[HN Gopher] Metformin decelerates aging clock in male monkeys
___________________________________________________________________
Metformin decelerates aging clock in male monkeys
Author : tortilla
Score : 154 points
Date : 2024-09-12 16:56 UTC (6 hours ago)
(HTM) web link (www.cell.com)
(TXT) w3m dump (www.cell.com)
| ninetyninenine wrote:
| >https://www.frontiersin.org/journals/endocrinology/articles/...
|
| Data is controversial. It's not "not enough" data or anything
| like that either.
| MarkusQ wrote:
| 1) Not clear how lit review published in 2021 casts doubt on a
| study published in 2024
|
| 2) The lit review does not say the data is controversial, only
| that the claim of life extension is, and then goes on to say
| "However, via its ability to reduce early mortality associated
| with various diseases, including diabetes, cardiovascular
| disease, cognitive decline and cancer, metformin can improve
| healthspan thereby extending the period of life spent in good
| health" which is entirely consistent with the monkey study
| under discussion here
| adrian_b wrote:
| That article discusses the earlier experiments on nematodes and
| mice and doubts the applicability to humans of some results.
|
| This new study provides data about positive results in
| primates, so it removes some of the earlier objections.
|
| Nevertheless, it is not clear yet whether the risks of harmful
| effects of long-term treatment with high doses of metformin do
| not outweigh its beneficial effects.
|
| Where I agree with the article linked by you is that metformin
| is not the actual cause of lifespan extension, but it mimics
| the effects of some other primary cause, perhaps calorie
| restriction.
|
| Therefore, the studies on the metformin effects should
| concentrate on establishing which is the mechanism of its
| action, even if that is much more difficult than just
| establishing a correlation between metformin intake and ageing.
| When the mechanism of metformin action will be understood, it
| is likely that the same effects will be achievable in safer
| ways.
| bognition wrote:
| Interesting, Metformin is mostly commonly used to help treat high
| sugar levels in diabetics. I'm curious if this is the same
| mechanism or if its a novel mechanism.
|
| There's data to suggest that too much sugar can cause all kinds
| of problems to the brain, increasing oxidative stress is one of
| them.
|
| Maybe the answer we're all looking for is to cut sugar from our
| diets.
| PaulHoule wrote:
| The "sugar" in "high blood sugar" is glucose. Your body
| converts starches (say rice or bread) into glucose quite
| quickly which elevates your "blood sugar" in the short term. If
| you are healthy your body can quickly turn glucose into
| glycogen or fats or utilize it as an energy source but if you
| have Type I or Type II diabetes that process is impaired.
|
| If you cut back radically on carbohydrate consumption, see
|
| https://en.wikipedia.org/wiki/Ketogenic_diet
|
| you certainly will lower your blood sugar, your body will now
| use proteins and fat for energy as much as it can and produce
| both ketone bodies and glucose from those other macronutrients
| as well as stored fat and muscle tissues.
|
| Table sugar and 'high fructose corn syrup' are roughly
| equivalent to 50% fructose and 50% glucose so far as your
| metabolism are concerned. Certainly fruit (rich in fructose and
| sometimes sugar alcohols) is good for you in moderation but
| probably not in excess. Your metabolism is certainly capable of
| converting fructose and some sugar alcohols into glucose. The
| story of what fructose does to you is much less studied than
| glucose. Certainly excessive amounts of sucrose and HFCS
| contribute empty calories that raise your blood sugar.
| catlikesshrimp wrote:
| You can safely remove the quotes around 'glucose' and replace
| "high blood sugar" with 'glycemia'
| fnord77 wrote:
| metformin can also cause gastroparesis, which is a nasty
| condition I wouldn't wish on anyone.
| toomuchtodo wrote:
| Something to be aware of is that it can cause genital physical
| deformities in male offspring.
|
| > Boys were more likely to be born with genital birth defects
| if their fathers took the commonly prescribed diabetes drug
| metformin in the three months before conception, according to a
| new study by Stanford Medicine investigators and their
| collaborators in Denmark.
|
| https://med.stanford.edu/news/all-news/2022/03/birth-defects...
|
| https://www.acpjournals.org/doi/10.7326/M21-4389
| antisthenes wrote:
| It's a good idea to go on a "purge" before attempting
| conception, for both males and females, lasting at least 5-6
| months
|
| E.g. cut out bad foods, any drugs, exercise regularly.
| caseyy wrote:
| It does often cause significant gastrointestinal problems. Same
| as weight loss drugs. A lot of people think these drugs are
| free lunch but they are not.
| epasveer wrote:
| My experience with metformin, those gastrointestinal problems
| occur the first 4 months of taking it.
|
| I had an experience in a Home Depot, had to briskly walk to
| the bathroom. Like clenching a quater between your cheeks for
| a 100 yards. Barely made it.
|
| Anyway, the body adjusts. After 3 or 4 months, all is good.
| caseyy wrote:
| Hmm, that is a very long time to suffer the side effects.
| The information leaflets often say to discontinue much
| sooner.
|
| Well, if your doctor was okay with it, then who are
| internet strangers to judge? If you had the usual non-
| tolerance GI problems (more frequent than in 1 in 10
| patients), I can only admire the perseverance. It takes a
| lot of self-care from keeping close to a toilet to
| hydration.
| generalizations wrote:
| https://en.wikipedia.org/wiki/Metformin:
|
| > It works by decreasing glucose production in the liver,
| increasing the insulin sensitivity of body tissues, and
| increasing GDF15 secretion, which _reduces appetite and caloric
| intake._
|
| Emphasis mine. So, looks like the actual aging deceleration is
| just the cliche, that it's healthy to not be overweight?
| arcticbull wrote:
| Likely not.
|
| A principal mechanism of action of metformin is AMPK-
| dependenent inhibition of mTORC1 in the liver. [1] mTORC1
| inhibition also occurs when fasted and when taking Rapamycin.
| Rapamycin has been floated many times as a life extension drug.
| [2]
|
| mTOR is one of the major nutrient sensing pathways in the body,
| particularly sensitive to amino acids (especially methionine
| and leucine) but also to energy levels in general via AMPK.
| Inhibition of mTOR slows down cell division and induces
| autophagic flux -- further mTOR dysregulation is implicated in
| about 70% of cancers. It is an incredibly highly conserved
| pathway in everything from yeast to humans, and [m]TOR
| inhibition has been shown to dramatically extend life in
| basically everything that moves. I believe there's a life
| extension trial in humans under way around Rapamycin but I
| could be mistaken.
|
| It acts as a very targeted partial starvation mimetic.
|
| [edit] > that it's healthy to not be overweight?
|
| This is separately also true. But what's neat about metformin
| is that generally diabetics on metformin are less likely to
| develop cancer than _non-diabetics_. [3] So it stands to reason
| that non-diabetics taking metformin would have even lower
| incidence of cancer no?
|
| [edit] I find this stuff very cool, and I personally expect
| mTOR to be the next golden child after everyone gets on GLP-1s.
|
| [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299044/
|
| [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/
|
| [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841986/
| riehwvfbk wrote:
| Everyone on GLP-1s? Is that a future most people actually
| want?
|
| I believe that these things work. But I for one don't want
| more years as a wage slave, particularly when coupled with
| anhedonia. Sure, I'll extract more value for my corporate
| overlords, but what's in it for me? For some definition a
| long life without any pleasure is an optimization, but I'd
| argue the validity of this definition.
| arcticbull wrote:
| > Everyone on GLP-1s? Is that a future most people actually
| want?
