[HN Gopher] Rapamycin: The unlucky history of an anti-aging drug
       ___________________________________________________________________
        
       Rapamycin: The unlucky history of an anti-aging drug
        
       Author : theNewMicrosoft
       Score  : 163 points
       Date   : 2023-05-08 04:59 UTC (18 hours ago)
        
 (HTM) web link (bigthink.com)
 (TXT) w3m dump (bigthink.com)
        
       | robinsord wrote:
       | [dead]
        
       | tysam_and wrote:
       | 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/
       | 
       | A little further (Aubrey de Grey, from SENS originally):
       | 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/turnbu...
        
         | drBonkers wrote:
         | What do you make of all that in the last link?
         | 
         | At a cursory glance, it seems like the biohackers may simply be
         | poisoning themselves on "fission" days and riding the rebound--
         | eventually habituating to the fission supplements (a la arsenic
         | eaters) so they feel less bad on the fission days (which they
         | attribute to mitochondrial repair).
        
           | tysam_and wrote:
           | Thanks for taking a gander! It is a very curious thread
           | indeed (especially as you go deeper and deeper into its
           | depths). Might I ask what makes you feel it is poisoning?
           | 
           | It is safe doses of well-known supplements (and works for
           | other swaps in their classes -- like apigenin, sulfuraphane,
           | etc).
           | 
           | Curious to hear though the thoughts on the poisoning line.
        
             | drBonkers wrote:
             | > Might I ask what makes you feel it is poisoning?
             | 
             | I definitely didn't mean to imply that I _necessarily_
             | believe its poisoning. Apparently the neurotic and anti-
             | interventionist in me reared its head when reading the
             | thread.
             | 
             | I didn't recognize any of the supplement names, and so I
             | didn't realize they all had reasonable safety profiles
             | (individually?).
             | 
             | I think my point still stands though. From what I saw, the
             | outcomes were deemed positive as a function of subjective
             | reports of well-being, without controls. It seems plausible
             | the protocol is having any range of effects (from negative
             | to null to positive)-- I just didn't see anything other
             | than placebo-uncontrolled anecdata.
             | 
             | This is not to discount their efforts! I am truly
             | interested in the subject.
        
               | tysam_and wrote:
               | I think these are very good points! I understand what
               | you're saying better now. :) <3
        
         | api wrote:
         | The reason why anti-aging is hard is that humans are already
         | very long lived for a large high metabolism mammal. As a result
         | it's likely that evolution has already picked most of the low
         | hanging fruit in humans. We're already optimized for decent
         | longevity.
         | 
         | This is why you see so many promising longevity studies in mice
         | that don't replicate in humans. Mice are _not_ particularly
         | long lived compared to humans, so it 's much easier to extend
         | their life spans.
        
         | safety1st wrote:
         | So in the science of fitness, there's a lot of woo, but there
         | are a few really clear wins. One such example in weight lifting
         | is supplementing creatine. It's well researched, fairly
         | inexpensive, the performance improvements are significant and
         | well documented, and it's very safe with side effects being
         | mild and rare. Once you're actually doing the exercise and
         | nutrition part more or less right, it's hard to argue against
         | supplementing creatine. It's used by the vast majority of
         | professional bodybuilders and most experienced weight lifters.
         | 
         | Is there anything similar in the science of anti-aging? Where
         | (A) The body of research is large, well established, and mostly
         | uncontroversial; (B) The benefits and safety profile are good;
         | (C) The majority of people who are serious about this stuff use
         | it/take it/do it.
        
           | [deleted]
        
           | Parmenidea wrote:
           | Do you give any credence to the reports that creatine can
           | cause hair loss? It seems like one study found a link, but
           | nobody has tried to directly replicate it since. Anecdotally,
           | Reddit is filled with stories of people claiming it caused
           | hair loss, though I'm sure there are a ton of confounding
           | variables.
        
           | shagymoe wrote:
           | Anecdotally, creatine makes me angry and a little unhinged.
           | I've found evidence of other people complaining about this
           | but it's not considered a known side effect. YMMV
        
           | xiphias2 wrote:
           | By far the most important thing in anti aging that checks all
           | boxes is excercise and getting nutrition right (no excess
           | fat).
           | 
           | Most of the interesting stuff happens when you focus on just
           | A part: Yamanaka factors are both super powerful, established
           | as reversing the probably most important hallmark of aging
           | and super dangerous (causes cancer) at the same time.
           | 
           | What's promising is the pace of research: in 20 years there's
           | a good chance to have real safe anti-aging available, but we
           | still need to survive until then.
        
             | ubercow13 wrote:
             | What's wrong with excess fat as opposed to excess calories
             | in the form of other macronutrients?
        
             | tysam_and wrote:
             | I really appreciate this comment a lot. Feels like it hits
             | the nail on the head.
             | 
             | I've seen some of the discussion about/around the Yamanaka
             | factors and it feels like an anime plot point, honestly. I
             | need to look more into them and understand them a bit
             | better. They're the ones implicated in stem cells returning
             | back to pluripotency, right (and then the long deep dive
             | about DNA damage/repair/what the heck is happening in the
             | disparity between repairing damage for reproduction vs the
             | everyday repair, etc...)?
        
               | xiphias2 wrote:
               | You're half right, they are only resetting epigenetics
               | (for example DNA methylation that is important in cell
               | specialization), not DNA.
               | 
               | Altos Labs being funded is both a blessing and a curse,
               | because it funded the best researchers in this area with
               | hundreds of millions of dollars (5-10x their salary in
               | what they were making as university professors), but
               | since it was founded, there are much less publications
               | available.
        
               | [deleted]
        
             | timmg wrote:
             | > By far the most important thing in anti aging that checks
             | all boxes is excercise and getting nutrition right (no
             | excess fat).
             | 
             | Do you mean "don't eat excess fat" or "don't have excess
             | fat on your body"? It's not clear to me from the context.
        
               | inciampati wrote:
               | Second probably.
        
             | ben7799 wrote:
             | I think the important thing is to concentrate on the diet
             | and exercise and not sit around living an unhealthy
             | lifestyle and hoping to get on one of these drugs that is
             | possibly not that great anyway or has some serious side
             | effects you could end up with.
             | 
             | It's pretty obvious older people who have kept their
             | fitness (cardio & strength, not just one of the two) up and
             | their weight down their entire lives have profoundly higher
             | quality of life.
             | 
             | That requires a totally different lifestyle from the
             | standard "geek lifestyle" though.
        
               | tysam_and wrote:
               | Very much so, I think it's about healthspan rather than
               | lifespan for many people.
               | 
               | Hopefully we can improve that. Many people would be much
               | more okay with feeling great up until an old age, have a
               | few weeks of infirmity, and then pass away rather than
               | the multiple decades of gradual decay that we have now.
               | 
               | Not that that's necessarily entirely realistic or
               | possible, but it would be nice, if it is a possible thing
               | indeedy.
        
           | tysam_and wrote:
           | Creatine for brain health is unbelievably good too IIRC
           | (don't quote me on it though, please! ;P)
           | 
           | One of the hard parts of aging stuff is how nonlinear it is.
           | A lot of the good drug treatments seem to be short
           | term/cyclical, along with significant lifestyle
           | modifications.
           | 
           | In addition to what the other commenter said, I've heard of
           | OMAD and having a strong community/having a purpose or
           | something to do as another strong factor in longevity, in the
           | 90-100+ year olds in Japanese community for example. I can't
           | remember if OMAD was correlated to that community or a
           | different study, however.
        
             | GordonS wrote:
             | Can you say some more about brain health, like how much
             | creatine to take, what the expected benefits are, please?
        
