A cheap, generic drug became a darling of longevity enthusiasts | Hacker News Reader

A cheap, generic drug became a darling of longevity enthusiasts

washingtonpost.com

47 pointsdtawfik166 comments

I’m surprised this article wasn’t about Metformin, something gwern has written about[0] and has some popularity in the entire nootropic circle of people that I know.

[0] https://gwern.net/longevity#metformin

My god, smart people can be dumb sometimes:

"probably also offers only a constant reduction in risk without decreasing the acceleration of risk, if for no other reason than hundreds of millions of people have taken metformin over the past century yet no gerontologist has ever noticed a massive overrepresentation of diabetics among centenarians"

Ummm, and also WW2 planes that made it back to the base had damage in the least crucial areas.

Sometimes being smart means you're better at rationalizing your beliefs.

That’s a common refrain, and I guess seeks to explain academic blind spots. But I do wonder if it’s not rather a form of victory disease where some of your intelligence can effectively shield you from the consequences of your stupidity allowing to hold incorrect beliefs far longer.

As best I can tell the smartest people hold more true beliefs and have fewer blind spots which has me leaning towards the latter explanation. But as this is purely based on my subjective observations it’s possible that this is merely the result of my own biases.

I wouldn't surprised if that factors in as well.

Metformin has been under scrutiny in recent years, several big studies failed to reproduce, and I'm pretty sure the consensus right now is that it's ineffective. NAD precursors are going through the same thing right now as far as I know.

https://archive.is/qWfiA

Radiolab did a story on it. It's really bizarre how it was discovered and popularized

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

rapa-nui-cin

I wouldn't say Rapa is cheap. Even if you can source the cheapest indian brand (which is challenging if you don't know how to navigate that market), it will cost you $10/week. And it's something that you do consistently, over years and decades.

Jack LaLanne, exercise guru and healthy-eating aficionado lived to 96. His brother Norman, who did none of the things his brother did to the same level, lived to either 96 or 97.

This is no different than "my grandmother smoked a pack every day and lived to 130."

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On a related note, I love posting this study https://jamanetwork.com/journals/jamanetworkopen/fullarticle...

Look at Figure 2C in particular. The hazard ratio of smoking is 1.41. The hazard ratio between "Low" (<25th percentile) and "Below Average" (25th-49th percentile) cardiovascular health is 1.95.

In other words, it is better to be a smoker than in the lower 25% of non-exercisers. By far. It's not even close.

Clickbait avoidance: it's rapamycin.

i thought it was going to be metformin

"Longevity enthusiasts" sound like people who spend like 1/10 of their time on Earth desperately searching for ways to live several weeks longer.

Haha it's true but that's why it's a good thing they exist. They burn all that effort. We reap the rewards.

Eight year Olds posting?

14% longer in mice trails is more than a few weeks. Regardless of if it’s “desperate” or not, there’s worse ways to spend your time than searching for a way to live another decade.

14% of a mouse life is several weeks.

Most obtuse poster award goes to…

I laughed. :)

Would seem more obtuse to me to assume that a gain of 14% for mice in a lab-situation would translate to a similar gain for humans in a real-life situation.

No one is assuming that. People are assuming it's _worth looking into_.

Where to next, Algernon?

For human males castration results in a very significant increase (10+ years).

Yeah but testosterone makes life worth living.

Yet castrated men don't commit enough suicide to lower their life expectancy.

Is that caused by testosterone’s direct physiological effect on the body or something like increased risk taking?

If they spent that extra time taking more care what and how much they eat and add some exercise, the effects would be much more pronounced (and they would be probably much happier too). But yeah sometimes even very smart folks end up in some analysis paralysis and tunnel vision.

Oh god, I've already had to hear Peter Attia talk about this for years and now newsspam sites are catching on?

Spoiler: pound it all you want, everyone still dying of chronic illness, diabetes, cancer, heart failure, etc. Eat clean and exercise it's your only chance.

I think Attia’s spiel is that you eat clean, exercise, and take rapamycen. It’s not like those are exclusive options.

In his book he also goes into how it would be silly to skip the important pieces like diet and exercise and only get to the med portions.

Indeed, and in fact he called the risk profile of rapamycin as picking up a dime in front of a tricycle. It's low risk but low reward.

He's also said if you can't deadhang for 2 minutes or farmers walk 2x your body weight, no longevity drugs are likely yo make more of a difference then getting stronger.

I recall him saying he wouldn't recommend people younger than about 40 take mTOR inhibitors too, worth noting for young longevity enthusiasts. As I understand mTOR activation/inhibition is a tradeoff between promoting and inhibiting "growth" and the latter is counterproductive for young people. IIRC high meat/protein diets also activate mTOR, which might partially explain why primarily plant-based diets are associated with longer lifespans. Fasting also suppresses mTOR, so mTOR inhibitors are sometimes promoted as an easier way to achieve (some of) the same benefits more easily. On the other hand fasting elevates cortisol which inhibits testosterone. I don't know if mTOR inhibitors like rapamycin have the same effect, but it's also a health concern.

Suppressing testosterone has important benefits for longevity. It reverses the atrophy of the thymus gland, therefore it makes the immune system more effective.

That's a high target. Farmer's walk 320 lb on 160 lb? Holy shit that's heavy.

Longevity drugs don't make a difference till that point? Might as well be useless since I think very few people can 2x BW deadlift. If you lift you can do it but most people don't lift heavy.

I may have the numbers wrong. Maybe it was body weight? He had v02 max goals as well. The point was the you lose muscle and cardio fitness as you age, and that leads to decreased health span. You need headroom in those as you age and that will help more than anything else.

In “Outlive” Attia said the goal was for men to farmer’s carry their body weight for a minute (half BW per hand).