|
| I want a future where people aren't dying of cancer,
| cardiovascular disease, losing limbs and eyes to diabetes,
| getting strokes and where they're living long and healthy
| lives. I don't really care so much about the means. GLP-1s
| are the only proven non-surgical intervention that allows
| people to lose a clinically significant (>5%) amount of
| weight and keep it off long-term (>5 years).
| riehwvfbk wrote:
| So instead of natural selection making it so that people
| who live longer aren't affected by these issues - you'll
| have a populace that is dependent on a drug. Perfect
| recipe for powerful centralized control I suppose.
| mahin wrote:
| So just like all the life saving drugs being prescribed
| now?
| daedrdev wrote:
| We have destroyed natural selection in humans a long time
| ago when by creating effective healthcare, so don't worry
| about it.
|
| There are many companies making different versions of
| this drug, I don't see why you think its some kind of
| conspiracy intended to control the masses, literally if
| the benefit is greater than the costs what is your issue
| with it?
| daedrdev wrote:
| > Everyone on GLP-1s? Is that a future most people actually
| want?
|
| If it's a net positive to my life what is the problem?
|
| You have a very dismal view of the world, it is possible to
| enjoy one's work, or at least tolerate it, or work for
| yourself in the current economic system. Personally I
| appreciate the improved standard of living I have thanks to
| the efficiency of our profit driven system.
| cleandreams wrote:
| I'm retired and on metformin. I feel great. The wage slave
| problem is a separate problem for which there is only a
| political, not medical, solution.
| boringg wrote:
| What has Met done for you? Curious what noticeable
| impacts you feel/see.
| singlow wrote:
| I can't say what MetFORMin did for me on its own since I
| also changed my diet and lifestyle significantly when I
| started it. But since starting it I lost 50 pounds, and
| got my blood sugar from a diabetic range into a normal
| range, along with many positive side effects such as
| increased energy, no more sleep apnea, blood pressure in
| normal range (was over 170/90). Again MET didn't do these
| things itself, but I do think it helped to achieve the
| weight loss and blood sugar control that would have been
| harder without it. I was on a low dose and never had any
| negative side effects, and am now off of it after 6
| months and maintaining.
| cleandreams wrote:
| I describe it as "appetite calming." Not sure how else to
| put it. I used to have a low grade constant craving for
| food. I wasn't obese but the weight had crept up. Losing
| weight was impossible. I had high blood sugar, blood
| pressure, and cholesterol. (Now on meds for all those
| things and they are under control.)
|
| Immediately after going on metformin my appetite calmed.
| Slowly, over the next year, I lost 25 pounds. I did not
| try to diet. My BMI is now 23.7.
|
| After a few months I started weight training. I changed
| my diet to lower carbs. I haven't lowered my HbA1c into a
| totally comfortable level (it is 5.6 and 5.7 and above is
| prediabetic). But I am better.
|
| But before any of those changes, just the Metformin alone
| calmed my appetite. I can go hours without thinking about
| food. I am just less concerned. I feel normal.
|
| Just as a data point, the last time I got Covid, it was
| quite mild. It's at least possible that the better
| metabolic health and weight loss had an impact.
| robwwilliams wrote:
| Absolutely not unless you are fighting serious obesity. In
| contrast, I can imagine low dose intermittent mTORC1
| inhibition as generally advantageous over a much wider
| population of individuals 50 years and older.
| sctb wrote:
| Do you have a sense of how different mTOR-related
| interventions stack up? As in, metformin vs rapamycin vs
| intermittent fasting?
| robwwilliams wrote:
| Rapamycin and related rapalogs will be far better than
| metformin at inhibiting mTORC1, and at a low and
| intermittent dose of 4-6 mg ONCE per week are quite safe.
| Best paper I know of now is Kaeberlein et al 2023:
|
| https://pubmed.ncbi.nlm.nih.gov/37191826/
| fellowniusmonk wrote:
| What about stuff like Berberine? Is that all smoke and
| mirror? It's always hard to tell if the research around
| "traditional" compounds is actually legit or just other
| countries engaging in what is effectively marketing.
| robwwilliams wrote:
| I agree with your enthusiasm for treatments and drugs that
| inhibit mTORC1 selectively. Low dose rapamycin is our best
| practical pro-longevity treatment today. I only wish we had a
| large randomized clinical trial for stronger direct support.
|
| In contrast, the evidence of any direct in vivo action of
| metformin on mTORC1 is dubious. In vitro studies may be of
| little relevance in this context.
|
| Even indirect effects of metformin via AMPK activation are
| controversial.
|
| A careful study by Keys and colleagues of a large Danish
| cohort of twins (2022)found no reduction in all-cause
| mortality by metformin treatment.
|
| They point out that the highly influential Bannister et al.
| study (2014, pushed by a high profile TED presentation) has
| not been replicated despite a 10-year period in which to do
| so. Here is the link to the Keys paper that makes me highly
| skeptical about use of metformin to modulate aging rates.
|
| https://pubmed.ncbi.nlm.nih.gov/36287641/
|
| Could you highlight any strong in vivo studies on metformin
| targeting mTORC1 selectively or otherwise?
|
| I am not quite sure what to make of this Cell paper yet.
|
| In the NIA Interventions Testing Program (systematic studies
| of the impact of drugs on longevity) metformin has inly weak
| effects in males (p ~0.3) and no effect in females:
|
| https://phenome.jax.org/itp/surv/Met/C2012
|
| In contrast adding rapamycin work wonders (in mice).
| onlyrealcuzzo wrote:
| > Emphasis mine. So, looks like the actual aging deceleration
| is just the cliche, that it's healthy to not be overweight?
|
| Are typical monkeys obese like typical Americans?
| bee_rider wrote:
| I wonder how they control for that in lab monkeys. They
| aren't typical, right? I guess they probably get less
| exercise than wild monkeys.
| ugh123 wrote:
| This article describes some of what they do with lab
| primates for obesity:
| https://www.nytimes.com/2011/02/20/health/20monkey.html
|
| Essentially: put them in small cages for years, give them a
| nearly unlimited supply of food, and give them nothing to
| do. Terrible.
| dukeofdoom wrote:
| This guy gives a pretty good explanation of (Insulin's effects
| on the body), from the point of view of adapting it into a
| lifestyle diet. He also built a pretty amazing DIY cottage in
| Costa Rica. https://www.youtube.com/watch?v=hDxXprgv3kk&t=2s
|
| This video actually helped to motivate me to get into meal
| prepping, and significant weight loss.
| bityard wrote:
| Despite the unnecessarily picturesque location and overt
| shirtlessness, this was actually an accurate overview of
| nutritional metabolism for how short it is.
|
| I've been researching this topic (in the context of keto) on
| my own for the last 10 years or so and can say that nothing
| he said is wrong. I don't know why all of this isn't common
| knowledge at this point, other than the signal just gets lost
| in the noise between dry research papers and fad-pushing
| articles and products.
| hinkley wrote:
| It usually gets attributed to oxidative stress, but I think
| it's also more exposure to toxins and inflammation sources.
|
| Your mercury load is higher if you eat twice as much fish,
| meanwhile the benefits of eating some fish are proportionally
| higher than eating a lot of fish. You want small portions of a
| lot of things, not large portions nor narrow selection.
| arcticbull wrote:
| From the lens of the mTOR model -- if you just eat a lot of
| food all the time, mTOR is constantly agonized and your body
| consistently operates in anabolic mode. Periods of fasting
| (either explicit through hours/days without eating, or
| implicit through low calorie diets, or synthetic via
| metformin or rapamycin) allow your body to enter catabolic
| mode and tear down aggregated and misfolded proteins. Recent
| Noble Prize winner Yoshinori Otsumi discovered autophagy does
| that specifically. [1, 2]
|
| As a SWE/EE I tend to look at things through that lens, and
| it seems like most processes in the body are AC coupled. DC
| signals tend to get filtered out and not recognized properly.