               | tysam_and wrote:
               | Here is a good article, I think my favorite part is the
               | paragraph containing reference #146:
               | https://www.mdpi.com/2072-6643/14/5/921
        
           | irthomasthomas wrote:
           | Metformin.
           | 
           | Research in humans suggests that metformin can impact
           | mortality. A meta-analysis published in 2017 that included 53
           | different studies concluded that metformin reduces all-cause
           | mortality and diseases of aging, independent of its effect on
           | diabetes.
           | 
           | Also, combinations of Metformin, rapamycin and resveratrol,
           | and NMNs.
           | 
           | Davis Sinclaire is probably the leading expert on those, now.
           | He is professor of genetics at Harvard.
           | 
           | https://youtube.com/watch?v=bRWT7hVgwuM
        
             | tysam_and wrote:
             | It looks really promising. However, there are some growing
             | concerns I believe that link it with mitochondrial
             | dysfunction as well, if I recall correctly. Hopefully
             | that's not the case, but it's a developing story. (It does
             | reduce exercise output as well if someone is an athlete and
             | cares about hat, but since it does mimic exercise in a way
             | on a cellular level, that's to be expected I guess). :'(
        
               | irthomasthomas wrote:
               | There's always exceptions in popular medicine. No doubt a
               | small minority of people get no benefit, or may even be
               | mildly harmed by the medicine. But Metformin, in
               | particular, is one of the most popular drugs in the
               | world, and it's strong safety profile is well
               | established. "All-cause mortality is lower in people on
               | Metformin". So, I don't think there will be any big
               | surprises found in its safety, but maybe we'll find that
               | a certain minority of the population aren't suited for
               | it.
        
               | phkahler wrote:
               | Mitochondria need proper care too. I take iodine and
               | magnesium for asthma (which is cured) and I hear iodine
               | is also go for mitochondria, which might explain why it's
               | good for so many things.
        
             | safety1st wrote:
             | This one is really interesting, thanks. I think it's the
             | closest any mentioned substance comes to passing the
             | "creatine test" (for whatever that test is worth; I just
             | made it up).
             | 
             | (A) The body of research is, in general, large and
             | uncontroversial.
             | 
             | (B) The safety profile is good. The benefits for diabetics
             | are certainly large. Probably no drug has been studied for
             | anti-aging effects as extensively as creatine has been for
             | fitness applications, so I'm not sure anything can fulfill
             | that criteria. But it seems like the present research on
             | metformin supports a variety of positive effects for non-
             | diabetics with more on the way.
             | 
             | (C) I wouldn't know whether the majority of people who are
             | serious about anti-aging use it but it does get mentioned a
             | lot.
             | 
             | Pretty positive endorsement overall!
        
             | loeg wrote:
             | Worth pointing out that Metformin has a host of unpleasant
             | and common side effects. E.g., here's 40% of type 2
             | diabetics not adhering to the prescribed dosing protocol: h
             | ttps://joppp.biomedcentral.com/articles/10.1186/s40545-022-
             | ...
             | 
             | > A number of studies assessing adherence to diabetes
             | medications in patients with type 2 diabetes have reported
             | that metformin has the lowest adherence rates when compared
             | with other OAAs.
        
               | pazimzadeh wrote:
               | Is it known what the mechanism is for metformin's effect
               | on longevity?
               | 
               | If it's due to its ability to reduce blood glucose
               | levels, then berberine may be another way to get a
               | similar effect.
               | 
               | Berberine stimulates glucose transport through a
               | mechanism distinct from insulin
               | 
               | https://www.sciencedirect.com/science/article/pii/S002604
               | 950...
               | 
               | Efficacy of Berberine in Patients with Type 2 Diabetes
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/
               | 
               | It also lowers cholesterol
               | 
               | Berberine is a novel cholesterol-lowering drug working
               | through a unique mechanism distinct from statins
               | 
               | https://www.nature.com/articles/nm1135
               | 
               | But pure berberine is not absorbed very well in the
               | intestines, so you need to buy a good formation for it.
               | 
               | Enhancement of sodium caprate on intestine absorption and
               | antidiabetic action of berberine
               | 
               | https://www.ncbi.nlm.nih.gov/pubmed/20237966/
               | 
               | Amorphous solid dispersion of berberine with absorption
               | enhancer demonstrates a remarkable hypoglycemic effect
               | via improving its bioavailability
               | 
               | https://pubmed.ncbi.nlm.nih.gov/24607213/
               | 
               | The best thing might be to cook with barberries:
               | 
               | https://thecaspianchef.com/2020/01/18/zereshk-polo-
               | saffron-b...
        
           | m463 wrote:
           | Eating a calorie-restricted diet (fasting must be part of
           | this).
        
             | snvzz wrote:
             | Intermittent fasting and eating keto rather than carbs.
             | 
             | Health aside, it is hard to stress how much better I feel
             | on ketones, relative to carbs.
        
           | scythe wrote:
           | >Is there anything similar in the science of anti-aging?
           | Where (A) The body of research is large, well established,
           | and mostly uncontroversial; (B) The benefits and safety
           | profile are good; (C) The majority of people who are serious
           | about this stuff use it/take it/do it.
           | 
           | The sodium/potassium ratio, and particularly keeping it
           | smaller. The top answer right now is "nutrition", but that's
           | a hairball, and the Na/K is a bright spot that gets left out
           | of the discussion precisely because it is much less
           | controversial than the endless debate over macronutrients and
           | staples. The sodium/potassium ratio has effects on:
           | 
           | hypertension: https://onlinelibrary.wiley.com/doi/abs/10.1111
           | /j.1440-1681....
           | 
           | stroke/CVD: https://bmjopen.bmj.com/content/6/7/e011632.short
           | 
           | bone density:
           | https://academic.oup.com/jcem/article/87/5/2008/2846608
           | 
           | chronic kidney disease:
           | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047877/
           | 
           | and even such seemingly unrelated conditions as depression: h
           | ttps://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy..
           | .
           | 
           | and age-related cognitive decline: https://www.sciencedirect.
           | com/science/article/pii/S258979182...
        
             | Woberto wrote:
             | But where can we get potassium from?? I feel like when I've
             | looked, it's harder to come by than other vitamins/minerals
        
               | scythe wrote:
               | In general, potassium is found in fruits and vegetables.
               | It has to be spread throughout the day, because high
               | quantities of potassium at once have a laxative effect.
               | The highest concentrations are found in some vegetable
               | concentrates -- the densest source in your cabinet is
               | probably tomato sauce. It is present in milk and yogurt
               | but not in cheese.
               | 
               | Potatoes and other starchy vegetables like squash and
               | plantains have significantly more potassium than grains,
               | but it's not necessary to completely give up grains. I
               | usually put a 50/50 potassium/sodium ("Lite") salt on the
               | oatmeal or grits I make for lunch (work requires speed),
               | but I don't bother with it otherwise.
        
         | TeaBrain wrote:
         | There may be better anti-aging drugs that have yet to be tested
         | or discovered, but Rapamycin currently has the best data
         | backing it up. It is the only drug which has consistently
         | increased both median and maximum lifespan across organisms,
         | for both males and females, across many trials. It has also
         | been shown to increase lifespan when given to organisms after
         | they have reached their middle age, which is not common.
         | 
         | The Interventions Testing Program (ITP) by the NIH, which has
         | been testing substances for their effects on lifespan for over
         | 15 years, is regarded as the gold standard for testing possible
         | lifespan increasing substances. Rapamycin has outperformed
         | every other substance they have tested, by a wide margin. There
         | is only one other substance they have tested that has shown a
         | median and maximum lifespan increase, for both females and
         | males, that being acarbose. The greatest lifespan increase
         | observed in any of the trials was seen with the combination of
         | rapamycin and acarbose.
         | 
         | All of the substances that NIH ITP have tested with their
         | results listed, as well as the interventions they are testing
         | now: https://www.nia.nih.gov/research/dab/interventions-
         | testing-p...
         | 
         | List of the substances they have tested with charts showing the
         | relative increase in lifespan:
         | https://phenome.jax.org/projects/ITP1
        
         | reducesuffering wrote:
         | They're recommending Nicotinamide Riboside which has been
         | implicated in increasing cancers.
         | 
         | My heuristics researching supplements, nootropics, longevity,
         | are that the lab-created substances are more often than not,
         | new and poorly studied, leading to eventual realization of more
         | harm than they treat. Most recent, to me, was Alpha-GPC causing
         | strokes.
        
