Rapamycin, drug used in cancer therapy, emerges as powerful anti-aging remedy

https://www.age.mpg.de/communications/news/detail/times-arrow

by cwwc • 4 years ago

192 219 4 years ago

age.mpg.de

mod2• 4 years ago

There was an in depth discussion about this drug with a longevity researcher on a recent episode of the Tim Ferriss podcast, in case anyone wants to dive deeper.

sndean• 4 years ago

a longevity researcher

Probably Peter Attia?

There's also some free to read review articles (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/). No idea about the quality of the journal Aging or the field in general, though.

mod2• 4 years ago

No, Matt Kaeberlein-- here's the transcript of the episode.

https://tim.blog/2022/07/30/matt-kaeberlein-life-extension-t...

theplumber• 4 years ago

This part sounds familiar: "One step closer to applications"

jjallen• 4 years ago

I know and agree with this sentiment.

However, you can take Rapamycin now. It is an existing drug.

w10-13• 4 years ago

"you can take Rapamycin now. It is an existing drug"

No: your doctor can prescribe it for you if it's indicated, or when there's good evidence that you need what it can do more than the side effects you'll suffer.

It's just like a gun: useful in some situations. But unlike guns, it's not you who decides.

orangepurple11• 4 years ago

The bigger story with rapamycin is that the mechanistic target of rapamycin (mTOR) plays an absolutely crucial role in major diseases of modern civilization. One of the ways to inhibit mTOR for free is to simply stop consuming nutrients for extended periods of time.

Tepix• 4 years ago

... to simply stop consuming nutrients for extended periods of time

That is not simple for most people.

chrisweekly• 4 years ago

simple != easy

bitxbitxbitcoin• 4 years ago

I think they meant fasting.

mrandish• 4 years ago

True but after I went very low-carb, I found fasting to be much easier when it had always been very hard for me previously. I know it's more complicated than "carbs cause hunger pangs ~8 hrs later" but my N=1 experience sure feels that way.

bitwize• 4 years ago

This is Hackernews. The cure is fasting. Whatever disease you have, the cure is fasting.

chaostheory• 4 years ago

It’s simple, but not easy. Intermittent fasting is an easier way to start compared to traditional fasting. Imo it’s still better than other diets due to its simplicity.

nils-m-holm• 4 years ago

One of the ways to inhibit mTOR for free to simply stop consuming nutrients for extended periods of time.

What is an extended period of time in this context? I happen to consume all my meals within seven hours every day and only drink water in between. Would that help?

(Not doing this for health reasons, it is just a habit.)

forgotmypw172• 4 years ago

A good measure is whether or not you feel that empty, churning feeling in your stomach. Another good measure is if you're into the idea of eating something like plain cabbage or oats.

rngname22• 4 years ago

https://podcastnotes.org/high-intensity-health/attia-7/

Around day 3 or day 4 of a water-only fast or (the potentially easier but still effective option of) of a fasting-mimicking diet fast.

nik_s2• 4 years ago

This [1] study was pretty thorough on different fasting lengths. They tested 1422 patients for fasting lengths between 4 and 21 days, with a maximum calorie consumption of 200-250kcal and a moderate-intensity lifestyle program.

It concludes that all fasting lengths are beneficial, and are likely going to result in a) reduction in weight and waist circumference, b) beneficial effects on blood lipids, regulation of sugar and other blood-related parameters, including lower blood sugars and higher ketone body levels, c) an increase in physical and emotional well-being and absence of hunger, d) a high probability of decrease of pre-existing health-complaints, e) very limited chance of side-effects.

[1] https://journals.plos.org/plosone/article?id=10.1371/journal...

simonebrunozzi• 4 years ago

Not an expert by any means, but based on some sparse reading I'd guess it's in the "few days" range, not a few hours.

JumpCrisscross4• 4 years ago

ways to inhibit mTOR for free to simply stop consuming nutrients for extended periods of time

How frequently and for how long must one fast to see this?

orangepurple11• 4 years ago

As long as you can bear it. Which for me has been 24 +/- 4 hours between meals for 9 months and counting.

CrispCas13• 4 years ago

As added information: metformin, a common anti-diabetic drug, is a inhibitor of mTOR. It potential adverse effects are less severe than rapamycin but are still significant. Specifically, long term usage can cause renal damage. Its mechanism of action has yet to be fully elucidated.

deltasevennine• 4 years ago

Can you source this? I believe you and I wanted to look into it. I googled this and I did not find anything explicitly saying renal damage. I did find many articles saying it's not safe to take if you already have renal disease but nothing saying that it causes it.

I even found articles that says it doesn't cause renal failure. I'm sure what you said is some real study just not popularized yet.

wobbleblob2• 4 years ago

Ages ago, I had a colleague who was deeply into hacking of his mTOR pathway. Among other things, this included a permanent calorie deficit and removal of all protein from his diet.

