12 ms·

Metformin decelerates aging clock in male monkeys

205 points by tortilla 2y ago

Gelob 2y ago
[flagged]
- deleted 2y ago
  [deleted]
- altgeek 2y ago
  This is a common side effect. Try the extended-release form, i.e. Glucophage XR.
  - deleted 2y ago
    [deleted]
- jokowueu 2y ago
  Much less of an issue with XR and after a few months you won't feel any discomfort Most annoying thing for me was the metal taste in my mouth for a few months Had to take it for my reactive hypoglycemia
- leptons 2y ago
  Probably not that common, as my anecdotal ass has been on Metformin for many years and there's been zero side effects. I'm quite regular. In the past I had plenty of stomach/stool issues, but I've found that more fiber in my diet fixed that up nicely.
  - zamadatix 2y ago
    I don't know about shitting your pants levels bad but gastrointestinal side effects are very common with Metformin, on the order of ~30% taking it will have... quite a time at the start (I was definitely one). My doctor said something like 10%-15% of diabetics end up having to move to something else because while it generally gets better for most after taking it a while, it doesn't for all. On the flipside, many take it and would never even guess that could be a side effect. Just luck of the draw.
- deleted 2y ago
  [deleted]
ninetyninenine 2y ago
>https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.718942/full https://www.frontiersin.org/journals/endocrinology/articles/... Data is controversial. It's not "not enough" data or anything like that either.
- MarkusQ 2y ago
  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 2y ago
  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 2y ago
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 2y ago
  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 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 2y ago
    You can safely remove the quotes around 'glucose' and replace "high blood sugar" with 'glycemia'
  - ochronus 2y ago
    Plus one in this, I reverted my Type II diabetes in 3-ish months by radically cutting out carbs (including sugars) and adding more protein to my diet. My lab results have been consistently in the "OK" range since.
fnord77 2y ago
metformin can also cause gastroparesis, which is a nasty condition I wouldn't wish on anyone.
- toomuchtodo 2y ago
  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-diabetes-drug.html https://med.stanford.edu/news/all-news/2022/03/birth-defects... https://www.acpjournals.org/doi/10.7326/M21-4389 https://www.acpjournals.org/doi/10.7326/M21-4389
  - antisthenes 2y ago
    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 2y ago
  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 2y ago
    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 2y ago
      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.
deleted 2y ago
[deleted]
generalizations 2y ago
https://en.wikipedia.org/wiki/Metformin 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?
- deleted 2y ago
  [deleted]
- arcticbull 2y ago
  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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299044/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/ [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841986/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841986/
  - riehwvfbk 2y ago
    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.
dewarrn1 2y ago
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 https://www.afar.org/tame-trial
- matthewdgreen 2y ago
  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 2y ago
    > Also I am not a monkey [Citation Needed]
  - leptons 2y ago
    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".
    - snailb 2y ago
      Same here, 2kmg every day split between 1 in the morning and one in the evening. I did have Diarrhea at the beginning but that went away in a few days. I am more forgetful now and a little bit more irritated at times, and I've heard this could be related to Metformin.
  - falcolas 2y ago
    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.
testfrequency 2y ago
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 2y ago
  Metformin is off patent and is easy to make. You will have no problems.
  - fzingle 2y ago
    So is insulin. But at least in the US, it is expensive.
    - adrianN 2y ago
      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 2y ago
      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 2y ago
      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-details/lilly-cuts-insulin-prices-70-and-caps-patient-insulin-out-pocket 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.
birriel 2y ago
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-program-itp/supported-interventions https://www.nia.nih.gov/research/dab/interventions-testing-p...
- tines 2y ago
  Mice vs monkeys?
  - trhway 2y ago
    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 2y ago
  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 2y ago
    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 2y ago
  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/36173858/ https://pubmed.ncbi.nlm.nih.gov/34666007/ https://pubmed.ncbi.nlm.nih.gov/34666007/ https://pubmed.ncbi.nlm.nih.gov/34552269/ https://pubmed.ncbi.nlm.nih.gov/34552269/
tocs3 2y ago
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 2y ago
  What are the other options?
  - tocs3 2y ago
    https://diabetes.org/health-wellness/medication/oral-other-injectable-diabetes-medications https://diabetes.org/health-wellness/medication/oral-other-i...
- bityard 2y ago
  If you are open to controlling Type II diabetes by changing your diet, look up anything by Dr. Eric Westman.
  - UncleSlacky 2y ago
    Also look into the Newcastle Protocol and Prof. Roy Taylor: https://www.ncl.ac.uk/magres/research/diabetes/reversal/#publicinformation https://www.ncl.ac.uk/magres/research/diabetes/reversal/#pub...
- shaftway 2y ago
  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".
logifail 2y ago
(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 2y ago
  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 2y ago
    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 2y ago
  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 2y ago
huqedato 2y ago
My PhD coordinator advised me to approach any study originating from China with the utmost caution even if peer reviewed.
- rahimnathwani 2y ago
  It's funny you mention this the same data the Data Colada guys won their motion to dismiss.
non- 2y ago
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 https://news.ycombinator.com/item?id=41522931#41523725
deleted 2y ago
[deleted]
aanet 2y ago
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/ https://nutritionfacts.org/book/how-not-to-die/ [2] https://nutritionfacts.org/video/side-effects-of-metformin-as-a-life-extension-drug/ https://nutritionfacts.org/video/side-effects-of-metformin-a...
KaiserPro 2y ago
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 2y ago
  Isn’t this like saying “I’ve seen a lot of pilots come back with damage to this part of the fuselage”?
- 7e 2y ago
  This is why we don't do science with anecdotes.
  - KaiserPro 2y ago
    While yes, I agree, what I'm trying to point out is there is a large population of people who regularly take metformin for a number of reasons in the UK. If there was a strong correlation in cognitive improvement we should be able to detect it now.
kamaal 2y ago
May be a doctor can answer this. Will fasting slow down aging? Ideally it should cause the same effect?
Randypea 2y ago
This study shows the combination of Metformin and Everolimus( Rapymyacin) is more effective at cancer than either alone. More research is needed. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464161/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464161/ I have NET cancer and am taking Everoliumus. I am thinking about recruiting other NET cancer patients to do an informal test of Metformin and Everolimus( Rapymyacin). Is there any structure or web site or other tools to help us with this?