           | xk_id wrote:
           | That's not very accurate. It wasn't implicated in actually
           | causing cancers. Tumour cells happen to have a high demand
           | for NAD+, and NR provides them with that. So, if you already
           | have tumours, NR will accelerate their growth. However also
           | if you have had cancer recently and even if there are no more
           | detectable signs, it is still possible for some tumour cells
           | to be present; in that case NR is also risky. But if you are
           | healthy, NR is not a carcinogen and any risk of stimulating
           | the odd tumour cell is probably offset by the benefits NR
           | provides to the immune system.
        
             | tysam_and wrote:
             | This is an excellent direct summarization of NR<->Cancer.
             | Thank you for sharing this, I greatly appreciate it. <3 :)
             | 
             | Not everyone needs NR necessarily (or any of the other
             | forms), but it does seem to get more important as we get
             | older and our ability to manufacture NMN goes down (IIRC
             | that's the main target that's limited here?)
        
             | onlyrealcuzzo wrote:
             | I think you're assuming the body doesn't form small tumors
             | and destroy them naturally.
             | 
             | If something else is helping the tumors grow faster than
             | the body can kill them naturally - then it's going to
             | result both more severe tumors AND more tumors in general
             | (as we discover them, since we usually don't know about
             | tumors that form and get destroyed by the body naturally).
        
               | xk_id wrote:
               | Covered in the last sentence.
        
             | thewataccount wrote:
             | IIRC isn't NAC similar? It's not carcinogenic itself, but
             | the benefits it provides also extend to the cancer cells?
        
               | garganzol wrote:
               | NAC is a glutathione precursor. It is both anti- and pro-
               | cancer. It is anti-cancer in a sense that glutathione
               | reduces the risk of getting cancer in the first place. It
               | is pro-cancer in a sense that it reduces the power of
               | immune response due to reduction of the amount of
               | produced ROS, which may theoretically lead to a faster
               | cancer spread.
               | 
               | So yeah, they both are kind of similar in that dimension.
        
           | garganzol wrote:
           | Cancer thrives on any kind of NAD source, not specifically
           | Nicotinamide Riboside. Even milk poses a risk of increased
           | tumor growth (it contains NAD, a lot of it). But it only
           | applies to those who have the ongoing oncology in the first
           | place, so... blaming NR for causing cancers is probably a
           | misfire.
        
           | tysam_and wrote:
           | Like all things, it's about balance. In this case, NR was
           | recommended as a cheaper alternative to NMN, I believe,
           | though one can take Nicotinamide and Ribose separately IIRC
           | (ribose is expensive either way, lol. Tastes great though, a
           | very, very fancy sugar indeed).
           | 
           | As far as cancer goes, basically half of the solutions here
           | will cause cancer. That doesn't mean they're bad. Anything
           | involving the body is extraordinarily nonlinear, so
           | extrapolation is extremely hard in a variety of
           | circumstances. You can find a study involving almost
           | everything you consume and take linking it to a variety of
           | things, it's just whether or not it's relevant to people in
           | the doses and in the duration that they take them.
           | 
           | Especially on the cancer side of things, that's just a very
           | delicate matter to be handled. Cleaning things up in theory
           | should reduce the risk of cancer overall, even if ingredients
           | on their own at some dose could cause issues.
           | 
           | A lot of these compounds have been around for or have been
           | studied for 40-50 years or so. Some of the long-term effects
           | are harder to pinpoint, but I'd be careful in seeking too
           | much caution (in the same way I'd encourage someone not to go
           | headlong throwing stuff into their bodies for no good
           | reason). It's really easy to find nonlinear red lights for
           | almost anything in medicine, in my (albeit limited) personal
           | experience.
        
             | analognoise wrote:
             | This sounds like the chemical reasoning of homeopathy to
             | me.
        
               | tysam_and wrote:
               | Not necessarily.
               | 
               | I can give an analogous example.
               | 
               | Lengthening telomeres is a naive strategy some chase for
               | longevity. You can think of telomeres as aglets for DNA
               | -- they shorten as you get older. So inhibiting that
               | shortening is good, right?
               | 
               | Well, that does extend life, in a way, but it also slows
               | down DNA repair and makes that a harder thing to access,
               | because now damaged DNA has longer end-caps on it too.
               | 
               | So of course a few years after the whole "Just take
               | telomere lengtheners!" headline wave, another headline
               | wave of "Telomere lengtheners actually can worsen aging!"
               | is a decent followup to expect (something like this
               | happened IRL IIRC).
               | 
               | You can make a similar analogy with stem cells and a
               | limited stem cell pool (do you deplete the pool early,
               | assuming it no longer regenerates at this point, for a
               | boost of apparent vitality, or ration it over the course
               | of a lifetime?)
               | 
               | Homeopathy on the other hand assumes a bizzare, quantum-
               | like "memory" in molecules that has not been shown to be
               | accurate by science, but excels as being a placebo
               | effect.
               | 
               | These are quite different phenomena. It's another way of
               | saying "the dose makes the poison", though in this case,
               | it's "the dose has varying and highly state-dependent
               | effects within a strongly chaotic dynamical system".
        
             | reducesuffering wrote:
             | I think most people would agree that taking carcinogens
             | will more likely reduce your lifespan than the possibility
             | of significantly extending it.
             | 
             | For now, I'd rather bet on very clean air, very clean
             | water, fasting, organic vegetables, green tea, omega 3 fish
             | oil, well monitored sleep, and lots of exercise for
             | longevity.
        
               | tysam_and wrote:
               | That does feel like an overly simplistic argument. Once
               | again, lots and lots of things feed cancer, it's not as
               | simple as that. There's also a big 'might' clause, which
               | means it's something that's going to take time to
               | understand. For example, IIRC, the role that NR might
               | play in cancers is that it's a very accessible food
               | source for them. However, compared to other factors, this
               | might fade into the woodwork, especially if for example
               | it's used as part of a protocol that lowers the chance of
               | cancer (or at the very least, all-cause mortality) longer
               | term. Ideally, at least.
               | 
               | Maybe an analogy to communicate the concept is that it is
               | like putting a car up on jacks and taking out parts to
               | repair another part. It's possible that it is not where
               | you are long-term, or ideal to do extremely frequently,
               | but it's important to keep the thing maintained and
               | running.
               | 
               | That said, I agree very much on your last sentence as one
               | of the best "simple" routines to get bang for the buck.
               | My thoughts would be weight lifting specifically,
               | chamomile tea at night (apigenin is something else), as
               | well as some broccoli sprouts for NRF2 in there. Other
               | than that I think that's probably the index fund-like
               | strategy to longevity, so we're definitely on the same
               | page there. :D :thumbsup:
        
         | voldacar wrote:
         | Is there anything in the works that can break down lipofuscein
         | or advanced glycation endproducts? Those always seem under-
         | discussed.
        