I don't know if he's still alive. Maybe it was working a bit too well, I recall he looked like an extremely tall 13 year old with anorexia.

LorenPechtel5• 4 years ago

You can't synthesize some of the amino acids. I wouldn't think such a diet is survivable.

meremortals2• 4 years ago

How does one find a doctor willing to prescribe these kinds of drugs for anti aging?

aaaaaaaaaaab3• 4 years ago

Pool your money with others and order in bulk from Asian or Sourh American suppliers. No questions asked. There are specific subreddits/forums for this kind of stuff.

jmhyer123• 4 years ago

Could you point me to some of those subreddits/forums? A quick search didn't yield anything but I'm probably not familiar with the specific terminology they would use.

nik_s2• 4 years ago

You can order these drugs in bulk from chemical vendors for research purposes (i.e. non-human use). Chemscene, to name just one, sells Rapamacyn at 1440 USD for 5g.

EDIT: I clearly don't recommend you buying this and taking it by the way. You're never quite sure about the purity nor about how to dose this effectively as a layperson without access to a lab. It's also possibly completely illegal, depending on your local laws.

LorenPechtel5• 4 years ago

Yeah. By the time you're looking at stuff in the milligram range it becomes quite problematic to ensure consistent doses. I would be confident that I could get an *average* of 1mg/day but I would not be confident I could ensure every day was in .9mg to 1.1mg.

orangepurple11• 4 years ago

The easiest way by safely and strongly inhibit mTOR is to simply stop eating for a while. Most people don't need the drug.

dylan604• 4 years ago

you've stated this multiple times in this thread, yet it's ambiguous at most.

if you mean fasting, say that. "stop eating for a while" to most people would be skipping lunch.

your drive by non-chalant "stop eating" / "stop eating nutrients" is just not helpful commenting the way you are

sinenomine• 4 years ago

I'm not taking Rapamycin due to costs and immune system concerns, but when researching this niche (specifically, I'm interested in senolytics) I have found this forum with this list of doctors https://age-reversal.net/physician-directory/

Maybe it could help you.

meremortals2• 4 years ago

Very helpful. Thank you

swader999• 4 years ago

Fisetin is compelling.

swayvil4• 4 years ago

What's the latest on bloodboys?

That is : periodic blood transfusion from healthy young vegan donor.

It works very well. Rejuvenates ancient billionaires.

Surely it's superpopular among the oligarchs. Probably not the kind of thing you want in the news (vampires!).

The technical term is Parabiosis.

These guys offer the service : https://www.ambrosiaplasma.com/

isoprophlex2• 4 years ago

Every day we stray further from god's light

chimen2• 4 years ago

[1] - "The figures are staggering: out of 35,000 children in care, more than 2,000 were physically or sexually abused by priests between 1936 and 1999" (Ireland alone)

[2] - French Church abuse: 216,000 children were victims of clergy - inquiry

1. https://www.justiceinfo.net/en/45133-sexual-abuse-church-map...

2. https://www.bbc.com/news/world-europe-58801183

swayvil4• 4 years ago

As evil goes it's pretty mild.

It could be much worse. The bloodboy might pursue a career in advertising.

moffkalast2• 4 years ago

Gavin Belson approved.

mtlmtlmtlmtl• 4 years ago

It's so strange to me that is is legal in the US when prostitution isn't(in most states).

Not that I think prostitution should be illegal, but it's basically the same thing.

4gotunameagain• 4 years ago

You are talking about a country that you can drive when you are 16 but drink when you are 21, and buy a rifle but not a kinder egg.

deegles3• 4 years ago

My understanding is that simple plasma dilution (plasmapheresis) has the same or better results. Though some of the sources I saw said that a centrifugal plasmapheresis machine is better than the membrane-based machines.

telesilla• 4 years ago

The article states effectiveness requires taking the drug as a young adult, precisely the time most people are not thinking about mortality.

lbotos• 4 years ago

I’d beg to differ. In the modern social media age youths are getting a lot more vain.

Teen boys are doing skincare routines.

So historically, I’d agree, but now that everyone can be a minor celeb in their own circle I think the youth are more focused on aging.

noneeeed• 4 years ago

Teen boys are doing skincare routines.

For context, there have been other periods in history when young men were as focused on their apperance as women, used makeup and obsessed about how they were seen.

Social media gives an outlet for this to those who are not wealthy, but none of it is fundamentally new, it was just confined to those who were able to do it.

yamtaddle2• 4 years ago

Teen boys are doing skincare routines.

Maybe, but I'd be careful about generalizing that kind of thing. Even stuff like consistently applying sunscreen is heavily dependent on class membership, i.e. it's "just what you do, obviously, any time you're going to be outside at all, of course we always have sunscreen on-hand and our kids have been taught to apply it as routinely and consistently as tooth-brushing—wait, why are you asking, doesn't everyone do that?" in some circles, while in other (larger) circles they only break it out for beach or lake days, if at all.

