On Longevity | Hacker News Reader

On Longevity

eriktorenberg.substack.com

44 pointskevin_hu19 comments

Perhaps the most promising anti-aging drug is metformin.

Type 2 diabetics on metformin live 15% longer than non-diabetics. This is remarkable, considering how big a health disadvantage diabetes itself is.

Metformin seems to mimic fasting somehow, by interfering with mitochondrial function.

For more information, I refer you to David Sinclair's numerous discussions on this topic. He takes 1 gram of metformin per day, with his evening meal.

This is not medical advice.

Recently I’d seen this on Metformin: https://www.science.org/content/article/rare-genital-defects...

It's not.. I could have shown you the most potent geroprotectors but tragically the website is down... https://geroprotectors.org/

You should look into SkQ1 + NAC instead.

> by interfering with mitochondrial function

Which mitigates the damage caused by the toxic components in his evening meal. If the meal is unalterable that's a good move. But most people can do a lot more good by removing the ingredients from the meal that stress the mitochondria, particularly the excess carbohydrates and polyunsaturated fats. That same deadly duo is also responsible for atherosclerosis.

Your assertion depends on his evening meal being deleterious.

https://naturallystrong.me/david-sinclair/

He's got an excellent diet. He's also got very solid reasoning behind metformin supplementation, having done years of research and investigation. He's a smart and respectable guy, operating in good faith with his research, so if you find yourself disagreeing with him over something trivial, it's unlikely you're right and he's wrong.

Implying that metformin is useful only to mitigate hypothetical harms from nutrition (a trivial dispute) is probably wrong.

Across various interviews, he's recommended metformin for exactly the mitochondrial effects you're talking about. He doesn't supplement on workout days to prevent disruption of the healing and recovery. Metformin isn't something that anyone should start taking blindly or blithely, as it can amplify damage from other circumstances, but it's got a clear place in Sinclair's regimen for very good reasons.

Metformin's longevity effects work on a lot of species. It's got solid science recommending it for life extension, like the other things Sinclair uses, but unless you're a doctor, or work with one to create a comprehensive life extension, health, nutrition, and fitness plan, metformin probably isn't a great idea. Sinclair is doing something similar to juggling chainsaws - it's really cool that he can do that, but it's dangerous for amateurs. Too many unknowable factors can blow up in your face.

Then again, maybe it'll be part of a standard regimen in the next decade, and the immortals are living among us.

Whenever the pro death guys show up, and they always do: Summary of pro death arguments:

  Fairness
      Only rich people will get it. (No tech has ever done this.)
      Better to give money to the poor than science. (family, city, state, nation, has proven local investment beats foreign.)
  Bad for society
      Dead people make more room for new, other people. (consider going first.)
      Run out of resources (live people discover/extract/renew better than dead or nonexistent)
      Overpopulation (colonize the seas, solar system, or have a war.)
            Stop having kids
            Worse wars (nukes are more dangerous than having your first 220 year old person in 2136)
      Dictators never die (they die all the time and rarely of age)
      Old people are expensive (50% of your lifetime medical cost occur in your final year. Delay is profitable.) 
      Old people suck.  (death is an inferior cure to robustness.)
  Bad for individual
      You'll get bored. (your memory isn't that good, or your boredom isn't age related)
      You'll have to watch your loved ones die. (so you prefer they watch you?)
      You'll live forever in a terrible state. (longevity requires robustness.)
      Against gods will (not if he disallows suicide, then it is required.)
      People will force you to live forever (they aren't able to do this now, why would they begin to be?)

Do you think less people make progress faster? What's your target level of depriving life of existence? How do you plan to keep mankind robust from extinction events on a single planet? You might just need more people. What do you think our technology would look like if we had 10x less people for the last 100 years? More people make more progress faster. Aren’t you glad your parents didn't decide the world would be prettier or work better without you in it? If great minds like Einstein, Bell, Tesla, Da Vinci etc., were still alive and productive today, the world would be a better place. You're literally asking for others to die out of your fear. The burden should be higher. Have courage. If living longer comes with too many disadvantages, we'll know 100 years from now and decide then.

Man up, save your family, save yourself.

P.S. Curing aging isn't immortality. You die at 600 on average by accident, and if the parade of imaginary horrible things comes true, even earlier.

P.P.S. I personally raised $27M for longevity research (SENS.org).