           | tysam_and wrote:
           | I try to keep up with the AGE breaker development, I thought
           | there were at least one or two labs/companies trying to
           | develop them.
           | 
           | I think IIRC that the crosslink breakers (referring to AGE
           | above for those OOTL) mainly struggle from delivery being
           | difficult? Because many of the AGEs we care about can end up
           | in some bizzare, hard-to-reach places? I think?
           | 
           | I don't think this is directly related but there was one
           | therapy for cellulite that just had an enzyme that dissolved
           | collagen. I just learned that they (sadly, in the long run
           | for the research field in that area) had to shutter that
           | after only two years or so, apparently due to the bruising
           | and discoloration of skin long term
           | (https://investor.endo.com/news-releases/news-release-
           | details...). I guess I can only feel so bad as they were
           | marketing pretty heavily to people who were rich enough to
           | pay for the cosmetic surgery out of pocket, and were as well
           | in a category of middle-aged "luxury" buyers (from the
           | official website -- I don't think the wayback machine will
           | show the pictures [warning, very butt focused], but perhaps
           | for the better, the saved version has the desktop and mobile
           | transcript. Confetti for a medical drug advertisement
           | website. Incredible: https://web.archive.org/web/202101241426
           | 05/https://www.qwo.c...)
           | 
           | Lipofuscein I'd love to learn about, I have not heard of that
           | before.
        
             | voldacar wrote:
             | Interesting stuff, glad to see that the research is
             | continuing in this area. I'm thinking about experimenting
             | with topical alagebrium just to see if it does anything. I
             | recall a study in mice that found a very significant effect
             | on skin wrinkles in aged animals.
             | 
             | And it's lipofuscin, I mistyped it. Basically oxidized junk
             | molecules that never seem to get broken down and just
             | accumulate within the cell with age. Interestingly,
             | piracetam seems to have a positive effect on this in rodent
             | brains.
        
         | [deleted]
        
         | Mistletoe wrote:
         | 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 wrote:
           | 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 wrote:
             | That's about the distribution one could expect for placebo
             | too.
        
               | tysam_and wrote:
               | Could be. Longecity I've found to be an odd mix of people
               | who are rather combative about whether things work or not
               | and who are way too in-depth (in a good way) about their
               | personal experiences about what worked or not.
               | 
               | At the very least, it's intriguing and out of all of the
               | thousands of pages of medical literature I've read over
               | the past half decade or so it's been one of the more
               | interesting sagas to follow.
        
               | drBonkers wrote:
               | I have an intuition that if we are to find a solution it
               | is more likely to first sprout from fringe
               | experimentation, such as from Longecity, than the
               | academy.
        
       | starchild_3001 wrote:
       | 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 wrote:
         | There are quite a few studies ongoing in '22 and '23.
         | 
         | https://www.rapamycin.news/t/rapamycin-clinical-trial-update...
        
         | cornholio wrote:
         | 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.
        
           | amts wrote:
           | 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.
        
           | tysam_and wrote:
           | 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.
        
       | schmichael wrote:
       | 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.
        
         | djmips wrote:
         | We all want to live long enough to witness the singularity.
         | <wink>
        
         | bowsamic wrote:
         | To me it just signals a lack of emotional maturity
        
         | thriftwy wrote:
         | https://en.wikipedia.org/wiki/Trouble_with_Lichen
        
           | jazzyjackson wrote:
           | Thanks for that, never heard of it before - there is a 90 min
           | radio adaptation archived here:
           | 
           | https://archive.org/details/john-wyndham-trouble-with-lichen
        
         | jimbob45 wrote:
         | To be fair, the other most likely source you'd receive anti-
         | aging news from, r/science, is hands down the worst moderated
         | community on the internet and I wouldn't put it past them to
         | bury such news by their own whims.
        
         | George83728 wrote:
         | I regularly see anti-aging discussion/news here and on 4chan's
         | /sci/ board (aka the flat earth and electric universe debate
         | forum.) Make of that what you will.
        
         | Dylan16807 wrote:
         | Do you see more discussion of anti-aging on HN than you see
         | discussion of major diseases?
         | 
         | I don't see more of it. And I think it's fair to talk about
         | aging as much as cancer, for example. They're both very
         | difficult fights to claw back months or years, but we can
         | figure out how to slow the progress and cure specific
         | instances.
         | 
         | If we could extend life expectancy by two years that might beat
         | covid in impact. Isn't that worth significant research and
         | discussion?
         | 
         | It's not just people idly wanting to live a million years.
        
           | snvzz wrote:
           | >And I think it's fair to talk about aging as much as cancer,
           | for example.
           | 
           | I agree with the underlying argument, but I must note: Cancer
           | gets more likely with age, and the mechanisms that enable it
           | are considered one of the (few) groups by which aging is
           | characterized.
           | 
           | All these groups are co-morbid, so any progress in un-doing
           | the damage of aging will also help with cancer.
        
         | dsco wrote:
         | You think anti aging obsession is wild here? Wait until you see
         | the anti crypto obsession
        
           | Gigachad wrote:
           | Go out on the street and ask the average person what they
           | think about crypto and NFTs.
        
         | aaron695 wrote:
         | [dead]
        
         | cowmoo728 wrote:
         | There are a lot of men in tech with lots of money, engineering
         | expertise that they believe will carry over to biology, and a
         | fear of becoming old and irrelevant.
        
           | ShamelessC wrote:
           | Ding ding ding.
        
         | timwaagh wrote:
         | I don't know man my parents just spent the first few years of
         | their early retirement caring for my grandma who is now in the
         | final phase. It's not like you just won't be there one day. It
         | also costs others a lot of time and effort, money et cetera.
        
         | rsynnott wrote:
         | The odd thing is, HN is also obsessed with early retirement.
         | You'd think people would've learned the lesson of One Foot in
         | the Grave.
        
         | bawolff wrote:
         | HN has always had some science content not just tech. Articles
         | about fusion and batteries get promoted here often. If all your
         | other sources are pure software focused it would make sense you
         | dont see aging there.
         | 
         | As for the actual topic. Lots of people talk about fear of
         | death, and i am sure that plays a part. For me though, i think
         | its interesting because people have been trying to increase
         | longevity since forever and haven't succeded yet. There is
         | something fascinating about a problem everyone has tried to
         | solve but still isn't solved.
        
           | AnthonyMouse wrote:
           | The median lifespan is ~77 years but some people live to
           | ~115. That's quite a difference. Some of that may be genetics
           | but not all of it. The median person who dies at 95 is doing
           | something different than the median person who dies at 60.
           | The least we can do is find out what.
           | 
           | And maybe if we do, someone could live to be 130, or still be
           | in good health at 95.
        
         | henearkr wrote:
         | How are you going to learn all the essential Javascript
         | frameworks in time if you die before you reach your first few
         | centuries of age?
        
         | db48x wrote:
         | https://www.youtube.com/watch?v=jdCB9yE9Hcc
        
         | xarope wrote:
         | 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 wrote:
           | 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 wrote:
             | Such an educated audience. And brilliant too. Other
             | demographics can't hold a candle to how smart and also cool
             | HNers are.
        
               | analognoise wrote:
               | You forgot attractive; nothing but raw sexual energy from
               | this bunch.
        
         | sanxiyn wrote:
         | I do not get why you do not get the appeal. Do you want to die?
        
           | silisili wrote:
           | Not OP, but my opinion is that I want to die when I'm
           | supposed to, and I want everyone else to also. Time is the
           | great equalizer, and the well to do's should not be able to
           | purchase more.
           | 
           | The last time I wrote this opinion, I was met with everything
           | from 'just kill yourself' to 'quit trying to control my
           | life.'
           | 
           | Funny bunch here.
        
             | snvzz wrote:
             | That's fine, you and your ilk can get old on your own,
             | suffer from the degradation of health and consequently
             | quality of life caused by aging, and eventually die from
             | old age, we won't stop you.
             | 
             | The rest of us will support the relevant research, and use
             | the results to remain young or to be young again, possibly
             | lasting for millennia.
        