I expect the described behavior is similarly unevenly distributed.

junon• 4 years ago

I'm not even 30 yet and I'm already thinking about my mortality.

boredemployee3• 4 years ago

genuine question: why would someone want to live longer than the average?

Edit: I ask because I personally don't see a reason to stay alive while people I love are dying, I don't see a reason to stay alive in an already fucked up planet, while we empty all the resources, etc. But you guys are so smart, intelligent and clever, why even bother.

CalRobert2• 4 years ago

More time to do the things you enjoy.

sph• 4 years ago

More time to be a productive member of society, you mean.

ryeights• 4 years ago

Who wouldn’t want to be healthier than average at a given age?

wolfram74• 4 years ago

Curiosity? See where this ride is going and maybe have some hand however small to steer it?

deeel• 4 years ago

It's not only "living longer" as a whole organism, but also your individual organs living longer (that ultimately impact aging). Take ovaries for example: Menopause causes major health problems (osteoporosis, cardiovascular disease, etc) for women and women now spend on average more time post-menopause than pre. There's a good writeup about this problem and the companies researching it here: https://spannr.com/articles/oviva-therapeutics-raises-11-5m-...

boredemployee3• 4 years ago

that's a nice catch, thanks!

sunjieming• 4 years ago

This isn't just about extending how long you live but also the reduction of disease. That's something that seems highly promising about some of these treatments

orangepurple11• 4 years ago

It's generally not maximizing lifespan people are interested in but rather maximizing health span which is the period of time you are healthy and able to operate at a high level. If done correctly you die with minimum time spent disabled.

kiba• 4 years ago

If you max health span, you're going to live longer.

If you die, you're probably not healthy to begin with, or you die to very sudden trauma.

abletonlive• 4 years ago

It's funny to me that there is always someone that predictably asks this question because they can only imagine living longer while being unhealthy.

blitzar• 4 years ago

Average life expectancy in the US is 78, with some states seeing average age around 74.

Do you want to live no longer than average, so lets call it no older than 75?

chimen2• 4 years ago

Because I'm so "so smart, intelligent and clever" and the alternative is unknown to me. Simple 1+1

boredemployee3• 4 years ago

Exactly!

vorpalhex• 4 years ago

If I could have a thousand years to read and study deeply and just write and think, I would take it.

Yes my loved ones will die and that will make me sad. I'll grieve and move on. My life is not theirs - their death does not mean an end to what I am doing.

Flip the problem. If you could bestow a friend/family member with a thousand years, even knowing you will die, would you?

One of the ancient greek prophets declared the apocalypse would happen in 9 generations. She was quite wrong. Most doomsday prophets are (well, probably all but the last one).

ltbarcly32• 4 years ago

The people you love can take it too?

w10-13• 4 years ago

"a reason to stay alive while people I love are dying"

I'd like to be healthy enough to help them when they are dying.

CalRobert2• 4 years ago

the gist of it

""" The scientists have tested different time windows of short-term drug administration in fruit flies and found that a brief window of 2 weeks of rapamycin treatment in young, adult flies protected them against age-related pathology in the intestine and extended their lives. A corresponding short time window, 3 months of treatment starting at 3 months of age in young, adult mice, had similar beneficial effects on the health of the intestine when they were middle-aged.

“These brief drug treatments in early adulthood produced just as strong protection as continuous treatment started at the same time. We also found that the rapamycin treatment had the strongest and best effects when given in early life as compared to middle age. When the flies were treated with rapamycin in late life, on the other hand, it had no effects at all. So, the rapamycin memory is activated primarily in early adulthood”, explains Dr. Thomas Leech, co-author of the paper. """

And here I am wondering what the cutoff is for middle age...

dsign2• 4 years ago

When somebody asks about what is the next big thing, I always think on anti-aging. If you think that you don’t want to live forever, imagine that today when you arrive home you find a note saying that you will die exactly 1531[^1] days from today. How would you feel?

With that said, I would stay away from miracle drugs, because no two human beings have the same physiology. But that’s not an unsolvable problem.

[^1]: It’s a random number to “erase hope”. Not knowing when we are going to die keep us slightly hopeful and perky, our mind away from the problem.

abcc8• 4 years ago

I would argue that a miracle anti aging drug would work well for the majority of the population, much like NSAIDs work well for the majority of the population. Bonus points for being cheap and easy to synthesize.

lijogdfljk• 4 years ago

Honestly, at peace lol. I don't really care about living.

My primary desire for living atm is keeping my family safe, providing for them, etc. Beyond that, i am living just because i am - and i enjoy life as much as i don't want to _not_ enjoy time i'm here anyway.

rr888• 4 years ago

I agree. But would be interested in staying younger/stronger/healthier for the same lifespan.

fatuna• 4 years ago

I think this is a great example of "what's good for the individual, is bad for humanity as a whole". Imagine we'd discovered a drug that adds 100 years to a persons natural life. Now imagine this drug was discovered 100 years ago. J.D. Rockefeller and the likes would still be alive and influencing politics. I can't even begin to think how much humanity would stagnate after such an invention.