| Lower calorie diets and fasting convert mTOR agonism from a
| DC signal to an AC signal and it's the periodic alternation
| of modes that keeps you healthy. Periods where you can tear
| down the broken and periods where you can rebuild.
|
| Another example, people look at stress hormone cortisol as
| leading to central adiposity in the context of insulin
| resistance. This is fundamentally backwards - cortisol is a
| potent insulin _antagonist_ , it's a catabolic hormone that
| prevents insulin secretion, disrupts insulin signaling and
| mobilizes stored fat. The problem is when it's _constantly_
| elevated (DC signal) it stops working, and the opposite
| happens.
|
| mTOR inhibition also modulates the immune system and
| suppresses hyperimmunity. This reduces inflammation (via
| Hypoxia-indidible factor 1-alpha / HIF1A and several
| downstream processes). Which explains why metformin reduces
| inflammation too. Even more interesting is that inhibition of
| mTOR in the AMPK-mTOR-HIF1A pathway makes vaccines
| significantly less effective.
|
| [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329718/
|
| [2] https://www.nobelprize.org/prizes/medicine/2016/press-
| releas...
| hinkley wrote:
| I walk first thing in the morning before eating. So that's
| fasting exercise. It's definitely pulled down my pain
| levels enough that I'm putting off medical intervention for
| now. I do need to go in anyway because I want to see where
| my A1Cs are. I was flirting with the lower edge of the
| danger zone a few years ago.
| datavirtue wrote:
| 1:1 gummies. THC + CBD, CBG Overlap them, 5mg, wait two
| hours, 5mg... three or four times
|
| Maybe try 10mg doses but the 5g should do it.
|
| Inflammation bitch slap.
| devmor wrote:
| How does this reconcile with recent studies that
| intermittent fasting is severely detrimental to lifespan?
| (https://newsroom.heart.org/news/8-hour-time-restricted-
| eatin...)
|
| Is it two antagonistic factors that require us to meet in
| the middle to find the healthiest balance or is there
| something else at play?
| arcticbull wrote:
| I absolutely hate nutritional studies.
|
| My first quibble is: honestly an 8 hour window for eating
| is pretty large, that's like, late breakfast, lunch and
| dinner. Is that fasting? It seems like kind of a normal
| eating schedule.
|
| My first thought when I read something like this is "why
| would it be severely detrimental" and the first response
| is "the kind of people who are overweight are the ones
| who are going to be trying new diets to lose weight, and
| being overweight in the first place is severely
| detrimental to lifespan." Controlling for that, there may
| be something further confounding, for instance.
|
| People skip breakfast all the time, and skipping
| breakfast leads to a 60% increase cancer risk. Peter
| Attia has a writeup on this [1]. Turns out, the people
| who skip breakfast are far less health conscious. People
| who skipped breakfast were 3X as likely to smoke. As he
| says, 'health and lifestyle characteristics between
| groups can either mask or exaggerate the association
| between frequency of breakfast consumption and
| mortality.'
|
| I'd be very surprised if a kinda normal ish eating
| schedule led to a materially worse outcome when properly
| controlled. But proper control is damn near impossible in
| nutrition studies.
|
| [1] https://peterattiamd.com/does-skipping-breakfast-
| increase-th...
| StanislavPetrov wrote:
| >My first quibble is: honestly an 8 hour window for
| eating is pretty large, that's like, late breakfast,
| lunch and dinner. Is that fasting? It seems like kind of
| a normal eating schedule.
|
| Even worse, they define, "time-restricted eating" as
| being up to 12 hours!
|
| >Time-restricted eating, a type of intermittent fasting,
| involves limiting the hours for eating to a specific
| number of hours each day, which may range from a 4- to
| 12-hour time window in 24 hours.
| hooverd wrote:
| Fasting increases nitric oxide levels. Maybe that's bad
| for people with existing cardiovascular issues? Probably
| the same people who would try intermittent fasting- it's
| a relatively bigger population. Of course you have to
| balance that against complications from being overweight.
| arcticbull wrote:
| Nitric oxide actually dilates your blood vessels, reduces
| blood pressure and improves cardiovascular outcomes. [1]
| Water fasting for a couple of days brings your systolic
| and diastolic numbers waaaaay down over 10 days.
|
| > The average reduction in blood pressure was 37/13 mm
| Hg, with the greatest decrease being observed for
| subjects with the most severe hypertension. [2]
|
| It's probably just a poor job of controlling variables in
| the study.
|
| [1] https://pubmed.ncbi.nlm.nih.gov/15722114/
|
| [2] https://pubmed.ncbi.nlm.nih.gov/11416824/
| robwwilliams wrote:
| That study is an abstract and was not peer reviewed. I
| find this an implausible result. Is there a version that
| has been peer reviewed yet?
| dewarrn1 wrote:
| Interesting work. There are also clinical trials, recent and
| ongoing, looking at the effects of metformin on aging in humans,
| too, including the TAME trial[0].
|
| [0]: https://www.afar.org/tame-trial
| matthewdgreen wrote:
| For those who can't access the article, the dosage they used
| was 20mg/kg per day. The pills I've seen are 500mg, so for me
| that works out to 3-4 pills per day. I know some people who
| already take doses like that for high blood sugar with no ill
| effects, but some also do have ill effects. Also I am not a
| monkey, so no idea if this would be a great idea to try.
|
| I couldn't find the exact doses TAME is using, but some
| writeups point out that there's no effect on glucose levels
| beyond about 1,600mg per day.
| thehappypm wrote:
| > Also I am not a monkey
|
| [Citation Needed]
| leptons wrote:
| I've been taking 2000mg of metformin every day for years, no
| ill effects. I guess I'm one of the lucky ones? Also, I'm a
| type of monkey more commonly referred to as "human".
| falcolas wrote:
| 1k pills here, but I can only take one once a day. They're
| really hard on the stomach, and even when taken with food. A
| second pill (which my doctor would like to see) just always
| makes me puke.
| robwwilliams wrote:
| TAME has not yet been funded by NIA. Stay tuned.
| aanet wrote:
| Here's more info [1] on the TAM trial, courtesy of Dr Michael
| Greger.
|
| Apparently, the TAME trial has gotten FDA approval since 2015,
| but has yet to be launched as a full fledged clinical trial,
| apparently because _" there is no way in hell to make money on
| it. So how would we fund a clinical trial? Well, yes, the only
| way is philanthropic"_ [2]
|
| [1] https://nutritionfacts.org/video/the-tame-trial-targeting-
| ag... [2] https://youtu.be/_9I0R8I16XQ?feature=shared&t=105
| testfrequency wrote:
| Not going to lie, I really hate all the recent coverage on
| Metformin becoming a "miracle pill" - as I've been on Metformin
| for almost 10 years now without issue.
|
| I really hope my prescription costs and access to Metformin is
| not ruined by everyone's quest to out live their children
| 7e wrote:
| Metformin is off patent and is easy to make. You will have no
| problems.
| fzingle wrote:
| So is insulin. But at least in the US, it is expensive.
| adrianN wrote:
| It is my understanding that the expensive insulin is
| actually more complicated than the insulin that we had a
| couple of decades ago and that makes it easier to dose
| correctly so that therapeutic outcomes are improved.
| munk-a wrote:
| That was due to cartel behavior (and now should be limited
| by the recent drug capping initiative) - elsewhere in the
| world insulin is extremely affordable.