               | account-5 wrote:
               | Sounds like hell on a dying planet where more people keep
               | coming and no one leaves.
               | 
               | (Dying from the point of view of being about to sustain
               | human life)
               | 
               | Unless of course we have magically conquered space travel
               | too.
        
               | vineyardmike wrote:
               | > Unless of course we have magically conquered space
               | travel too.
               | 
               | If everyone sticks around, they can help solve the
               | problem. If people don't die, maybe they'll be forced to
               | care for the planet instead of spoiling it for the next
               | group.
        
               | account-5 wrote:
               | Lot of ifs and maybes there. And a lot of faith that the
               | human race can actually pull together to do that.
        
               | snvzz wrote:
               | It beats giving up on mankind from the get-go.
        
               | silisili wrote:
               | I have a feeling we'll both be worm food by 80 or 90. The
               | difference being my ilk had a better appreciation for
               | time, while yours thought they'd live forever.
        
               | Dylan16807 wrote:
               | Do you really think it makes that much difference, day to
               | day?
               | 
               | Because if better appreciation just means you're on the
               | right side of an argument that very rarely comes up, then
               | your life quality is the same.
        
               | somenameforme wrote:
               | Contrary to the person you're responding to, I think it
               | does make a large impact on the day to day. It's going to
               | drive very different philosophies of life. One obvious
               | embodiment of this would be on fertility. One who
               | ignores, let alone denies, their own mortality is going
               | to, on average, a different perspective on fertility than
               | somebody who accepts their own imminent mortality. And
               | these sort of things can often sort of snowball into
               | impacting many other issues in life, in very significant
               | ways.
        
               | silisili wrote:
               | Day to day, not at all. Just more generally. How many
               | times have we heard 'I wish I'd visited my X more before
               | they died.' Timelines and sense of mortality force you to
               | think about such things.
               | 
               | It's definitely not about taking solace in winning some
               | inane argument. I won't be celebrating my death, nor
               | yours, as some kind of win.
        
               | snvzz wrote:
               | You think the problem of aging cannot be resolved?
               | 
               | Aging has long been characterized. We understand in which
               | ways degradation happens, and no new ways have been found
               | for several decades. There aren't that many; They can be
               | tackled, one by one.
               | 
               | We have an assortment of tools today that weren't
               | available a mere 20 years ago, and it is our moral
               | imperative to do this research.
               | 
               | There's more people suffering from aging and the
               | conditions it does cause than any other health issue. All
               | of us will eventually degrade, suffer and perish if
               | nothing is done about it.
               | 
               | Improving the quality of life of our aging population by
               | supplementing the shortcomings of metabolism (and thus
               | un-doing aging) is the target.
               | 
               | Longevity would be a byproduct of this.
        
             | boomboomsubban wrote:
             | The dying part bothers me less than the aging. I'd be fine
             | dying at the "normal" age, but I'd rather do so with a
             | healthier body than my grandparents.
             | 
             | And telling other people when they should die is sorta
             | messed up. Ignore these anti-aging medications, should
             | people be cut off other medicines at a certain point?
             | What's the difference?
        
               | silisili wrote:
               | I've had all these arguments before, that I don't care to
               | have again.
               | 
               | > And telling other people when they should die is sorta
               | messed up
               | 
               | I'm not telling other people when to die! I'm thinking
               | more of a societal contract. Which in fairness, seem less
               | and less these days.
               | 
               | Like, if I go to the back of a queue, and see you going
               | to the front, and request you go to the back... I'm not
               | trying to control your life. I'm just asking you to
               | acknowledge and respect that we live in a society.
        
               | boomboomsubban wrote:
               | >I've had all these arguments before, that I don't care
               | to have again.
               | 
               | The arguenent of "I don't want to need help going to the
               | bathroom/eating?" Or "I don't want to have effectively a
               | two minute memory?" They're pretty solid arguments to me.
               | 
               | >I'm not telling other people when to die!
               | 
               | No, you want society to agree with you when people should
               | die. This societal contract already does not exist. Maybe
               | it'd be nice if it did, but you'd still need to answer
               | the question of "should I stop this person from taking
               | medicine because it's time for them to die?"
        
             | glerk wrote:
             | Our ancestors probably also had to put up with people like
             | you trying to prevent them from making fires because night
             | is the great equalizer and everyone should sleep when it's
             | dark or some other nonsense.
             | 
             | I feel miserable just trying to imagine why a person would
             | think this way. I'm grateful I don't have this kind of
             | psychology.
        
             | midoridensha wrote:
             | >Time is the great equalizer, and the well to do's should
             | not be able to purchase more.
             | 
             | The entire medical (and dental) profession is all about
             | keeping you from dying when you're "supposed to". You're
             | supposed to die in your teenage years of a tooth infection,
             | or in your 30s or 40s of cancer, or any random age of an
             | injury.
             | 
             | People in rich countries live much longer (and healthier)
             | than people in poor countries because of access to modern
             | medicine.
             | 
             | So apparently you think people shouldn't have access to any
             | medical services?
        
             | Nursie wrote:
             | You're entitled to have opinions about your own life. When
             | you start using your values to try to decide how long I
             | should live mine... this is why you get hostile reactions.
             | 
             | > Time is the great equalizer
             | 
             | Yes, totally, we all get to live exactly the same amount of
             | time, so it's perfectly fair. Also that fixed term life
             | deal is the perfect amount of time by definition, so we
             | should never, ever try to change it.
        
               | silisili wrote:
               | Yes, your reaction was covered under the 'quit trying to
               | control my life' clause. Not sure what else is being
               | added here.
        
               | Nursie wrote:
               | > Not sure what else is being added here.
               | 
               | A challenge to your assumption that there is an implied
               | system and that said system is somehow fair in its
               | current state. It's nonsense.
        
               | silisili wrote:
               | Would you agree that for every year added to your life, a
               | year should also be added to all those in third world
               | countries?
               | 
               | My main argument is against the wealthy buying time that
               | others cannot. This is why I'm not against say,
               | penicillin and such.
               | 
               | If you feel that is a bad argument, please explain why.
               | If you feel it's fair, then I think we may agree. I'm not
               | against humanity living longer, I'm against some select
               | few doing so.
        
               | Nursie wrote:
               | I don't disagree with that at all, in principle.
               | 
               | "I should get to live longer and everyone else can rot"
               | would be a particular sort of evil.
               | 
               | However what I don't agree with is going from there to
               | "unless everyone can have it, noone can". An awful lot of
               | medicine is not (yet) available to everyone in the world,
               | and while I think it should be, and we should work
               | towards every last human being having access to free,
               | socialised healthcare of the highest quality, you won't
               | find me calling for denying cancer treatments to those in
               | wealthy nations because other nations can't foot the
               | bill.
        
               | silisili wrote:
               | Well, the other side of the coin is whether those folks
               | even want to live longer.
               | 
               | We have gotten so used to being generally blind to
               | essentially slave labor to support our lifestyles. Is it
               | fair if we double our lifespan while those stuck in
               | poverty making our products don't, or perhaps don't even
               | want to?
        
               | Nursie wrote:
               | I don't think very much is fair about anything in that
               | picture, but I also don't think we should hold back
               | advances or treatments while we work that out, nor do I
               | think that it's particularly useful to relate those two
               | phenomena specifically, you could as well say "Is it fair
               | we use jet-skis while those stuck in poverty making our
               | products have such a poor quality of life? Is it fair to
               | use iphones while those stuck in poverty making the
               | iPhones have such a poor quality of life?", and to be
               | honest I'm slightly inclined to say "no" to that last
               | one...
               | 
               | Significant longevity treatment is likely to be highly
               | disruptive to our society in many ways, but I don't think
               | that we should either fall for the fallacy that we can
               | accurately predict those ways, nor succumb to the idea
               | that we won't or can't adapt positively.
        