See also the Planck principle: "A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it"

https://en.wikipedia.org/wiki/Planck%27s_principle

dsign2• 4 years ago

People don't need life-extending drugs to hold onto power or ways of doing things, that's what dynasties are for. And if in a democracy somebody like J.D. Rockefeller gets a voice that is too loud, then the democracy is flawed and we the citizens are ultimately at fault.

criddell• 4 years ago

If you sign your dog up for the Dog Aging Project[1], you can get rapamycin for your dog.

[1] https://dogagingproject.org/

ilaksh• 4 years ago

The idea that you could just take a pill one time and be "protected from aging" or something sounds ludicrous. Would be interested to see people reproduce these results and have them supposedly transfer over to humans. Humans are a much longer time scale.

I always go back to the SENS concept of having several different problems to solve related to built up damage, cells that won't die, etc.

sdenton4• 4 years ago

It's definitely not a one-time thing... There's a fascinating Radiolab episode on the the history of Rapomycin, including discussions of the mechanism of action: https://radiolab.org/episodes/dirty-drug-and-ice-cream-tub

The basic hypothesis is that cells operate in two modes, one storing up stuff in times of plenty, and a second mode which uses up the stores and cleans up, active during lean times. mTor is supposed to be the chemical signal which indicates which mode to act in; it's inhibited by both fasting and rapomycin.

Teever• 4 years ago

People used to feel the same way about vaccines.

Now we have vaccines that eliminate a specific form of cancer.

Perhaps we will find a way to pack all the different treatments for the various SENS forms of aging into a single one-time pill.

Maybe it will just be self-replicating nanobots.

What a fascinating time we live in where we can actually start to make educated guesses about the viability and timeframe for these kinds of things.

hericium2• 4 years ago

This isn't new. David Sinclair wrote about rapamycin in Lifespan[1][2] (I keep linking this book on HN a lot; no relation)

[1] https://en.wikipedia.org/wiki/Lifespan_(book)

[2] https://lifespanbook.com/

shuntress• 4 years ago

Anything David Sinclair has endorsed should be considered with at least double the normal skeptical scrutiny.

dennis_jeeves1• 4 years ago

Lol, why do say that? I had the same impression of him.

It appears that people fall for his niceness is my theory about him. And no doubt he is a nice guy. It's just that his explanations lacked the rigor I generally look for.

hericium2• 4 years ago

I don't think he _endorsed_ rapamycin or metformin. If he endorsed anything, I'd say it was NMN.

Everything people like Sinclair state should be taken with a grain of salt (as even his peers say he's guilty of making excessive claims) but it's forward-thinkers who change the world, not people following others' steps and afraid to take peek outside their box.

Maybe the guy will achieve something real in the field and maybe it'll be the next guy. No way to know. But I'm far from dismissing someone just because their opinions are not in line with popular knowledge. Boltzmann, Galileo, Copernicus and Wright brothers were discredited or ridiculed.

nradov• 4 years ago

Dr. Peter Attia did a thorough summary several months ago of what we know about rapamycin as an anti-aging therapy. There are plausible reasons to think it might be safe and effective, but human studies are lacking. This is a promising area for future research.

https://peterattiamd.com/ama35/

derbOac• 4 years ago

Maybe I missed this, but 2 weeks in fruit flies and 3 months in mice probably translates into something much longer in humans, on the order of a year or two maybe, if not longer? That's a pretty long time to be on an immune-suppressing drug with pretty significant side effects.

It's still an important bit of information if it replicates, but I think it might not be as clinically practical as it sounds from the press release.

pstuart2• 4 years ago

Not just the quantity of extended time, but the quality of that time matters too. Even if life wasn't extended a day but one had greater vigor/vitality/cognition it would still likely be a worthy pursuit.

adamgordonbell2• 4 years ago

Anyone taking or have taken Rapamycin or things that change mTor? How did that go? Is there risk of infections?

David Sinclair got me interested in this topic.

Also people who fast for a long time: How do you do that? I get super hangry and find it really a struggle past a certain point of not eating.

colechristensen• 4 years ago

The super unpleasant part of fasting is a phase that ends.

kubami• 4 years ago

I fast a lot, right now I do 36 - 72h every 6 - 8 weeks.

The hardest moment is right when your body is about to switch from using glucose to using ketone bodies for energy. After that the hunger, feeling anxious, etc stops.

The time it takes to get to that point (when feeling "bad" intensifies) and how long the transition takes can be influenced.

Primarily, by what you eat before you fast. In general, avoid eating carbohydrates, especially simple carbohydrates like sugar, fruits, past, bread, etc. I usually eat more protein and fat before fasting.

Another "trick" during fasting is to cheat your stomach a bit by filling it with liquids - I drink lots of water and tea.