Yeah, I’m not sure exactly what he is basing that one. A 1.5x farmers walk for 10-20m is exceptionally strong in my book.

A normal 6' tall 200lb man should be able to farmers walk 400lbs?

I don't think so.

> farmers walk 2x your body weight

no way (no weigh) that's right. deadlifting 2x body weight is pretty significant and i've spent a ton of time around pro athletes.

I basically agree with your general sentiment but I think if society is going to really, actually fight mortality, something drastically different has to happen.

I don't think rapamycin is that thing but at some point in the future something — or more likely, some things — outside of healthy living are going to find their way into our medical arsenal.

Yamanaka factor-based genetic and chemical treatments that remind your cells’ age. Already showing results on organs like eyes. They’ll come to the US slower than they come to medical tourism destinations.

We are nowhere near being able to guarantee safety against teratoma formation after epigenetic reprogramming. If this type of intervention ever becomes practical, it will be in the distant future.

in other words, we refresh your genes but now that they're new and fresh again they may get cancerous?

I take it that you're not a fan of his book - could you outline why, or whether there are any better ones? Thanks.

The whole longevity movement is also mostly driven by fear of death. OK, so you take every drug under the sun in the hope of living another day. In order to what? Be a wage slave for longer? Spend more time on Medicare?

Yeah why don’t we blow up the planet today instead of another day of wage slavery or Medicare?

The idea is to keep living and stay healthier longer, because living is good and the future is bright.

That's quite a jump, and it's very telling.

The planet would actually be much better off without humans living on it. Why blow it up? Leave it to squirrels and manatees and so on.

The planet doesn't care one way or the other

That's a depressing viewpoint, since that's true, even if you don't manage to find the fountain of youth. Life has joy and meaning. If you have a purpose, whatever it is, then every singlenday longer you're alive is another day you get to help people, to educate them, to heal them, to ease their suffering, do good for the world, spend time with friends and family; whatever!

It’s interesting how my one and only motivator for these things would be the things you mention. I could imagine discovering a zest for life where I decide to take on such longevity advice. On the other hand in the modern age there are now thousands of subcultures for all kinds of things where the people who practice them must surely treat it at least like a hobby (meaning a serious pursuit). So I wonder: are they doing it as a means to an end because life-is-great? Or has it taken on its own life and it’s now being done for the sake of it?

There’s just an overwhelming amount of information and advice out there from all these subcultures.[1] What would I do if I found a burning meaning in life? Maybe adopt an eclectic set of advice and lifestyles from all these subcultures as a means to the end of living longer and better?

[1] And I know: eat well, exercise... the basics are not complicated. Intellectually speaking.

You say that like it's a bad thing. Vast majority of people don't want to die or grow sick and enfeebled with age. It's like observing that the reason people usually don't leap off tall buildings is because they fear falling and death - true, but obvious.

If people prefer being alive and healthy, and they obviously and overwhelmingly do, then we should be looking for solutions. If people want to escape the drudgery of work they are free not to take whatever medications or treatments are discovered - but the tiny minority that prefer death to labor shouldn't restrict the rest of us.

This is very selfish. As the population gets older we'll have fewer and fewer workers supporting all the healthy and long-lived old farts. The young will be taxed to within an inch of their life, causing their lives to be more miserable than they already are.

Before you get that dopamine hit from hitting that downvote button, ask yourself this: can more or fewer young people afford to own a home now? Why? Are they really that much more "lazy" than their parents generation?

Not at all. The only reason we support the elderly now is because they're unable to work. In a world of negligible senescence the old will support themselves.

So overpopulation via geriatrics is good but overpopulation via birth rate is bad? What's the benefit of running the planet-wide distributed human computer with ancient parts held together by drugs rather than new replacement units?

The benefit is that you and your loved ones don't sicken and die with age.

You are talking about individual benefits. I am talking about the entire humanity. Cancerous cells also benefit from having their kill switches deactivated. They just happen to kill the system that they are a part of while optimizing for their own survival. I am making the point that selfishly wishing to live forever is exactly like that.

You aren't making that point so much as asserting it without evidence. There is no reason to think longer lived humans will contribute to extinction. Perhaps thousand year old scientists and economists will figure out solutions to humanity-threatening issues that would have gone undiscovered and longevity will, therefore, save rather than doom humanity.

Just because you can imagine that, but not really articulate how, longevity might be bad for humanity doesn't mean you've made an argument.

> can more or fewer young people afford to own a home now?

More. Gen Z is ahead of previous generations. “30% of 25-year olds owned their home in 2022, higher than the 27% rate for Gen Xers when they were the same age.”

> Why?

Low interest rates during the pandemic helped, but generally homeownership stays steady regardless.

> Are they really that much more "lazy" than their parents generation?

Huh? Oh, did you assume the answer was “less”? Guess you should have looked up the numbers first, or at least not gotten your ideas about the world from Reddit.

It is interesting, isn't it? Statistics show that everything is rosy, and yet people's lived experience doesn't seem to match: https://www.politico.com/news/2024/03/05/biden-headaches-sta...

You dismiss Reddit so readily. You must believe 90% of Russians support Putin. After all, that is also an official number published by a government authority.

Living is nice. I like living. Living longer means I spend more time with my children and more time with my grandchildren. This is nice too.

What's this shit-posting driven by, fear of hearing your own thoughts?

Well, you took time out of your day to respond to it, so let me ask the same question: what drove that decision?

I wanted to provide a counterpoint. A lot of people will do anything to hang on to life by their fingernails or teeth. But is it worth it?

> In order to what?

Survive until humans start colonizing space.

Peter Attia doesn't recommend rapamycin for most patients.

https://peterattiamd.com/davidsabatini-mattkaeberlein/

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