|
| Insulin is an interesting case because the insulin you get
| today is manufactured in a different process than the
| original batches which has let manufacturers skirt around
| both generic alternatives and the original patent.
| kurthr wrote:
| Well, not so much anymore. It's capped at $35/mo if you're
| on Medicare or ACA and most other sources.
|
| https://investor.lilly.com/news-releases/news-release-
| detail...
|
| I'd also mention that most of the insulin these days is not
| extracted from animals as it once was. One can make
| arguments for/against this, but for safety reasons almost
| all of it is now made with biopharmaceutical (bacterial
| recombinant) processes.
| epasveer wrote:
| I believe it's expensive for the delivery system, not the
| insulin itself. (Could be wrong).
| klooney wrote:
| Off patent it's cheap, but the on patent stuff is way
| better, so it's what everyone wants
| zamadatix wrote:
| I'm on Metformin and not worried about it given the likely
| reason you ended up on Metformin 10 years ago is it was already
| generic and cheap to make, especially compared to many of the
| alternatives. Where you get screwed is needing a pill that's
| under heavy patents or still complicated/expensive to make even
| when it isn't.
| renewiltord wrote:
| Artificial scarcity of these drugs is an intentional choice.
| __MatrixMan__ wrote:
| We need more garage chemists so that it can be a less
| consequential one.
| renewiltord wrote:
| Compounding pharmacies get around this. My friend runs a
| very profitable online pharmacy backed by them (which he
| also owns).
| DeonPenny wrote:
| More people taking medication lower price not increases it.
| bityard wrote:
| That is true in a lot of areas. Unfortunately, that's not how
| the pharma industry works. If a medication is patented, the
| company who owns it sets the price (or licensing price)
| according to demand. As an example, there was a scandal or
| two in the past few years where private equity firms were
| buying pharma companies and jacking up the price of
| medications to the point where the users of those medications
| got to choose between bankruptcy and living.
|
| (Disclaimer 1: I don't know if metformin is patented.)
|
| (Disclaimer 2: This is not an anti-capitlaist rant.
| Capitalism works fine with adequate governmental regulation.
| However, practically nothing about the US healthcare system
| is adequately regulated.)
| birriel wrote:
| It's so frustrating to get seemingly contradictory results across
| species with the same treatment. The Interventions Testing
| Program found no increase in median or maximum lifespan in mice,
| male or female, treated with metformin (though it did in
| combination with rapamycin) [0].
|
| I realize "decelarating the aging clock" might be subtly
| different than increasing lifespan, but it's a reasonable enough
| comparison, imho. Hopefully we can soon capitalize on
| improvements in AI to faithfully model human biology in silico,
| and conduct experiments that way.
|
| [0] https://www.nia.nih.gov/research/dab/interventions-
| testing-p...
| tines wrote:
| Mice vs monkeys?
| trhway wrote:
| yep, mice are burning calories much more actively than larger
| mammals, and if anything i'd not be surprised for the
| opposite result - ie. if mice on metformin die earlier from
| exhaustion and starvation.
| hinkley wrote:
| Perhaps we should be looking at function levels at 70, 80, 90%
| of lifespan rather than looking for quantity of life.
|
| Logistically speaking, humans tend to have a lot of disposable
| income at 60-70% of life expectancy. From the Enlightened Self
| Interest perspective, extending that zone before functional
| decline would not only improve society but also be profitable.
| robwwilliams wrote:
| Yep, optimize healthspan not necessary lifespan. Best to do
| both and "rectangularize" survival functions (falling off a
| cliff). Lots of effort on this now.
| robwwilliams wrote:
| I am pessimistic about purely in silico or even in vitro
| methodd to tackle a problem as complex as aging rates.
| Improving mouse models to incorporate a high level of genetic
| diversity is a better first step. This is what our group of
| resesrchers is doing now. Results are promising and results are
| also highly dependent in genetics and sex.
|
| https://pubmed.ncbi.nlm.nih.gov/36173858/
|
| https://pubmed.ncbi.nlm.nih.gov/34666007/
|
| https://pubmed.ncbi.nlm.nih.gov/34552269/
| tocs3 wrote:
| If I am diagnosed with type II diabetes is it worth choosing
| metformin over other options (other considerations being the same
| for the different choices)?
| lambdaba wrote:
| What are the other options?
| tocs3 wrote:
| https://diabetes.org/health-wellness/medication/oral-
| other-i...
| bityard wrote:
| If you are open to controlling Type II diabetes by changing
| your diet, look up anything by Dr. Eric Westman.
| UncleSlacky wrote:
| Also look into the Newcastle Protocol and Prof. Roy Taylor:
|
| https://www.ncl.ac.uk/magres/research/diabetes/reversal/#pub.
| ..
| shaftway wrote:
| Metformin is almost always the first medication that you
| primary physician will prescribe, along with dietary
| restrictions. There's a reason it's first on almost every
| single list of diabetes medications. The side-effects are super
| low and rare, and maximum dosage of it is rather high.
|
| Three months later they check your A1C, and if you aren't
| responding to Metformin well enough then they'll slap on a
| second medication from one of the other categories. I think
| Sulfonylureas combine pretty well with it.
|
| If you're still not responding well your primary will give up
| and send you to an endocrinologist, who should have enough
| knowledge of the alternatives to discuss which one is best for
| you. It's completely fair to say "I'd like to try XYZ because
| the side effect of <side effect> appeals to me".
| catlikesshrimp wrote:
| Sulphonyl Ureas are known as secretagoges (They make the
| pancreas release more insulin) This has many metabolic
| drawbacks I won't go into.
|
| They reason they are prescribed everytime for DM II by
| insurance plans is that they are the cheapest drug for
| diabetes in the world.
|
| They are associated with either no improved mortality or
| worse mortality.
|
| They naturally don't work in DM I
| mint2 wrote:
| In addition to following your doctor's directions, It can't
| hurt to also check your diet is including enough vitamins and
| minerals - magnesium for example is a common deficiency and
| effects insulin. Although also make sure you doctor is aware of
| the supplements !
| datavirtue wrote:
| House said you should always lie.
| _qua wrote:
| Guidelines call for metformin first for most people, add ons
| from there are usually chosen based on the individual patient's
| comorbidities.
| logifail wrote:
| (Genuine Q): Why are people - or even just HN readers - really so
| interested in living longer?
|
| Both my father and my father-in-law have dementia.
|
| My father's dementia is fairly advanced (he doesn't know who I am
| and hasn't for a while, there are times where he doesn't know who
| my mother is) although he's still living at home.
|
| My father-in-law's dementia is less advanced although he's much
| more frail as he was diagnosed with bladder cancer, had it
| removed, so has ended up with the whole tubes+bags "solution".
|
| My OH and I were discussing this for the Nth time last week.
|
| Apologies for being blunt, but our current perspective is this:
| try make your life count, and hope for it to end cleanly. Via
| Dignitas, if necessary.
|
| There is no way I want to see out my final years in the way that
| my father or my father-in-law are doing now :(
| barrucadu wrote:
| Obviously the idea is to live longer with good mental and
| physical health.
|
| There's no point in living longer if your faculties are too
| degraded to enjoy it, you may as well just be dead.
| Jach wrote:
| I guess it's not so obvious if GP is the top comment. It
| seems broader messaging around anti-aging needs to be even
| better (nothing against the paper). Sometimes I like the
| jargon of negligible senescence and longevity escape
| velocity, because I don't think it's possible to know the
| meaning of those phrases and also think the goal is eking out
| as much substandard life as possible, so if you can't have a
| two-way conversation at least you can put in a semantic
| roadblock that invites a curious reader to look up the
| meaning and then not have the GP's question.