The main thing to remember - it will pass, and you will feel great after your body switches. Your mind will tell you that it will just progressively get worse the deeper you get into the fast - it's not true :)

yazaddaruvala2• 4 years ago

Oh I forgot about the tricks. Thanks.

I also use the tricks mentioned above. They are very useful.

Additional tricks:

- Use fiber supplements in your water sometime in the middle of your fast (simplest time is in the morning in lieu of breakfast). I use psyllium husk.

- Soup (or rather broth) is a fasting bff. Remember miso, herbs, spices, salt, do not have calories. Flavor your water liberally. Change up the consistency with stuff in it (green onions, seaweed). Change up the temperature (hot, cold, whatever). I even add psyllium husk to my soups to change up the texture and consistency just for the variety. Remember you can “eat” a lot of tasty stuff while still technically fasting.

- Actively (rather than passively) deplete your glycogen stores. Do a workout ideally including cardio, then do your best to immediately fall asleep to recover. I can sleep through anything, if you can too you’ll be in keto by the morning and no real feelings of difficulty.

- Remember to take a multi-vitamin daily while fasting. Make sure it doesn’t have sugar like those “vitamin C hangover powders” or “electrolyte water stuff like Gatorade”.

yamtaddle2• 4 years ago

I've dabbled in fasting and found my ability to do it comfortably varies a ton day-to-day. Some days I'm craving food by noon and/or am very tired and practically can't think at all by 3PM (this is pretty bad on work days, obviously, but not really great on any day). Other days I can go from wake-up to lie-down without a single bite of food, and hardly notice a thing. I can't tell in advance which it's going to be, so rather than sticking hard to a fasting schedule, when I'm in the mood to do it I'll pick days to try, and if at some point it becomes clear I'm gonna wreck my whole day if I persist, I bail and eat a meal. Ends up being about 50/50, days that work out and days that don't, if I try a couple days per week.

Sometimes I can approach 48 hours before I start to feel bad, other times I can't even make it one day before I'm a mess and can hardly function. I'm sure the difference has to do with blood sugar timing and/or what I ate the day before or something.

yazaddaruvala2• 4 years ago

Human bodies are crazy cool.

1. There is some internal clock that we don’t yet understand but clearly exists. Specifically your digestive track proactively activates itself in preparation for food. Then if food doesn’t come, your stomach will “growl”. It takes a 1-3 months for your clock to readjust such that it doesn’t do that. After this you will not “feel hungry”. If you intermittently fast for a year or so, you will likely never again “feel hungry”.

2. Eating meals is a habit. Arguably more addictive than smoking. But like with any habit, it can be broken. This isn’t the feeling of hunger… rather a weird compulsion. If you stop fasting for a few months, this will need to be rebroken every time. I’m currently struggling to re-break it.

3. The social pressure to eat is real! This is the hardest to contend with.

Good luck :)

mordechai9000• 4 years ago

On point #3: there seems to be something about being on any kind of restricted diet that makes people want to feed you.

fayalargeau• 4 years ago

that was my favorite podcast, but he did say that he stays away from it because it's meant for people who need it as an immunosuppresant

runnerup2• 4 years ago

Also people who fast for a long time: How do you do that? I get super hangry and find it really a struggle past a certain point of not eating.

Different people have different responses to fasting.

It's always been very easy for me to fast by becoming "at peace" with the feeling of hunger for the first 2-3 days, and after that I don't even notice. But later in life something about my body changed and my response to fasting was much more severe and I was suddenly unable to fast for more than 1-2 days due to extremely strong urges to eat, irritability, etc. This happened for 2-3 attempted fasts around the age of 32. A year or two later, and fasting is suddenly "easy" for me again. To be clear, the first 2-3 days usually sucks regardless.

I suspect that I am generally very good at metabolizing fat. When I get blood tests while fasting, even if I haven't eaten anything at all in 7 days, my glucose is generally still well above the minimum of normal, even sometimes towards the high side. I suspect that if my blood sugar was low, I'd have much more difficulty. It does seem to take 2-3 days for my body to "switch" to metabolizing fat at a high enough rate to raise my blood sugar up.

I also suspect different people have very different reactions to low blood sugar.

Just as a note, for me one of the biggest determinants of a successful fast is control over my environment. If there are people in my home cooking great food every night at the same time, it's very hard. If I'm living alone and let my fridge get empty, it's much easier. I've also dealt with it by shifting my work hours to leave later and come home after my partner has finished dinner and cleaned up the kitchen. But this is orthogonal to the above issue.

ve553• 4 years ago

I have been taking rapamycin for many years now. It's obviously not ready for anywhere near the general public and is never something I'd suggest to someone at this point, but my own results have been wonderful and my blood panels and energy levels are great. If I had to guess, when properly used, this would probably add a full 5-10 years onto the lifespan of a lot of people. When combined with many other promising treatments, I think we could easily add 10-15 years onto most peoples' health+lifespans.

jesuscript3• 4 years ago

How do you get it?

ve553• 4 years ago

most people either find a rare doctor that will prescribe it to you or purchase it without a subscription online

bigmattystyles• 4 years ago

Hopefully they mean aging remedy not anti-aging remedy...

evo_93• 4 years ago

I'm a month into taking rapa and already I feel like it's having a noticeable effect. I'm curious what others on this threads dosage looks like. If you prefer to keep it private, you can email me directly (my email is on my profile).