One argument I saw in a show I recently watched (Ranling of Kings) is that mortality forces us to rely on others to continue our legacy, so we are forced into caring about our community and the people around us. So immortality would lead people to become more closed off. Longetivity is different from immortality of course, but it's still applicable to an extent. Though perhaps it should be up to us to find value in the community, instead of having it forced on us via mortality

Every argument for death strikes me as silly. If anything, functional immortality would incentivize people to be better. Your want relationships to be stable and mutually respectful at a minimum. Marriages would be somewhat hard to maintain - if you were in good health, mid 20s body, and expected to live centuries in that state, lifelong commitments achieve that "quantity is sometimes a quality all its own" effect.

We'll need a different scale of maturity, too - an 18 year old adult in a relationship with a 300 year old adult makes the term "adult" ridiculously ineffective in describing anything meaningful.

Age and death and maturity tie in to almost every aspect of life and culture and human experience. We don't have the cultural tools and concepts that allow for immortality to fit. If it's achieved, the world radically changes and we won't know what those changes will be until it happens. It'd be like tasking Edison with predicting how the internet would change life, or cell phones, or asking Julius Caesar to write about how the germ theory of disease might improve the human condition. We're smart enough to predict small parts of it, but there's a whole world of ideas and behaviors that get unleashed by immortality, and a non-trivial percentage of them are probably counterproductive with regards to humanity at large (immortal Putin, anyone?)

I'm absolutely stumped by this kind of arguments. I have to get back to what Eliezer calls "belief in belief" to process this - you can't possibly actually believe that, you just have a belief that you do. Because since there's nothing in this train of thought about us happening by chance to have the exact optimum lifespan right now, the logical conclusion is that we should work on people having shorter lifespans in order to live better, more community-rich lives, at least up to the point where you get diminishing returns.

Life has its seasons. Children learn, young adults are passionate, older adults are more relaxed but also more set in their ways. A society where the older-adult phase dwarfs the others in terms of duration/population/power probably does make less progress, in the same way that a society overweight on hothead adolescents has more wars.

You're probably young yourself, right? Or for some reason haven't had a chance yet to observe what old age does to cognitive abilities. Old people aren't set in their ways because they lived a long time, but because they literally don't have the capacity to change. It's very much a hardware problem. And it's masked by the fact that dementia is taking the ability for novel thought first and fixed patterns last - so what we're actually seeing around us is people (apparently) functioning perfectly at 60, when in fact they already have years of cognitive decline masked by doing perfectly well on decades of acquired skills and habits.

Actually fixing dementia, even without life extension, would probably be a social revolution easily comparable with gender equality.

The bottom line is that in our short span of time on this world all of our lives take on some sort of shape that in the end is comparable to one another. Many of the choices people make, they make because of this biological limit imposed on us - time.

The result is winners and losers - good and bad lives lived and many fates left by the road starting from the time people are born. Outcomes influenced by where you grew up, by rich or poor, good or bad schools and so on. All one can do if one find oneself at the bottom of the pile so to say is to trade ones time to offset bad beginnings. But life is short.

Time is the greatest equalizer of all, and if i could i would choose to live forever.

This doesn't really need to be debated. It's weird that there are no large-scale anti-aging projects going on in the world. The US has e.g. the BRAIN initiative, and EU runs the HBP (both with little revolutionary output) , but a large scale Longevity initiative has not been created.

This basic thesis about curing aging rather than disease is the core of Dr David Sinclair's book Lifespan.

Though we aren't currently working on aging specifically at https://SoundMind.co, we are focused on improving sleep with one of the long-term benefits being longevity and improved longer quality of life.

We are already seeing the benefits of extending life via exercise and proper diet. Sleep is the next mountain to climb. You can't give people long life if you can't get them sleeping better, and our sleep naturally degrades as we age.

So you will be interested in this study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654999/

Tryptophan -> serotonin -> melatonin -> Mesenchymal Stem cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329089/ https://pubmed.ncbi.nlm.nih.gov/24650016/

The next problem you will probably be looking at is how to use vit K1 to keep calcium out of tissues/organs/glands like the pineal gland and cysteine & manganese to make the most damaging ROS in the body less damaging.

(I'm not qualified in anything!)

Though circadian rhythms are important and is somewhat impacted in the aging population, it doesn't tell the complete story.

This is the research around the first stimulation we are implementing https://academic.oup.com/sleep/article/43/1/zsz197/5613713

There is a criticism of Sinclair's theories in particular on Resveratrol by Stanfield: https://youtu.be/vGmmBJq0NNo https://youtu.be/rpB5hvE96iY

There certainly is, and I expect more criticism, I was referring more to his theory that aging should be treated as the disease.

Kurzgesagt: https://www.youtube.com/watch?v=GoJsr4IwCm4

CGP Grey: https://www.youtube.com/watch?v=C25qzDhGLx8 , https://www.youtube.com/watch?v=cZYNADOHhVY

Reply on news.ycombinator.com