| ceejayoz wrote:
| I mean, we want to live longer _and_ not get dementia.
|
| I wanna know what happens. I want to download my brain into a
| computer and see what humanity does over the next couple
| million years.
| highwaylights wrote:
| Even if that were possible, and theoretically we could take
| the entirety of a person's brain and emulate every synapse
| into digital storage, along with enough compute to run
| everything (which is a massive hurdle to overcome), would it
| really still be _you_?
|
| I kind of think about it a bit like the transporter deck from
| Star Trek. Are those people really travelling somewhere else
| or are they getting cloned and then done like Hugh Jackman at
| the end of The Prestige?
|
| How would anyone even know? A computer simulated you would
| _seem_ like you to everyone else, but you 'd already be gone.
| incongruity wrote:
| Worse, still, unless the current me blinks out of
| existence, "old me" will still be around - unless we can
| replace neurons in-place with computational analogs, the
| original me is destined to die, almost no matter what, even
| if a copy/download is made. From the download's
| perspective, it continues, but the original, if not ended
| then and there, still faces a grim end and will know it.
| ceejayoz wrote:
| If painless (or I don't remember it), I'm 100% fine with
| a fairly speedy destructive upload process.
| highwaylights wrote:
| You won't remember it as you'll cease to exist at all is
| the point.
| ceejayoz wrote:
| My consciousness gets interrupted on a nightly basis. One
| more will be fine.
| ceejayoz wrote:
| > How would anyone even know?
|
| If no one can ever know, I'm not sure I care. Transport me
| to cool places all you like.
| nikkwong wrote:
| The correct answer is that there is no "you". Continuity in
| consciousness is an illusion that can be deconstructed
| through deep enough meditation, or more accessibly through
| psychedelics. It certainly feels like there is as "you" at
| the center, but what you call "you" is sort of a narrative
| that your brain is stitching together at each moment, and
| it can be subject to distortion, revision, reinvention.
|
| You are not the same "you" from moment to moment--you are
| just reassembled by your brain every second in a way that
| feels conscious. So I would say there is a false dichotomy
| in the center here. If "you" are already an illusion,
| digital emulation just manipulates that illusion in
| different ways. Whether or not "you" survive in a literal
| sense is not the right question, there was not a fixed
| "you" to keep or lose in the first place
| cbsks wrote:
| I'm in the middle of a sci-fi book that explores this. The
| answer is that you won't be the same person. Your mind will
| meld with the computer's AI and you will go insane and try
| to exterminate the human race. I wouldn't risk it.
| logifail wrote:
| > we want to live longer and not get dementia
|
| ...but why? Dying is natural. Dying is normal. It's what's
| supposed to happen.
|
| > I wanna know what happens
|
| I've reproduced three times so I've ticked that particular
| biological box.
|
| My OH is away this week. Our eldest cooked lunch on Tuesday
| when a meeting I was in ran over by an hour. I stumbled into
| the kitchen an hour later than planned to find the three of
| them eating what he'd prepared from what he'd found in the
| fridge and he'd made enough for me, too. They're pretty well
| set.
|
| > I want to download my brain into a computer and see what
| humanity does over the next couple million years
|
| I'm absolutely, completely OK with not doing that :)
|
| I'm confident the next generation will figure it out, just
| like ours did, and the one before us, and so on...
| lucb1e wrote:
| It's also natural and normal to die in infancy, but we've
| solved that and I don't hear many complaints
|
| Edit: looked it up, 49% is the estimated rate for hunter-
| gatherer societies and 48% until ~200 years ago (depending
| on the country, may also be ~60% or as "low" as ~40%). In
| 1950 it was still more than a quarter; only within living
| memory has it truly become abnormal to die soon after
| birth. https://ourworldindata.org/child-mortality
|
| This argument of what's "natural" holds so little water to
| me, I don't understand in what state of belief anyone even
| brings this up. Is this a religious thing? Why say "it's
| natural to die and therefore we should always continue to
| do so"? Arguments of overpopulation, psychological issues
| (and unknown unknowns), and other real problems, I can
| certainly understand, but "it's natural"? Please explain
| ceejayoz wrote:
| > It's what's supposed to happen.
|
| I wear glasses, clothes, and my kids were born three months
| early. I, and they, were supposed to die.
| tempestn wrote:
| As others said, obviously the goal is to live longer in good
| health. As for why, because.. I like living. Why would I not
| want to do it for longer?
| dangus wrote:
| People want more healthy years.
| logifail wrote:
| > People want more healthy years
|
| ...but that doesn't really answer _why_ , does it? To "do
| more stuff"? To "see more things"? To "earn more money"? To
| "learn more"? Why?
|
| A friend wasn't enjoying her job a year or two ago and said
| she felt seriously underpaid for the stuff she was being
| asked to handle. I asked her if she would feel any happier if
| they doubled or tripled her salary. After thinking about it
| she realised the amount of money wouldn't fix the problem,
| the issue was with the work environment, not the monetary
| package tagged on to her employment.
|
| Life is finite.
|
| So at least for all of us who don't have some desperately
| unkind medical issue that specifically shortens it, maybe we
| need to take a deep breath and learn to deal with that.
|
| "Carpe diem", and all that.
| jjk166 wrote:
| > To "do more stuff"? To "see more things"? To "earn more
| money"? To "learn more"? Why?
|
| Yes, to all of it.
|
| Life will still be finite with a longer life, but more is
| more. If offered the opportunity to have your lifespan
| shortened for no gain would you take it? Obviously not, and
| likewise if you have the opportunity to increase your
| lifespan for no cost, it's exactly the same decision.
| rileymat2 wrote:
| I am not sure if it would map to dementia, but:
|
| > The results highlighted a significant slowing of aging
| indicators, notably a roughly 6-year regression in brain aging.
|
| And some people call Alzheimer's type 3 diabetes. So there
| could be something protective?
| transitionnel wrote:
| Diabetes causes rupturing of small blood vessels, which has
| been seen in eyes and feet. It would follow that the same is
| happening in the brain and an anti-diabetic medicine would
| directly improve brain longevity in affected individuals.
|
| *I am not a doctor, but also I can correlate data without
| bias.
| non- wrote:
| The exciting thing about these findings is not that the
| monkey's live longer, it's that their brains aged slower.
|
| ---
|
| Highlights:
|
| * Metformin prevents brain atrophy, elevating cognitive
| function in aged male primates
|
| * Metformin slows the pace of aging across diverse male primate
| tissues
|
| * Metformin counterparts neuronal aging, delivering
| geroprotection via Nrf2 in male primates
| iwontberude wrote:
| * Metformin-associated lactic acidosis has an estimated death
| rate of up to 50%.
| switchbak wrote:
| The people in this space talk a lot about not just life span,
| but health span. I don't know anyone who wants to suffer for a
| long time, of course we'd want to live well.
|
| I know for myself, I'd love to be around to watch my kids grow
| up. Even better if I can do that while being old-man jacked and
| physically capable enough to still enjoy life. I don't think
| this has to mean that you're putting off enjoying life in the
| current moment though.
|
| It seems like a funny question to ask who's "interested in
| living longer"? Taken to an extreme that's a pretty depression
| question.
| a13n wrote:
| Survival instinct is deeply hard wired into all animals,
| including humans. It's natural to want to continue living.
|
| Anti-aging is picking up now because there's a growing belief
| that significantly extending the healthy human lifespan is
| within scientific/technological reach.
| logifail wrote:
| > Survival instinct is deeply hard wired into all animals,
| including humans.
|
| Survive _and reproduce_...