205 points by tortilla 2y ago

Gelob 2y ago

[flagged]

deleted 2y ago
[deleted]
altgeek 2y ago
This is a common side effect. Try the extended-release form, i.e. Glucophage XR.
- deleted 2y ago
  [deleted]
jokowueu 2y ago
Much less of an issue with XR and after a few months you won't feel any discomfort Most annoying thing for me was the metal taste in my mouth for a few months Had to take it for my reactive hypoglycemia
leptons 2y ago
Probably not that common, as my anecdotal ass has been on Metformin for many years and there's been zero side effects. I'm quite regular. In the past I had plenty of stomach/stool issues, but I've found that more fiber in my diet fixed that up nicely.
- zamadatix 2y ago
  I don't know about shitting your pants levels bad but gastrointestinal side effects are very common with Metformin, on the order of ~30% taking it will have... quite a time at the start (I was definitely one). My doctor said something like 10%-15% of diabetics end up having to move to something else because while it generally gets better for most after taking it a while, it doesn't for all. On the flipside, many take it and would never even guess that could be a side effect. Just luck of the draw.
deleted 2y ago
[deleted]

ninetyninenine 2y ago

>https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.718942/full https://www.frontiersin.org/journals/endocrinology/articles/... Data is controversial. It's not "not enough" data or anything like that either.

MarkusQ 2y ago
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 2y ago
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 2y ago

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 2y ago
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 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 2y ago
  You can safely remove the quotes around 'glucose' and replace "high blood sugar" with 'glycemia'
- ochronus 2y ago
  Plus one in this, I reverted my Type II diabetes in 3-ish months by radically cutting out carbs (including sugars) and adding more protein to my diet. My lab results have been consistently in the "OK" range since.

fnord77 2y ago

metformin can also cause gastroparesis, which is a nasty condition I wouldn't wish on anyone.