I'm currently taking 2mg once a week on my rest day; I started with 1mg and after 1 month added another MG. I'll continue each month until I reach 8MG once a week, which is the dosage the doc I worked with in Texas to get my prescription recommended and most people seem to take.

Also - I would say that NMN + Rapa is a completely life altering combination for anyone 50+. I feel like I can lift harder and longer now than when I was in my 40's and things seem to be getting easier the farther into my rapa routine I get.

Also also - you can find rapamycin online / overseas under its other name - Sirolimus - and the cost is a little lower than getting a proper US prescription.

pstuart2• 4 years ago

Finding a doctor who's up to "non-traditional" support can be a challenge, but you've inspired me to start that search.

Traubenfuchs3• 4 years ago

Besides satisfying their altruism they have nothing to gain and everything to lose if this miracle drug causes cancer in 5 years.

I read up ok it. It can literally cause cancer.

evo_93• 4 years ago

This doctor will prescribe it, he does telemed / remote calls, works out of Texas: https://www.theprivatepractices.com/services/rapamycin

gadders2• 4 years ago

What's NMN?

runnerup2• 4 years ago

Nicotinamide Mononucleotide, an unregulated supplement.

Note also:

We found that, when data from all organisms studied were combined for each compound, aspirin resulted in the highest percent increase in average lifespan (52.01%), followed by minocycline (27.30%), N-acetyl cysteine (17.93%), nordihydroguaiaretic acid (17.65%) and rapamycin (15.66%), in average.[0]

Though I'd consider whether flies and worms are good models for your human self.

0: https://pubmed.ncbi.nlm.nih.gov/34687363/

evo_93• 4 years ago

Yeah as others appointed out it’s a nad+ precursor.

I feel compelled to comment though because anytime I read about how this stuff is only been tested in worms in mice… That automatically discount it’s worth as something to consider.

I’m gonna sah what I said before - I’ve played high-level hockey my whole life, I’m now 55 and I play against guys that barely washed out of their pro career.

When I stop taking nmn for two months my speed dropped from 20+ Mph to the mid teens.

A week after resuming my NMN supplementation my speeds are back in the 23-24 mph range

There’s just no way to fake it against players of this caliber. And to be clear I don’t know anybody even close to my age competing at this level.

jamesdmiller• 4 years ago

I have been taking Rapamycin for 19 weeks and NR and Metformin (for anti-aging) for much longer and I can't see any difference. I'm 50+. I generally, however, feel excellent, as well as I remember when I was younger so long as I have gotten lots of sleep and don't have a cold. When I'm sick or tired I feel much worse than I did, however.

rdedev• 4 years ago

After reading the following article I've tempered my expectations from ramapycin

https://khn.org/news/a-fountain-of-youth-pill-sure-if-youre-...

The drug has been known for a long time but human trials always seems elusive

phkahler• 4 years ago

> The drug has been known for a long time but human trials always seems elusive

Human trials of this will likely never happen. At least not publicly.

ltbarcly32• 4 years ago

Why is that? Literally nobody will do the research in any country in the world because the Illuminati are everywhere?

bookofjoe• 4 years ago

https://news.ycombinator.com/item?id=32653737

yasp2• 4 years ago

FYI one study shows that rapamycin increases amyloid-beta protein plaques in the brains of mice.

https://neurosciencenews.com/rapamycin-amyloid-beta-20770/

shiftpgdn• 4 years ago

All of the original data around amloyd-beta protein data was faked. A lot of it was even just outright photoshopped. https://www.science.org/content/blog-post/faked-beta-amyloid...

yasp2• 4 years ago

FFS. I forgot about that.

tptacek• 4 years ago

That seems like an extremely oversimplified summary of the article you've linked to.

resoluteteeth• 4 years ago

Amyloid beta may not cause alzheimer's disease, but you still don't want amyloid beta plaques in your brain. They may not themselves be causing damage but they are almost definitely a sign of damage to the brain, so anything that appears to increase them should be handled with extreme caution.

Traubenfuchs3• 4 years ago

Side effects can be pretty serious, bordering into "probably deadly for a few people" territory.

https://en.m.wikipedia.org/wiki/Sirolimus

globular-toast• 4 years ago

There seems to be a growing trend of generally healthy people looking for drugs/supplements to provide marginal improvements. I can't help thinking it's a sign of a vacuous and unfulfilling life. Instead of spending time and money on drugs to increase your life span, why not spend that time/money on actually living your life? I think this probably comes down to the general boredom that comes from not having a family and not having enough time off work to do anything else worthwhile.

gruturo• 4 years ago

There seems to be a growing trend of generally healthy people looking for drugs/supplements to provide marginal improvements. I can't help thinking it's a sign of a vacuous and unfulfilling life.