|
| So if/when one has the reproduction bit out that of the
| way, the survival bit _as such_ may not seem to be quite as
| vital.
|
| You know your genes are going to survive, meaning _you don
| 't personally have to_. Which is the whole point of
| evolution, right?
| inglor_cz wrote:
| "Which is the whole point of evolution, right?"
|
| Pretty much the entire point of civilization is _not to
| be at the mercy of natural forces_ , including evolution.
| logifail wrote:
| > Pretty much the entire point of civilization is not to
| be at the mercy of natural forces, including evolution
|
| The parent to my comment did bring up "survival
| _instinct_ " (!)
| inglor_cz wrote:
| Sex, hunger, sleep are all instincts, but civilization
| tries to make their satisfaction nicer, safer, cheaper,
| more reliable.
| a13n wrote:
| I don't know that we have evidence that survival instinct
| goes away after reproduction. It's still valuable to our
| species to survive after reproduction in order to protect
| and nurture offspring, for example.
|
| There's no evolutionary reason that survival instinct
| would turn off after a certain age.
| logifail wrote:
| > There's no evolutionary reason that survival instinct
| would turn off after a certain age
|
| Umm, without wishing to get too clinical or morbid, it's
| clear that once your offspring have reached adulthood
| there will always come a point beyond which you rely on
| them more than they rely on you, right?
| stickfigure wrote:
| Evolution is not a motivational poster or a speech from
| your therapist. It's just the outcome of a physical and
| biological process. It just is.
|
| I personally would prefer to survive longer. If you
| don't, that's your business.
| logifail wrote:
| > I personally would prefer to survive longer. If you
| don't, that's your business.
|
| Ideally I'd die in my sleep 75-80 +/- a few years having
| seen some grandkids. Doing daft stuff now to push that
| number further out just seems pointless.
|
| The next generations will have enough problems to deal
| with without having one more cranky 90+ year-old
| constantly popping pills claiming he can live forever.
| shermantanktop wrote:
| And voting.
| onemoresoop wrote:
| I'd trade length of lifespan for quality in a heartbeat.
| Getting old is not very pleasant. I'm already starting to
| feel the creaks and decline merely in my mid 40. I'd love to
| have more time now but do have to work and when/if I will be
| able to retire I will be too worn out and lacking the desire
| to do the things I'd do know with that time. I'd be content
| to live healthily till say 65-70. My mom who is at that age
| is saying that she used to say the same thing when she was
| young but she no longer things like that. I guess we all do
| have some survival instinct kicking in no matter what we
| rationalize prior.
| r00fus wrote:
| Why does quality and lifespan have to be a dichotomy? In
| fact the more I think about it, living a quality lifestyle
| often leads to longer life (eating healthy, keeping fit,
| having meaningful friendships).
|
| Both my wife and I have signed the papers to decline
| extended life in a vegetative state and have confirmed our
| desires with our kids.
| fnordpiglet wrote:
| I care more about being healthier longer. And I'd like that to
| last as long as I can and not a lot longer necessarily. It's
| because I love life because it's life, and wouldn't mind if it
| went on for a long time. I could learn so many things.
|
| But, even if it's 60 years I want them to be healthy. So I do
| the things I am supposed to to age more slowly because aging is
| causative to ill health. My things I do is eat reasonable
| amounts of healthy food and exercise regularly. I supplement a
| few things like magnesium and taurine, that I specifically do
| better taking than not.
|
| But if they came out with a "never age until you die" pill I
| would take it immediately.
|
| But I think you're confusing long life with long health span. I
| don't think anyone dreams of living a long full life is hellish
| degenerative ill health.
| riehwvfbk wrote:
| So who will pay for your long healthy life? The default
| answer is: you will, by working longer. Any other answer has
| this problem: why is this magic source of funds not currently
| available to cover even our current shorter lifespans?
|
| OK, so we've established that you have to continue working.
| Are you sure that you as a geriatric man on artificial life
| extension will be competitive with a younger guy who can go
| crazy and use the same tech to, say, never sleep - never mind
| that he'll die at 40? And even if we aren't talking extremes:
| you as a pill-supported walking corpse have to be ever
| vigilant of your own mortality. Someone younger can afford to
| take more risks.
| daedrdev wrote:
| Your argument is easily applied to all medical
| advancements, do you think we should stop using
| antibiotics? Vaccines? Maybe you should let the individuals
| determine what's best for themselves instead to trying to
| prescribe your strange anti capitalism ideology for them.
|
| Anyway medical research is focused on giving us on better
| quality of life as we age, which is what people objectively
| value, not whatever you think they are trying to do.
| logifail wrote:
| > Anyway medical research is focused on giving us on
| better quality of life as we age
|
| Polite correction: medical research is focussed on
| returns for those funding said research.
|
| Treating Americans is definitely a cash-cow for Big
| Pharma, indeed if a potential new drug can't/won't make
| it past the FDA then it will likely be killed off
| regardless of what the rest of the world might
| want/need/approve.
|
| Check out US healthcare spend per capita compared with
| everywhere else on the planet.
|
| (Source: friend in Big Pharma)
| mullingitover wrote:
| The bigger problem with extending lifespans beyond what
| evolution has optimized for is that you end up competing
| against your offspring for resources, and you give pathogens a
| non-moving genetic target to attack (which defeats the whole
| point of sexual reproduction).
| inglor_cz wrote:
| "you end up competing against your offspring for resources"
|
| This was relevant in the pre-agriculture era. We _already_
| live in densities several orders of magnitude higher than
| evolution optimized us for.
|
| I am more concerned about the somewhat artificial _societal
| resources_ , such as top jobs. We might get a very ossified
| elite. We almost saw a presidential election with two ancient
| guys competing. With longevity widespread, this may become a
| pattern.
|
| "you give pathogens a non-moving genetic target to attack"
|
| True, but we generally try to manage new infectious diseases
| by scientific means, not by "0.6 per cent of population is
| resistant to this, let the rest croak". See: AIDS, Covid.
| mullingitover wrote:
| > This was relevant in the pre-agriculture era. We already
| live in densities several orders of magnitude higher than
| evolution optimized us for.
|
| I mean, keep in mind that we're living in a snapshot of
| time that's very much not stable or sustainable. It's like
| we're all embers born in a massive forest fire that started
| a few days ago. Everything seems normal and stable for us
| in this situation because our frame of reference is
| effectively a few seconds. However, this forest fire will
| eventually consume all the available fuel and things will
| return to baseline, no matter how hard we fantasize that
| we're going to somehow spread the forest fire to other
| planets.
|
| Any temporary victories we've made over evolution are just
| that. We've already seen how absolutely vicious pathogens
| can be toward monoculture biomasses. Just ask the Gros
| Michel banana.
| inglor_cz wrote:
| Yeah, of course tomorrow a global plague may eradicate us
| all, or "all except Sentinelese people".
|
| Nevertheless, looking at our prehistory, the worst
| bottleneck of the human race was probably some 900
| thousand years ago, way, way before we had anything
| resembling civilization.
|
| https://www.nhm.ac.uk/discover/news/2023/august/human-
| ancest...
|
| So, at least for me, the question of whether we are more
| resilient as civilization vs. as primitive people in
| their pristine state, is very much open. Too many people
| seem to be sure that going with the natural flow is long-
| term better. But it feels a bit like the Noble Savage
| myth reiterated for current sensibilities.
| lottin wrote:
| What makes you think that our current life expectancy is
| optimal?
| jjk166 wrote:
| Not if your offspring also live longer.
|
| You have kids at 1X, Grandkids at 2X, die at 3X, doesn't
| matter if X=25 or X=30 or X=100, the population dynamics are
| the same.
