com/r/sleephackers/comments/ohfetn/turnbuckle_longecity_mitochondrial_fissionfusion/ https://www.reddit.com/r/sleephackers/comments/ohfetn/turnbu...

Mistletoe 3y ago
I can’t tell if this Turnbuckle protocol is going to be one of the most revolutionary things I’ve read or going to be like when Napoleon Dynamite puts on Uncle Rico’s time machine from the internet and shocks himself.
- tysam_and 3y ago
  Likely if it works, it'll be one piece of the puzzle. It's not all that hard to try to be honest. Some people have reported absolutely massive changes, some small, some little to none. One or two said decrease but there seemed to be maybe some valid external factors for that. That's about the distribution one could expect if mitochondrial damage was at play and there was an effective solution for it. Not everyone is going to respond well, likely the older the better if it actually is doing what it says on the tin.
  - reducesuffering 3y ago
    That's about the distribution one could expect for placebo too.

snvzz 3y ago

Tangentially related: Fable of the Dragon-Tyrant[0]. 0. https://www.youtube.com/watch?v=cZYNADOHhVY https://www.youtube.com/watch?v=cZYNADOHhVY

drBonkers 3y ago
I didn't realize this short was first a textual story [1] until years after my first encounter. [1] https://nickbostrom.com/fable/dragon https://nickbostrom.com/fable/dragon
- snvzz 3y ago
  Me neither. Thank you for bringing it to my attention. Today, I also learned about xianxia[0] from an unexpected place[1]. 0. https://en.wikipedia.org/wiki/Xianxia https://en.wikipedia.org/wiki/Xianxia 1. https://hsr.hoyoverse.com/ https://hsr.hoyoverse.com/

CapstanRoller 3y ago

Rapamycin is also being studied as a booster drug to ketamine for treatment-resistant depression https://www.bbrfoundation.org/content/surprising-clinical-trial-ketamines-antidepressant-effects-lasted-longer https://www.bbrfoundation.org/content/surprising-clinical-tr...

cypherpunks01 3y ago
Yes, my ketamine doctor actually suggested this last year and prescribed me rapamycin as a booster with ketamine infusion sessions, citing this study referenced. He's done this for some patients who don't get infusions frequently, to try and stretch the positive effects longer. It had a bit strange effects the first time I took the rapa, you dose it about 2 hours before ketamine infusion session. It actually attenuated the psychedelic effects of ketamine quite dramatically, which is interesting because the study predicted the rapamycin to strongly counteract certain effects of ketamine action, but the physical ketamine effects were still present for me. I did have the same positive mood boost starting later that day that I was used to with the infusions, I don't think the rapamycin hurt that effect and I was left with a good effect for some time afterwards. What I was left wondering is, is the rapamycin actually amplifying the ketamine mood boost, or does it simply have a separate antidepressant effect that you can layer on by co-administering it? I took the rapamycin a couple times outside of session, and it did seem to give me an antidepressant effect for a few days as far as I can tell, of course not in a controlled study environment. But internally, I concluded that ketamine and rapamycin both have antidepressant effects that can both be used to positive effect, together or separately.

mannyv 3y ago

Sounds like this would have been a great candidate for covid patients with immune system issues...like cytokine storms etc.