           | rocket_surgeron wrote:
           | It doesn't bother me.
           | 
           | Every single one of my ancestors for the last 3.5 billion
           | years has died. It is part of existence.
           | 
           | 50, 60, 100 more years? Great! Then I can pile on knee, hip,
           | back, and wrist regeneration surgeries. Then extensive
           | therapy to keep my brain from degrading. Also new teeth and
           | corneas. Oh and the heart is going to need a lot of work if
           | it starts beating for twice as long as it was designed to.
           | Plus constant maintenance for the skin as it soaks up an
           | entire second lifetime's worth of UV.
           | 
           | Just a never-ending cycle of expensive, likely painful, time-
           | consuming all-consuming patches on the body to delay the
           | inevitable.
           | 
           | Just kill me already.
           | 
           | Maybe eventually they'll find a path to immortality.
           | 
           | That would be even worse. I imagine the joy would drain out
           | of sunsets if you've seen a billion of them, with them being
           | as noteworthy as every time your eye blinks.
        
             | Gigachad wrote:
             | What if its not constant patches and repair work, but
             | something that slows the degradation entirely so you end up
             | with less health issues up until the point you get cancer
             | and die anyway. But you enjoyed more of that time fitter
             | and healthier.
        
             | powerapple wrote:
             | I would be very happy if my body can stay young and not
             | necessarily live longer. That's what anti-age means right?
             | Not pro-long your life necessarily, but to live younger, so
             | I don't have to care about my knee problem when exercise.
        
             | midoridensha wrote:
             | >50, 60, 100 more years? Great! Then I can pile on knee,
             | hip, back, and wrist regeneration surgeries. Then extensive
             | therapy to keep my brain from degrading. Also new teeth and
             | corneas.
             | 
             | >Just a never-ending cycle of expensive, likely painful,
             | time-consuming all-consuming patches on the body to delay
             | the inevitable.
             | 
             | So I take it you never visit a doctor or dentist? After
             | all, going to the doctor to get that mole checked for
             | cancer, or getting your teeth drilled to prevent an
             | infection that kills you is unnatural.
        
             | vidarh wrote:
             | Anti-aging by necessity also means solving the common
             | causes of death and your body falling apart, not just
             | letting them happen but somehow preventing them from
             | killing you.
        
             | pengaru wrote:
             | It's more about "die young, as late as possible" than live
             | forever
        
             | Nursie wrote:
             | > I imagine the joy would drain out of sunsets if you've
             | seen a billion of them, with them being as noteworthy as
             | every time your eye blinks.
             | 
             | So you can imagine that rather than see another sunset,
             | you'd die?
             | 
             | You can imagine a state of being where you become so jaded,
             | so incurious, that nothing can pique your interest any
             | more, that interpersonal relationships would be better off
             | terminated with biological death than continued, that
             | learning, travel, discovery all lose their meaning and
             | value?
             | 
             | Honestly, as with many of these comments, I feel it says
             | more about your present life than those who would like to
             | live longer or indefinitely.
             | 
             | And I certainly know people in their 70s who are not ready
             | to settle down and be fitted for a coffin yet, even if
             | their bodies are starting to seriously disagree. I don't
             | imagine they would turn down the chance of a few more
             | decades of relative fitness.
        
           | steve_adams_86 wrote:
           | I don't think I'm important enough for it to matter, and I'm
           | fairly sure the fact I will die is a significant component of
           | what makes the brief time I have so valuable.
        
             | mitthrowaway2 wrote:
             | Is your life more valuable the briefer it is?
        
               | ptsneves wrote:
               | If 1/x where x is the current age, then yes. I say it as
               | a joke but makes me think why more mundane experiences on
               | my childhood stuck more than profound ones on later life.
        
             | heroiccocoa wrote:
             | An enormous amount of resources are wasted on treating
             | specific, often rare, individual age-related conditions
             | that doesn't efficiently transfer to other conditions.
             | Clearly, people are hurting and it'd a net positive to
             | society to treat the single underlying cause, and save the
             | resources expended on everything else, for an equal if not
             | improved overall health outcome.
             | 
             | Even if you don't consider yourself important to the world,
             | surely you are important to yourself. At least I as an
             | atheist consider my limited time alive here-- conscious and
             | healthy-- to be infinitely valuable to me _personally_ as
             | it 's really all that I have. And I think if your life
             | isn't valuable to you in the same way, there's something
             | wrong. Hence, extending it is a worthwhile goal.
             | 
             | Longevity research is difficult and it's not as if a
             | breakthrough improving our lifetime by an order of
             | magnitude is around the corner. So, I see little risk in
             | ambitious research that'll probably only yield humble
             | results anyway, at least until we're reaching 200 years
             | old.
        
               | justinclift wrote:
               | > surely you are important to yourself.
               | 
               | Depends on how depressed a person is I guess. ;)
        
               | steve_adams_86 wrote:
               | > Even if you don't consider yourself important to the
               | world, surely you are important to yourself. At least I
               | as an atheist consider my limited time alive here--
               | conscious and healthy-- to be infinitely valuable to me
               | personally as it's really all that I have.
               | 
               | I agree with this completely, so long as it doesn't
               | actually cause problems for younger people born into the
               | world. At the moment it's arguably a good thing that we
               | die and let new generations have their shot at things.
               | I'm only 37 and already excited to see what people in
               | their teens manage to accomplish before I die. By the
               | time the they're full swing and doing cool stuff, I'll
               | probably be looking for my keys for a car I haven't owned
               | for 20 years in a bingo hall. No one will need more of
               | me.
               | 
               | Fundamentally though I believe our time is rarely spent
               | as well as it could be, and fixing that might be best to
               | come first. Should I live longer if I don't cherish it?
               | Should I want more days when I've admittedly wasted many?
               | Perhaps the best thing I could do is learn to use the
               | time I have to its fullest.
               | 
               | And of course, I go to great lengths to protect my health
               | and lifespan -- I want to live as long as I reasonably
               | can, and I want to be able to enjoy it. I don't think for
               | a second that I should prolong that to any degree which
               | begins to hinder the opportunities and possibilities of
               | younger people, though. Maybe that sounds crazy. I just
               | don't think I matter more than another person, just like
               | me, wanting all the same opportunities in their own life.
               | I guess I don't believe old people should be in the way
               | of young people fully living their lives.
               | 
               | As long as that's not happening, sign me up. Until then
               | I'd like to learn to use my time more wisely. On the
               | Shortness of Life totally transformed how I think about
               | longevity and lifespan extension in general. It seems to
               | pale in importance compared to the practice of living
               | better to begin with.
        
           | ptsneves wrote:
           | For me the anti aging, immortality thing is funny because I
           | think it has been solved for most species: it is called
           | reproduction. Actually surviving is reproducing.
           | 
           | If anti aging proponents spent as much time trying to
           | reproduce and making sure their offspring were fit to
           | continue their bloodline with good education it seems to me a
           | good outcome. That is why the education of my children is
           | important: the imprint of intellect self after I imprinted my
           | bodily self in their genes.
           | 
           | One could argue, but "hey ptsneves your children are not you
           | thus you will unavoidably going to be eliminated from
           | existence". And I say, "it is ok and part of physical
           | existence. I accept it."
           | 
           | Evolution found it worthwhile to have sexual reproduction,
           | meaning clones are a bad fit for eco system disturbances.
           | 
           | Evolution also found it fit to restart the cycle from scratch
           | even if it meant an individual would lose experience or
           | ecosystem optimality. This is to protect again local optimae
           | , which is a great path to extinction.
           | 
           | The extent of these 2 premises is such that the apex predator
           | on earth reproduces sexually and has a limited life span.
           | Maybe that is survival bias but I think there are good
           | causation ideas behind them.
           | 
           | With the above if I really want to be immortal and have my
           | legacy preserved robustly I should use the current system:
           | reproduction with a good emphasis on descendant upbringing
           | and according to my experience. Again, even if I am great in
           | my current eco system I do not presume this experience will
           | work with eco system disturbances, so I accept evolutionary
           | bargains and have children with a partner I believe will
           | fulfil my bodily destiny the most resilient way possible.
           | 
           | I even wanted to start a religion where propagation of one's
           | self through dedication to offspring and community is
           | central. I am tired of a society ruled by geriatric
           | concerns[1]. (I say this as mostly a joke of course, I have
           | more than enough work raising my children much less dabbling
           | in other peoples lives)
           | 
           | Ps: none of what I wrote invalidates improvements on
           | longevity. It is just that we already have a basic system for
           | propagation in time.
           | 
           | [1] I know extremely young demographics make for crappy
           | countries and quality of life.
        