| willcipriano wrote:
| Are you the sort of person who feels life is awesome?
|
| Knowing the name of a assisted suicide company off the top of
| your head seems to suggest not.
|
| If you were, why would you want that to end?
| riehwvfbk wrote:
| The people who want to extend their lives are the ones whose
| lives tend to be pretty good. The CEO plotting world domination
| kind of archetype. The rest of us are expected to be expendable
| biorobots who serve them. Unfortunately, this won't play out
| the way their fantasies tell them. The rich and powerful will
| be trapped by the need to always maintain their fragile lives.
| This in turn will slow down progress and open up the gates to a
| younger and more daring group to come to power.
| datavirtue wrote:
| This is true. Shifting a populations life expectancy up to
| suspend biological aging would be a panic moment for most
| governments that are tied to huge benefit systems based on
| age. Good luck changing the retirement age, again.
| gamepsys wrote:
| Life is great, who wouldn't want more of it?
|
| I'm old enough to see some the advances in medical care
| different family members were able to receive when they became
| very ill over the decades. I'm young enough to be optimistic
| that when it's my turn the treatments available will be even
| more significant.
|
| There's a certain quality of life I wouldn't want to spend a
| prolonged time in. I understand your point about not wanting to
| be in bad health. Most of the activities I do that will likely
| prolong my life (diet, exercise, manage stress, build social
| bonds, supplements, pharmacology, screenings) will also
| increase my likelihood of prolonging the amount of time I have
| in good health.
|
| Why am I interested in living longer? I think it's better than
| the alternative.
| darby_nine wrote:
| > I think it's better than the alternative.
|
| I mean, why? Longer lives are not necessarily any happier. In
| fact, old age seems pretty physically miserable.
| gamepsys wrote:
| There's miseries in all stages of life. I've known people
| that still enjoyed life into their 80s and even 90s. I'm
| not very afraid of being physical uncomfortable, and I
| enjoy being here enough to want to fight for more time.
| elzbardico wrote:
| This is personal and depends on your perspectives.
| Obviously the people who want to live longer don't share
| the same point of view as you. And it is ok, as long as you
| are not forced to adopt their point of view and vice-versa.
| elzbardico wrote:
| Nobody expects to live longer and have dementia. People are
| betting that they will escape that and there's a good
| probability that they will do. Not to mention that if you are
| around your 30s or 40s it would be terrible to not care about
| your general health just to find out in the next 10 or 20 years
| that science found a cure to dementia but now your body is too
| much fucked to take advantage of that.
| logifail wrote:
| > Nobody expects to live longer and have dementia
|
| I think we can generalise that statement to "nobody expects
| to have dementia". Until you get it :/
|
| There are people taking lots of vitamins, but with apologies
| to any vitamin-takers, that hypothesis seems to have been
| thoroughly debunked.
|
| _For healthy adults, taking multivitamins daily is not
| associated with a lower risk of death_
| https://www.nih.gov/news-events/news-releases/healthy-
| adults...
| elzbardico wrote:
| Living is risky, yeah, I know it. A lot of it is a fucking
| gamble, your profession, the place you decide to live, the
| people you enter relationships with.
|
| Nothing is assured.
|
| Yeah, maybe we will be all unemployable and miserable due
| to LLMs taking our jobs and failing to create others. Maybe
| we shouldn't have reproduced as our kids will never get to
| become adults due to a nuclear war or a fucking serious
| pandemic with a virus that will make SARS-COV-2 look like
| nothing.
|
| Who knows?
| klingoff wrote:
| Cabbage also doesn't work, but what does that have to do
| with a theory that:
|
| Metformin exerts a substantial neuroprotective effect,
| preserving brain structure and enhancing cognitive ability.
|
| We obviously want additions or replacements to physical and
| mental exercise depending on how much we get.
| yieldcrv wrote:
| I don't want to live longer _with dementia_
|
| I want the entire system to have longer maintenance and repair:
| skin smooth, head of hair, muscles not atrophied, bones not
| brittle, oxygenated blood circulating and keeping a brain well
| functioning without its own independent deterioration, risk of
| cancer mitigated, but also easily repairable if its occurring
|
| I look at the London borough checklist of what people died from
| in the 1600s, and it makes me optimistic that the things people
| currently die of will be solved
|
| I just don't want to be felled by _those_ things. Its nice that
| solving for them includes a high probability of centenarian
| lifespans, I'm fine crossing that bridge when we get there.
| pdimitar wrote:
| Why are you conflating long lifespan with miserable last 10-20
| years of the life?
|
| I aspire to be like that French gym trainer who was in near-
| perfect health and an optimal presence of mind at 96 years old
| when he died suddenly (I think of heart attack).
| elzbardico wrote:
| I find life awesome. I truly fucking enjoy it. I am not rich, I
| can't retire and probably will never be able to do so, but I
| also enjoy my work even if not all the time. I think the world
| is moving towards a terrible inflexion point, I think we are in
| a fucking crisis right now, and still, fuck that. I don't want
| to leave this boat.
|
| Now that said, I completely accept that not everyone shares my
| point of view, and I also accept that probably I wouldn't
| understand their reasons for doing so.
|
| Maybe you should stop worrying about it. Some people would
| eagerly take any opportunity to live a few more years, it makes
| no sense to you, but it makes to them. It is not like they are
| forcing you to also live more than what you want.
| Unbeliever69 wrote:
| I totally get where you're coming from. I voluntarily left
| the workforce and now we live off my wife's income as a
| public school teacher. She's got about 15 years until
| retirement, and while we're not rich, we're definitely
| comfortable. Surprisingly, we've managed to do better
| financially on a single income than we did with two.
|
| Leaving the traditional workforce was an easy decision for
| me. COVID had me working from home, and my startup didn't
| make it through the pandemic--raising capital was tough. Once
| I experienced working from home, I knew I couldn't go back to
| the office or work for anyone else.
|
| I feel the same way about retirement. While my wife supports
| us financially, I support her by managing the household. I
| take care of the pets, make her lunch, clean, help with her
| lessons and emails, and handle groceries and errands. I
| really enjoy this role. It frees me up to work on personal
| projects like novel-writing and developing a SaaS product I'm
| passionate about.
|
| I get a lot of satisfaction from making my wife's life
| easier, especially since being an elementary school teacher
| is no walk in the park. Thanks to my support, she's been able
| to raise over $60k for a unique program at her school in just
| two years. She's sharing her success stories at conferences
| worldwide, and seeing her thrive makes me happy too.
|
| I'm not spending my time golfing or vacationing. I keep my
| mind sharp and enjoy the work I do. Yes, I worry about the
| future--like the fear of being so sick that I become a
| burden, and no, I don't have enough saved up for that
| possibility.
|
| I feel like my generation (X) is in a tricky spot, but for
| now, I'm content.
| rscho wrote:
| IMO, americans are very afraid of death, for some reason. Much
| more so than europeans or Asians, in my experience. So there's
| a culture of lasting as long as possible, including through
| very debilitating treatment. It was my biggest surprise from a
| healthcare culture standpoint, when I went to practice in the
| USA.
| dgfitz wrote:
| Wow. Hope you went back to wherever you came from.
|
| What a fucked up thing to say.
| EVa5I7bHFq9mnYK wrote:
| What he is saying is true, doctors and everyone else
| involved try to squeeze as much money as possible from
| dying people.
| rscho wrote:
| I don't really have a comparative opinion about that.
| What I mean is that I've seen countless examples of US
| patients and docs willing to go to extremes of treatment
| that would be considered unreasonable elsewhere. But I
| was just a bloke in one big university hospital, so YMMV
| I guess. Still, the culture gap was pretty surprising.