toomuchtodo 2y ago
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-diabetes-drug.html https://med.stanford.edu/news/all-news/2022/03/birth-defects... https://www.acpjournals.org/doi/10.7326/M21-4389 https://www.acpjournals.org/doi/10.7326/M21-4389
- antisthenes 2y ago
  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 2y ago
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 2y ago
  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 2y ago
    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.

deleted 2y ago

[deleted]

generalizations 2y ago

https://en.wikipedia.org/wiki/Metformin 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?

deleted 2y ago
[deleted]
arcticbull 2y ago
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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299044/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/ [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841986/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841986/
- riehwvfbk 2y ago
  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.

dewarrn1 2y ago

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 https://www.afar.org/tame-trial

matthewdgreen 2y ago
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 2y ago
  > Also I am not a monkey [Citation Needed]
- leptons 2y ago
  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".
  - snailb 2y ago
    Same here, 2kmg every day split between 1 in the morning and one in the evening. I did have Diarrhea at the beginning but that went away in a few days. I am more forgetful now and a little bit more irritated at times, and I've heard this could be related to Metformin.
- falcolas 2y ago
  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.

testfrequency 2y ago

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 2y ago
Metformin is off patent and is easy to make. You will have no problems.
- fzingle 2y ago
  So is insulin. But at least in the US, it is expensive.
  - adrianN 2y ago
    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 2y ago
    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 2y ago
    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-details/lilly-cuts-insulin-prices-70-and-caps-patient-insulin-out-pocket 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.

birriel 2y ago

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-program-itp/supported-interventions https://www.nia.nih.gov/research/dab/interventions-testing-p...

tines 2y ago
Mice vs monkeys?
- trhway 2y ago
  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 2y ago
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 2y ago
  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 2y ago
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/36173858/ https://pubmed.ncbi.nlm.nih.gov/34666007/ https://pubmed.ncbi.nlm.nih.gov/34666007/ https://pubmed.ncbi.nlm.nih.gov/34552269/ https://pubmed.ncbi.nlm.nih.gov/34552269/

tocs3 2y ago

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 2y ago
What are the other options?
- tocs3 2y ago
  https://diabetes.org/health-wellness/medication/oral-other-injectable-diabetes-medications https://diabetes.org/health-wellness/medication/oral-other-i...
bityard 2y ago
If you are open to controlling Type II diabetes by changing your diet, look up anything by Dr. Eric Westman.
- UncleSlacky 2y ago
  Also look into the Newcastle Protocol and Prof. Roy Taylor: https://www.ncl.ac.uk/magres/research/diabetes/reversal/#publicinformation https://www.ncl.ac.uk/magres/research/diabetes/reversal/#pub...
shaftway 2y ago
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".

logifail 2y ago

(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 2y ago
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 2y ago
  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 2y ago
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 2y ago

huqedato 2y ago

My PhD coordinator advised me to approach any study originating from China with the utmost caution even if peer reviewed.

rahimnathwani 2y ago
It's funny you mention this the same data the Data Colada guys won their motion to dismiss.

non- 2y ago

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 https://news.ycombinator.com/item?id=41522931#41523725

deleted 2y ago

[deleted]

aanet 2y ago

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/ https://nutritionfacts.org/book/how-not-to-die/ [2] https://nutritionfacts.org/video/side-effects-of-metformin-as-a-life-extension-drug/ https://nutritionfacts.org/video/side-effects-of-metformin-a...

KaiserPro 2y ago

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 2y ago
Isn’t this like saying “I’ve seen a lot of pilots come back with damage to this part of the fuselage”?
7e 2y ago
This is why we don't do science with anecdotes.
- KaiserPro 2y ago
  While yes, I agree, what I'm trying to point out is there is a large population of people who regularly take metformin for a number of reasons in the UK. If there was a strong correlation in cognitive improvement we should be able to detect it now.

kamaal 2y ago

May be a doctor can answer this. Will fasting slow down aging? Ideally it should cause the same effect?

Randypea 2y ago

This study shows the combination of Metformin and Everolimus( Rapymyacin) is more effective at cancer than either alone. More research is needed. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464161/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464161/ I have NET cancer and am taking Everoliumus. I am thinking about recruiting other NET cancer patients to do an informal test of Metformin and Everolimus( Rapymyacin). Is there any structure or web site or other tools to help us with this?