             | emptyfile wrote:
             | [dead]
        
           | freehorse wrote:
           | This question/answer is the standard fallacious response to
           | anybody talking against the anti-aging current.
           | 
           | Some people may indeed prefer to die, some people may be
           | religious or whatever, but most people doing the criticism
           | just give extremely low prior probability to not dying due to
           | some technological/medical advance (during their lifetimes at
           | least), so they consider obsessing with something that is
           | virtually impossible for the hope that it will happen a waste
           | of time, of the finite life they have.
           | 
           | Then it boils down just to whether one is curious about it,
           | or is curious about any other X subject.
        
           | jones6ofMont wrote:
           | [dead]
        
           | an-honest-moose wrote:
           | It's not about not wanting to die. It's about death being
           | inevitable. Everything dies, or breaks down, or decays.
           | That's just how the universe works.
           | 
           | The best you'll get is extended life, and that's never going
           | to be enough - there's always going to be someone trying to
           | push that limit out a little further. IMO, what matters more,
           | and what some folks here have brought up, is more healthy
           | years. I think wanting to be fitter and healthier in old age
           | is pretty uncontroversial, but the problem is that it gets
           | rolled up with immortality, because getting to say "We
           | conquered death" would be way sexier than saying "We extended
           | good living by a decade or two (and that's being
           | optimistic)".
           | 
           | Immortality has been, and always will be, a fantasy. Better
           | that those resources go to something more productive, like
           | healthcare.
        
             | carlmr wrote:
             | Death is the evolutionary proof that sometimes you need to
             | shut down legacy systems because maintenance has become
             | painful, the system has accumulated too many workarounds,
             | and a rewrite is in order.
        
             | Nursie wrote:
             | > Everything dies, or breaks down, or decays. That's just
             | how the universe works.
             | 
             | Sure, that's entropy, but that's only necessarily true at
             | the level of the whole system, energy inputs can and do
             | reduce local entropy.
             | 
             | > The best you'll get is extended life
             | 
             | Sounds good, let's start there. 'True' immortality may or
             | may not be a pipe dream, but it doesn't matter if it is.
             | Almost nobody is talking about living absolutely forever,
             | but looking at ways in which greater longevity can be
             | achieved. I'd bite your hand off for another couple of
             | decades on top of whatever my current 'allocation' might
             | be, I don't give a crap if we've "conquered death" or not,
             | but if we can find ways to give the average person more
             | time, that seems like a win.
             | 
             | > Better that those resources go to something more
             | productive, like healthcare.
             | 
             | How is this not healthcare?
             | 
             | There seems to be this backlash against any talk of life
             | extension, that other things matter more, that it's somehow
             | frivolous, or just morally wrong to seek to live longer. It
             | feels to me entirely arbitrary as we already use all sorts
             | of interventions to help people live longer, and to be
             | healthier for more of that time. This is good and wise and
             | virtuous. But some folks seem to have this weird switch in
             | their heads when extending life gets mentioned, that
             | suddenly they're uncomfortable and the whole thing is not
             | to be discussed by preference.
             | 
             | And I wonder if it's because they don't want to admit to
             | themselves or others that they are terrified, but have
             | rationalised away their fear as "meant to be, can't be
             | changed". Such talk of extension makes them uncomfortable.
        
             | inglor_cz wrote:
             | Your post is a good example on how even highly educated
             | people need more education, how communication is an
             | important thing in science and how framing changes
             | perception of everything.
             | 
             | Anti-aging science is basically the most audacious
             | preventative program out there. It is not really about
             | "immortality" (even if this level of success were to be
             | reached, one can always kill themselves, no biology will
             | give you immunity to fast flying bullets), but an attempt
             | to prevent or at least delay onset of a host of chronic
             | diseases that are synonymous with aging.
             | 
             | "but the problem is that it gets rolled up with
             | immortality"
             | 
             | Then don't contribute to that problem by insinuating that
             | anti-aging is something different from healthcare. It is
             | not, it is literally about extending healthspan, at least
             | at this point. Rejuvenation means making people live longer
             | by improving their metabolism etc.; how it is _not_
             | healthcare in the best sense of the word (protecting
             | _health_ instead of treating already extant _diseases_ )?
             | 
             | "Everything dies, or breaks down, or decays."
             | 
             | And yet you can keep your room tidy for long decades even
             | if the entropy of the universe as such increases.
             | 
             | We have a lot of self-repair mechanisms, that is why we
             | live longer than our relatives like dogs and mice. "The
             | universe" does not dictate to us whether to get cancer or
             | not; some species (like whales) seem to be very resistant
             | to cancer and it is absolutely thinkable that we could
             | acquire this ability too, if we happen to learn enough
             | about metabolism. Etc. etc.
             | 
             | Human death at 80 isn't a result of laws of physics, any
             | more than murine death at 2,5. It is a case of biological
             | dysregulation that can possibly be fixed or at least
             | improved, much like we improved other things about
             | ourselves. Few of the HN crowd would proclaim wearing
             | glasses to fix your vision to be unnatural. What we are
             | looking for in anti-aging are "glasses for the body".
        
           | nhinck2 wrote:
           | Yes, immortality sounds horrible.
        
             | thriftwy wrote:
             | Do you want to die earlier rather than later, and/or in
             | worse health condition than possible?
             | 
             | That's what anti-aging is.
        
             | thr-nrg wrote:
             | [dead]
        
             | jack_pp wrote:
             | > Do you want to live forever, Harry?"
             | 
             | > "Yes, and so do you," said Harry. "I want to live one
             | more day. Tomorrow I will still want to live one more day.
             | Therefore I want to live forever, proof by induction on the
             | positive integers. If you don't want to die, it means you
             | want to live forever. If you don't want to live forever, it
             | means you want to die. You've got to do one or the other...
             | I'm not getting through here, am I."
             | 
             | It would be interesting to see how society will change when
             | we can make ourselves permanently healthy. Maybe people who
             | want to die will start taking extreme risks like sky-diving
             | or Russian roulette but the above quote stands imo. If you
             | don't want to live any more sounds to me like you have a
             | psychological problem. I don't mean that 80 year olds, that
             | have a dozen physical problems and struggle to do anything
             | and therefore want to die because life is unbearable, have
             | a psychological problem but if you're young, healthy and
             | still find no pleasure in living then maybe you should see
             | a therapist. Maybe the psychological part of living forever
             | needs to be solved too
        
               | BaculumMeumEst wrote:
               | that proof assumes the desire to live will remain
               | constant over time but it will not. parts of the human
               | body will decay and over time the will to live will drop.
               | 
               | death is inevitable. by artificially extending your
               | lifespan, you're not becoming immortal. you're taking an
               | event that typically comes as a natural part of life and
               | is out of your control and forcing yourself to choose
               | when it happens. you will have to choose at what point
               | your agony is so unbearable that you no longer want to
               | live.
               | 
               | people who are unlucky already have to live that hell in
               | modern times. i don't think people chasing this fever
               | dream have experienced the joy of seeing it play out.
        