| asimovfan wrote:
| What's fucked up about it? I didn't get it?
| dgfitz wrote:
| That American humans are more scared of dying than other
| humans. Almost seems... well...
| homebrewer wrote:
| Read "Being Mortal" and you might come around to a very
| different viewpoint.
| rscho wrote:
| Yes, I went back to a country with socialized medicine
| where patients as well as doctors are still relatively
| courteous to each other. It was a huge relief to leave the
| US, professionally speaking. BTW, I don't really get why
| you're so riled up.
| stickfigure wrote:
| If my doctor said "don't be afraid of death", I would get
| a new doctor.
| rscho wrote:
| It's natural to be afraid. I'm afraid too, at times. But
| people are only willing to suffer so much. In this
| regard, US people offer an interesting contrast: they
| tend to view as normal not to suffer at all in routine
| care (minor surgery, for example), but are willing to
| accept an incredibly bad quality of life in desperate
| situations. In Europe for example, it tends towards the
| opposite. Again, I'm just one guy. YMMV.
| numpad0 wrote:
| Doubt it, besides there aren't a lot of reasons for us all to
| not just casually choose death had it been for humans' innate
| fear of death, which I think is kind of good thing.
| imarg wrote:
| I think this comment generalizes too much. I do not think
| Europeans are all the same on this (and probably Asians too).
|
| As an example I have the impression that what you wrote is
| true for Dutch people (I don't know if it's true but I've
| heard/read they are more on the side of making elderly people
| comfortable in their last moments rather than trying to treat
| them with expensive procedures).
|
| While here in Greece we do try to prolong the life of even
| the most hopeless situations (that might be changing). It's
| not rare to have our elderly parents/grandparents bedridden
| at home for years.
|
| Of course I might be generalizing also.
| rscho wrote:
| Yeah. It's just my experience. Not claiming anything beyond
| my personal perception. In my country, we also tend to put
| quality of life first.
| 4star3star wrote:
| Partly, I think that the culture is more affected by the lack
| of history than most people realize. If you've lived in
| Europe, and I'm sure elsewhere, you understand your mortality
| implicitly from the centuries-old buildings and streets. At
| least that's what I got out of it.
| eqvinox wrote:
| "decelerates aging clock" implies slowing down processes of
| decreasing health, not just living longer in a frail state at
| the end. In particular if you click the link, the first thing
| it says is:
|
| * Metformin prevents brain atrophy, elevating cognitive
| function in aged male primates * Metformin slows the pace of
| aging across diverse male primate tissues * Metformin
| counterparts neuronal aging, delivering geroprotection via Nrf2
| in male primates
|
| It doesn't even say you'd live longer. If I could get something
| that doesn't extend my life at all, just keeps my brain fresher
| into my old age, I would jump on that as well.
| inglor_cz wrote:
| People are interested in _slowing aging_ , which means _living
| longer in good health_.
|
| The ultimate goal would be negligible senescence.
|
| Dementia and other chronic diseases that plague our end days
| now are consequences of aging. They don't just come randomly,
| they are a result of the aging process, which is nothing but
| slow deterioration, possibly a programmed one.
|
| Of course people want to get rid of that.
| desireco42 wrote:
| I think you are looking at this the wrong way. I turned 50
| recently. I have ADHD and I was fairly immature for a long
| time.
|
| I finally understand so much about life, I genuinely am helping
| a lot of people and to be honest, want to continue living and
| enjoying life.
|
| There are so many books to read, experiences to have.
|
| Yet I can feel that my body is no longer how it used to be.
|
| If there was something that could bring back to clock, 5-10
| extra years. Totally worth it.
| StanislavPetrov wrote:
| I certainly wouldn't want to live forever one way or the other,
| but most people who talk about living longer mean slowing or
| halting the aging process, not simply surviving more years as a
| decaying husk.
| jjk166 wrote:
| Your Father and Father-in-laws conditions are due to the
| process of aging, not the number of years they have lived. It
| is the process of aging which anti-aging advocates want to
| delay or eliminate. Living longer doesn't mean tacking on years
| at the end, continuing the aging process for longer; it means
| adding years to the middle before aging begins, as well as
| lessening the effects of aging when that time eventually comes.
| monkeyfun wrote:
| To flip your question around, why are you living right now?
|
| I developed a severe intestinal disorder in my 20s. Some people
| can get it or ones like it in their teens, others their 30s,
| 40s, 50s, etc. and many won't ever develop such issues,
| although they're reasonably common to a less severe extreme
| than my case.
|
| Knowing this, and that I could explain my disorder for years
| being debilitating and putting me in agonizing pain and
| suffering, why would you want to live any longer when it
| _could_ happen to you too?
|
| Not everyone is going to develop such cognitive disorders as
| you discuss, and often they're a result of complex genetic and
| lifestyle factors, as well as likely having to do with aspects
| of aging like reduced function of organs. So it's quite
| possible these diseases and disorders aren't inevitable simply
| as a consequence of living long enough, or could be treated and
| reversed as medical science advances.
|
| If I sound bitter by the way, I am slightly, but do mean for
| this to still be conveyed productively.
|
| To hear someone asking "why are people interested in living
| longer?" makes me genuinely want to know why you're interested
| in living longer. You could die right now and free up resources
| for the rest of us, or donate resources to younger people than
| you who are in need, or simply give it to me since I'm neither
| senile nor old (not even 30) nor have a family history of such
| disorders as you mentioned, nor would I put it to poor use.
|
| I suspect you want to live. The simple fact is, it's that same
| desire to live and to continue enjoying life to the fullest
| that makes those of us with foresight interested in prolonging
| our healthy lives.
| huqedato wrote:
| My PhD coordinator advised me to approach any study originating
| from China with the utmost caution even if peer reviewed.
| non- wrote:
| So if Metformin is used to treat high blood sugar levels, would
| we get the same cognitive benefits by just consuming less sugar?
|
| Can't see the full paper to see if they compared the results of
| metformin vs a low-sugar diet.
|
| EDIT: Already brought up and discussed here
| https://news.ycombinator.com/item?id=41522931#41523725
| aanet wrote:
| I haven't read the CELL paper yet (would love to, if somebody has
| a PDF to share).
|
| But I'm surprised I yet haven't seen a mention of Dr. Michael
| Greger's book [1] _How Not to Die_ , which does an excellent job
| of elaborating how various diseases -- including cardiovascular
| diseases, diabetes, etc -- result in death.
|
| I found it immensely helpful in plugging a lot of holes in my
| understanding of my own health (FWIW: 40s, no chronic diseases,
| but tendency towards high(er) A1C, cholesterol)
|
| He has subsequently released other books -- How Not To Age, How
| Not to Diet, etc -- which one might call as capitalizing on the
| trend, not to put too fine a point on it. [However, I do find his
| books, videos and discussions quite informative, and not too
| technical, without going into the hyper-masculine, pseudo-
| science-y word salad territory waded into by, say, Huberman.]
|
| There's a brief video [2] on side effects of metformin as a life
| extension drug, which seems relevant to the CELL paper above.
|
| [1] https://nutritionfacts.org/book/how-not-to-die/ [2]
| https://nutritionfacts.org/video/side-effects-of-metformin-a...
| KaiserPro wrote:
| My wife did geriatric care when she was a student doctor. When I
| told her about this article she said and I quote: "I've met loads
| of old people on metformin, its not done anything for them"
| unsupp0rted wrote:
| Isn't this like saying "I've seen a lot of pilots come back
| with damage to this part of the fuselage"?
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