Not sure I agree with your analysis. If I had a vacuous and unfulfilling life, I wouldn't strive to prolong it.

jonathan-adly3• 4 years ago

Just putting this out there, I am a PharmD and this is totally real and the traditional medical establishment is really behind. It is positive effects are beyond doubt - the argument against it is usually "we don't know what the side effects if 100m+ went on it for 20+ years". (which is also 100% true, but that's where patient autonomy comes in). Also, there are some questions about how much are really the positive effects.

Anyway, I am tinkering with something in that space - feel free to reach out if you want explore being a co-founder. (email in about)

Traubenfuchs3• 4 years ago

Do you have a personal comment on the long and scary list of side effects it causes?

actually_a_dog• 4 years ago

One of the big confounders there is that it typically is given to people undergoing chemotherapy, not otherwise generally healthy people.

jonathan-adly3• 4 years ago

As someone already said - rapamycin literature is mostly in cancer and transplant patients and with relatively high-doses. The risks are real, but my clinical judgement would lead me to believe that for at least some people the benefits would far outweigh the risks

BiteCode_dev• 4 years ago

What makes me scared about this is that it's immunosuppressive. The immune system is a very important part of the human body, and I worry that taking it could have terrible health impact after years of acting on your body lines of defense.

What can you tell me about it?

jonathan-adly3• 4 years ago

Your concern is correct. Suppressing the immune system is a 2-edged sword - a little suppression in the right setting, is extremely beneficial, but go overboard and it is harmful. That's why in a perfect world, we would have large human trials with different dosages and iterate until we can get the maximum benefit and the least harm.

The problem is, no one wants to do those trials because rapamycin is cheap and generic. Why would Pharma spend money on something that they can't patent? Also, these kind of trials have to go on for 10+ years at a minimum - which is cost-prohibitive even if it is patentable (not to go in the weeds, but long trials count in the period of exclusivity given to pharma patents).

I believe the right approach is to use it off-label, be upfront about the potential risks, and collect lots of data so you can improve as you go. Practical anti-aging so to speak.

Another approach is through the NIH grant pathway, but that has a lot of road-blocks as well.

andy_ppp• 4 years ago

Is the dose for immune suppression the same effective dose for longevity, i.e. how many mg/kg body weight are we looking at for each thing?

It seems pretty safe anyway from my understanding…

adrian_b• 4 years ago

According to the abstract of the article, its effects, at least in that form of using it, were not immunosuppresive.

On the contrary, the protection of the intestine to aging effects was due to increased autophagy in the intestinal cells, which eliminated the defective cells, and by increased levels of antimicrobial lysozyme, and these effects persisted long after the initial treatment ended.

tepitoperrito• 4 years ago

There's a study on pubmed that suggests it is more immunomodulatory in action than suppressive. I'll update this if I find the link.

Edit: it's an opinion article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/

derefr3• 4 years ago

If you think about it, there are specific parts of our immune systems that are likely entirely maladaptive given modern civilization, where people are ~never exposed to parasites, animal venoms, etc.

We can turn those parts off, while leaving everything else on, and be better for it (no allergies, psoriatic arthritis, MS, Chron’s, etc.; and so none of the accelerated cellular senescence those conditions provoke in affected tissue.)

A lot of recent pharma is already focused on doing specific forms of this at low levels. Every other drug ad in the US is for an immune-receptor blocker of some kind. And the side effects of these drugs come down mostly to the fact that they’re too low-level — they stop these parts of the immune system from being called into action at affected sites, but they leave it active and “patrolling”, such that it attacks harder any tissues that don’t absorb the receptor-blocker well, and such that you get withdrawal effects of potential inflammatory crisis if/when it wears off.

Just deactivating the relevant parts of the immune system entirely, on the other hand, provides the same benefits these drugs do, but with none of the “now the rowdy enforcers have nothing better to do, so they go looking for trouble” drawbacks.

crypticlizard• 4 years ago

Could you comment on if you think there is a natural analogue out there? Even if less effective? For example a quick google search led me to this: https://www.nutraingredients-usa.com/Article/2017/12/01/Ashw...

Which is suggesting Ashwagandha might a candidate for Rapamycin and Metformin mimcry.

fnordpiglet2• 4 years ago

If you eat dirt from Easter island you’ll get some and it’s totally natural.

woshea901• 4 years ago

Some good discussions on rapamycin and longevity on Reddit at https://www.reddit.com/r/Rapamycin/

born-jre• 4 years ago

hmm science.