               | Dylan16807 wrote:
               | If you can't picture yourself giving up an anti-aging
               | treatment without "unbearable agony" forcing your hand,
               | that's _your_ psychological hangup, not everyone else 's.
               | 
               | A normal person can just decide they're 200 and not
               | really enjoying much anymore and have that be the end of
               | it.
        
               | BaculumMeumEst wrote:
               | i'm arguing against the idea of achieving "immortality",
               | not against anti-aging treatments. slowing the
               | progression of aging but maintaining the same trajectory
               | of life and death is a desirable thing. trying to avoid
               | death is not.
        
               | jack_pp wrote:
               | Even then, maybe first see a therapist, try some
               | psychedelics or whatever. If you've tried everything and
               | somehow still see no point in living then yeah.. go
               | ahead.
               | 
               | I've been depressed a couple of times in my life and saw
               | no point in going further or living but I've talked
               | myself out of it by simply saying, hey, if I do this
               | relatively small thing and then do this thing that gives
               | me pleasure then that's better than literal death. I find
               | it hard to believe a person has experienced everything
               | there is to experience in 200 or even 1000 years. Our set
               | of experiences is what it is because of the short time
               | that we have but it doesn't mean it can't evolve to
               | accommodate a lifespan of 10x or 100x.
        
               | db48x wrote:
               | Your lifespan has already been artificially extended.
               | It's nearly twice the maximum of 10,000 years ago when
               | most people were nomadic, and about 20-25% longer than
               | that of the ancient Greeks, who retired from their
               | militia at 65 only if they made it that long.
               | 
               | And most of that life is spent in healthy youth and
               | middle age, not in continual decline. Today we expect to
               | become elderly in our 70s or 80s, and then die. The
               | Greeks became elderly in their 60s or even earlier. Is it
               | so hard to believe that in another 100 years people could
               | be living to their 90s or 100s before age catches up with
               | them?
        
               | BaculumMeumEst wrote:
               | i agree with everything you said. what i don't agree with
               | is that you can prove by induction that you want to live
               | for eternity.
        
               | jack_pp wrote:
               | > parts of the human body will decay and over time the
               | will to live will drop.
               | 
               | parts of the human body also evolve and strengthen over
               | time, unfortunately evolution also made them decay after
               | some point, that's what we're trying to fix.
               | 
               | > you're taking an event that typically comes as a
               | natural part of life and is out of your control..
               | 
               | this whole paragraph could apply to any physical problem.
               | You were born with XYZ health problem? just accept your
               | fate, it's natural. You got bit by a dog? Natural, just
               | accept your fate. You got an infection? why even bother
               | taking antibiotics, you're just forcing yourself to live
               | longer
        
               | ptsneves wrote:
               | The choice of death is a very good point. One would argue
               | that the difference between a natural death and a death
               | sentence is the knowledge and control of your life's
               | termination.
               | 
               | If people decide to end themselves that is suicide, and
               | if someone else decides it then that is murder. All these
               | are morally and ethically much more complicated than just
               | dying agentlessly.
        
               | carlmr wrote:
               | I personally think it would be so cool to see the world
               | evolve over thousands of years.
               | 
               | Maybe we'd be nicer to each other if we lived that long,
               | because we know our empire might be on top now, but
               | likely not through our lifetime.
               | 
               | But wealth inequality would probably be even worse,
               | because by the time one generation dies, they've already
               | bought up every piece of land in the world.
        
               | strken wrote:
               | "The water isn't boiling yet. In one minute the water
               | will still not have boiled. Therefore it will take
               | forever to bring this pot to boiling point, proof by
               | induction on the positive integers."
               | 
               | I broadly agree with lifespan and healthspan extension on
               | the grounds that one should get to choose the time and
               | manner of their passing, but that quote is just
               | ridiculous and Yudkowsky should have known better.
        
               | jack_pp wrote:
               | That quote is from the perspective of an 11-year old. I'd
               | say it fits the context and he wrote it well because even
               | though it's not an accurate and perfect view it is funny
        
             | bawolff wrote:
             | To be honest, i've always wondered how many people would
             | actually believe this if given the choice (assuming healthy
             | immortality). It always struck me a bit as the sort of
             | thing people say to be able to live with the fact they are
             | going to die and there is nothing they can do about it.
             | Always easier to accept something out of one's control by
             | pretending it is what you wanted all along.
        
             | vineyardmike wrote:
             | Immortality sounds horrible _if and only if_ I 'm the only
             | one immortal.
             | 
             | Most people don't want to die. I want to learn more, and
             | indulge curiosity for another day. I want to laugh and love
             | and see my family forever longer - I don't think I'd ever
             | wish to leave my loved ones, and I will unsurprisingly
             | mourn their loss. I assume I'm not particularly special in
             | any of this...
             | 
             | I think the sudden onset of immortality (especially
             | concentrated on the wealthy) will be catastrophic for
             | society. Imagine Bezos or a Kardashian or someone
             | politically motivated like Murdoch/Soros but _immortal_?
             | Imagine them being able to spend (and grow) generations of
             | wealth... for generation?
             | 
             | For the rest of us, the cost of an opportunity to be
             | immortal will be massive because of course it can be.
             | People today save for retirement, but one day they may save
             | for immortality - or perhaps take out insane loans to fund
             | it. Imagine real estate prices when banks can offer 100y
             | mortgages to a class of rich immortal workers? Imagine
             | trying to advance in your career when someone can get a
             | senior job and work for hundreds of years, especially if
             | they need to fund their 100y mortgage or their immortality
             | procedure - Millennials already complain that boomers won't
             | retire and open up the higher-rung jobs.
             | 
             | Immortality would upend society, and likely exacerbate
             | social tensions, but it could also be a great reset in
             | social expectations. Maybe it'd encourage _everyone_ to
             | take a long-term view of their actions. eg. Climate change
             | would impact everyone, so no one would be  "too old to
             | care".
        
         | [deleted]
        
         | zo1 wrote:
         | It's simple. We want trusted individuals and knowledgeable
         | debate on the topic, especially for one so controversial. And
         | yet, this entire thread is now revolving on your meta
         | commentary on the topic. Very disappointing.
         | 
         | It doesn't pop up nearly as us fans would like, and I barely
         | see it once a month on here.
        
         | pupppet wrote:
         | I mean, HN has more than a few Peter Thiel fans..
        
         | ycombinete wrote:
         | There are many avid sci-fi fans here. So it's likely as much to
         | do with piqued interest (scientific or philisophical), as it is
         | to do with not wanting to die.
         | 
         | Someone who loved reading _Time Enough for Love_ , or
         | _Permutation City_ , is probably going to be interested in the
         | subject.
        
         | thr-nrg wrote:
         | [dead]
        
       | 34679 wrote:
       | 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
        
         | stephenitis wrote:
         | I second this podcast, great vivid storytelling.
        
       | CapstanRoller wrote:
       | Rapamycin is also being studied as a booster drug to ketamine for
       | treatment-resistant depression
       | 
       | https://www.bbrfoundation.org/content/surprising-clinical-tr...
        
       | EdwardDiego wrote:
       | 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?
        
       | snvzz wrote:
       | Tangentially related: Fable of the Dragon-Tyrant[0].
       | 
       | 0. https://www.youtube.com/watch?v=cZYNADOHhVY
        
         | drBonkers wrote:
         | I didn't realize this short was first a textual story [1] until
         | years after my first encounter.
         | 
         | [1] https://nickbostrom.com/fable/dragon
        
           | snvzz wrote:
           | 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
           | 
           | 1. https://hsr.hoyoverse.com/
        
       ___________________________________________________________________
       (page generated 2023-05-08 23:01 UTC)