Metformin decelerates aging clock in male monkeys

https://www.cell.com/cell/abstract/S0092-8674(24)00914-0

by tortilla • 2 years ago

205 189 2 years ago

cell.com

ninetyninenine• 2 years ago

https://www.frontiersin.org/journals/endocrinology/articles/...

Data is controversial. It's not "not enough" data or anything like that either.

MarkusQ• 2 years 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• 2 years 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• 2 years 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• 2 years 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

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.

catlikesshrimp2• 2 years ago

You can safely remove the quotes around 'glucose' and replace "high blood sugar" with 'glycemia'

ochronus• 2 years 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• 2 years ago

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

toomuchtodo3• 2 years 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...

https://www.acpjournals.org/doi/10.7326/M21-4389

antisthenes• 2 years 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.

caseyy2• 2 years 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.

epasveer2• 2 years 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.

generalizations• 2 years ago

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?

arcticbull5• 2 years 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/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841986/

riehwvfbk6• 2 years 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.

sctb• 2 years ago

Do you have a sense of how different mTOR-related interventions stack up? As in, metformin vs rapamycin vs intermittent fasting?

robwwilliams10• 2 years ago

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).

tarsinge• 2 years ago

Interesting how this is the opposed of fitness recommendations where it’s all about mTOR activation to build muscle with protein or even pure leucine supplements. That would imply a strong inverse correlation between muscle mass and longevity, but I’m not aware of research showing this, even maybe the opposite. How do you explain this apparent paradox? Maybe the problem is mTOR over activation, not an intermittent one, kind of like insulin? In that case phases of muscle building with autophagy in between (ie intermittent fasting) could be the best of both.

onlyrealcuzzo• 2 years ago

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• 2 years ago

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.

dukeofdoom• 2 years ago

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.

bityard3• 2 years ago

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.

hinkley4• 2 years ago

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.

arcticbull5• 2 years ago

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...

dewarrn1• 2 years 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

matthewdgreen• 2 years 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• 2 years ago

Also I am not a monkey

[Citation Needed]

leptons• 2 years 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".

falcolas• 2 years 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.

robwwilliams10• 2 years ago

TAME has not yet been funded by NIA. Stay tuned.

aanet2• 2 years ago

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• 2 years 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

7e3• 2 years ago

Metformin is off patent and is easy to make. You will have no problems.

fzingle• 2 years ago

So is insulin. But at least in the US, it is expensive.

zamadatix• 2 years ago

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.

renewiltord2• 2 years ago

Artificial scarcity of these drugs is an intentional choice.

__MatrixMan__• 2 years ago

We need more garage chemists so that it can be a less consequential one.

DeonPenny• 2 years ago

More people taking medication lower price not increases it.

bityard3• 2 years ago

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• 2 years 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-p...

tines• 2 years ago

Mice vs monkeys?

trhway• 2 years 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.

hinkley4• 2 years 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.

robwwilliams10• 2 years 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.

robwwilliams10• 2 years 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/34666007/

https://pubmed.ncbi.nlm.nih.gov/34552269/

7e3• 2 years ago

Improving the genetic diversity of mouse models doesn't help you when a humans are far more complex, anyway. You may find a universal effect for a mouse, it's still a mouse. You're trying to fix the space shuttle by testing changes on automobiles.

tocs32• 2 years 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• 2 years ago

What are the other options?

tocs32• 2 years ago

https://diabetes.org/health-wellness/medication/oral-other-i...

bityard3• 2 years ago

If you are open to controlling Type II diabetes by changing your diet, look up anything by Dr. Eric Westman.

UncleSlacky• 2 years ago

Also look into the Newcastle Protocol and Prof. Roy Taylor:

https://www.ncl.ac.uk/magres/research/diabetes/reversal/#pub...

shaftway• 2 years 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".

catlikesshrimp2• 2 years ago

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• 2 years ago

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 !

datavirtue3• 2 years ago

House said you should always lie.

_qua• 2 years ago

Guidelines call for metformin first for most people, add ons from there are usually chosen based on the individual patient's comorbidities.

logifail9• 2 years 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• 2 years 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• 2 years 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.

ceejayoz5• 2 years 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.

highwaylights2• 2 years ago

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.

logifail9• 2 years ago

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...

tempestn• 2 years ago

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?

dangus2• 2 years ago

People want more healthy years.

logifail9• 2 years ago

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.

rileymat2• 2 years ago

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• 2 years ago

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-2• 2 years ago

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

iwontberude2• 2 years ago

• Metformin-associated lactic acidosis has an estimated death rate of up to 50%.

switchbak• 2 years ago

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.

a13n2• 2 years ago

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.

onemoresoop• 2 years ago

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.

fnordpiglet• 2 years ago

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.

riehwvfbk6• 2 years ago

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.

mullingitover2• 2 years ago

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_cz5• 2 years ago

"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.

lottin• 2 years ago

What makes you think that our current life expectancy is optimal?

jjk1663• 2 years ago

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• 2 years ago

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?

riehwvfbk6• 2 years ago

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.

datavirtue3• 2 years ago

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.

gamepsys2• 2 years ago

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• 2 years ago

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.

elzbardico4• 2 years ago

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.

logifail9• 2 years ago

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...

yieldcrv• 2 years ago

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• 2 years ago

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).

elzbardico4• 2 years ago

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• 2 years ago

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.

eqvinox• 2 years ago

"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_cz5• 2 years ago

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• 2 years ago

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.

StanislavPetrov2• 2 years ago

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.

jjk1663• 2 years ago

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• 2 years ago

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.

washadjeffmad• 2 years ago

The greatest challenge of chronic pain isn't necessarily the pain, but how it warps and taints parts of you beyond your control.

People who haven't experienced their failure are completely unaware of the incredible mechanisms of our evolution that keep us from suicide. They're also unaware of what choosing to live means in the face of the eventual erosion of those failsafes by pain.

It's like hurtling down the interstate at 70mph in heavy traffic and having the power steering go out. There's no sense of freedom and accomplishment in having to fight just to keep to your lane, only terror from all the parts of you that know how easily you'd crash if you stopped trying for even a few seconds. It's exhausting in every sense.

huqedato• 2 years ago

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

rahimnathwani3• 2 years ago

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

non-2• 2 years 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

aanet2• 2 years 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/ [2] https://nutritionfacts.org/video/side-effects-of-metformin-a...

KaiserPro2• 2 years 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• 2 years ago

Isn’t this like saying “I’ve seen a lot of pilots come back with damage to this part of the fuselage”?

7e3• 2 years ago

This is why we don't do science with anecdotes.

KaiserPro2• 2 years 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• 2 years ago

May be a doctor can answer this. Will fasting slow down aging?

Ideally it should cause the same effect?

Randypea• 2 years 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/ 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?

Metformin decelerates aging clock in male monkeys

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