I wonder what happens if someone overdosed in anti-ageing drug, do they turn into baby.

firecraker• 4 years ago

fnordpiglet2• 4 years ago

I just have this painting of myself that keeps getting older

deegles3• 4 years ago

I'm 35, have been taking 6mg of rapamycin per week for about a year. It's hard to assign the effects directly to it since I've been taking other supplements and also fixing up my diet + exercise. That being said, I am quite sure that it has reduced general aches and pains, reduced visceral fat and I now have less gray hair compared to when I started. It did slightly increase my glucose and lipids, but still within safe ranges AFAICT. I'll continue to take it until I notice real adverse effects.

WastingMyTime892• 4 years ago

This comment is quintessential to the issue with HN.

So you are quite young, just had a complete change of lifestyle and your take away is that the beneficial effect comes from the drug you take randomly amongst a cocktail of other things.

Interesting.

deegles3• 4 years ago

It was not a "complete change" in lifestyle. Please don't make assumptions beyond what is written.

DoreenMichele2• 4 years ago

I now have less gray hair compared to when I started.

I've never taken rapamycin nor even heard of it before today. I have less gray hair than I had twenty years ago.

My understanding is that gray hair suggests a B vitamin deficiency, especially PABA, and a need for adrenal support.

lps41• 4 years ago

I have less gray hair today than 5 years ago - I think that’s pretty easy for aging men to achieve. ;)

coolstepa• 4 years ago

There is a super interesting Radiolab episode on the scientist who discovered Rapamycin, and how he himself was taking it to combat colon cancer. It's really good, and the ending has you quite puzzled.

https://radiolab.org/episodes/dirty-drug-and-ice-cream-tub

tootie• 4 years ago

Yeah, the story is absolutely bananas. Not just the personal effort of the scientist, but what in the world even made them think to try any of this. The "Rapa" in the name is from Rapa Nui because this was a chemical found in a random soil sample from Easter Island. This deserves some conspiracy theories.

enviclash• 4 years ago

If it is a reliable alternative to a medicine with similar effects, I advocate for fasting. I try doing it once per week until 2pm, and once per month till dinner. At some point (years in my case) it became a pleasure.

w10-13• 4 years ago

Please, people. It's bonkers to jump from fruit fly results to humans.

Before you take any drug chronically - particularly something KNOWN to block a gene cascade receptor - be sure there are good studies (sufficiently powered, peer-reviewed, phase-III studies in humans with actual endpoints and significant positive results).

And be sure the "researchers" you're relying are not just PhD's or retired doctors regurgitating dubious studies.

Remember: the essence of a good scam is that it is partly true.

Readers will get more longevity from walking instead of reading these studies. Avoiding toenail fungus will improve your lives more. Those have real data behind them.

quanum_burrito• 4 years ago

I have taken this drug several times of the past 10 years. Each time it had a different effect on my immune system and body systems. The first attempt, it really helped with ridding my body of sustained fluid in my lungs. In more recent times it had helped with the same thing. I have a lung disease and it's not a simple thing to treat so they take care to treat it with some new treatments like rapamycin. I am simply stating that I had different and somewhat difficult times while being on the drug. The lung disease that I have is not common and I am immunocompromised, so being on an immunosuppressant drug like this really made me feel ill. I had the influenza A one year while being on it, as well as a couple of cases of pneumonia that put me into a funk. I am glad I was on it, though because it got me to where I need to be. The liquid form tastes disgusting( ya gonna need a chaser) but the pill is not so bad. It did really effect my joints and muscle systems, I was taking from 2 mg down to .5 mg and each time the doses made me feel extremely tired. I am glad that this med is helping people and I hope all that are taking it, are taking this medication seriously. It is no easy task to be on. Drink lots of water. Best wishes

mlinksva2• 4 years ago

https://rapamycinstudy.org/ is collecting data on off-label use according to https://www.fightaging.org/archives/2022/04/collecting-data-... (reasonatllm who runs that site hasn't commented on this site recently, perhaps they are busy running https://www.repairbiotechnologies.com/)

mlinksva2• 4 years ago

Whoops, I meant reasonattllm.

nikolay• 4 years ago

There are other natural mTOR inhibitors:

- EGCG (found in green tea)

- Vitamin D3

- Curcumin

- Resveratrol

- Genistein, an isoflavone found in soybeans

- 3,3-Diindolylmethane (DIM), found in cruciferous vegetables

- Caffeine

Fezzik• 4 years ago

Tangentially related - it seems there are other things that, if experienced early enough in life, have significant health benefits that are triggered if-and-only-if the catalyst occurs at the right time. For example, pregnancy at a young age is associated with a significant decrease in breast cancer risk. My recollection is this benefit of pregnancy disappears once a women is in her late teens. Our bodies are wildly interesting.

https://pubmed.ncbi.nlm.nih.gov/24355762/

Rapamycin, drug used in cancer therapy, emerges as powerful anti-aging remedy

Related Stories