Metformin decelerates aging clock in male monkeys
cell.com
cell.com
> 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?
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/
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.
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).
Prior to Iodized salt, Switzerland was suffering from a rash of people with Goiter, which is disfiguring and decreases your quality of life, and also a large population with cretinism which causes stunted growth and mental retardation.
Then, they introduced iodized salt, and those issues which used to be somewhat prevalent only 100 years ago are practically nonexistent now.
https://swissfederalism.ch/en/100-years-salt-iodination-swit...
The hard way of finding out how bad polished white rice is for you - https://www.atlasobscura.com/articles/rice-disease-mystery-e...
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?
https://www.fractyl.com/fractyl-health-demonstrates-signific...
https://recursiveadaptation.com/p/the-growing-scientific-cas...
> The consistency that I'm hearing from all across patient groups is gain of control, whereas previously, there was a loss of control… All of a sudden they're able to step back and say, 'oh, well I had this shopping phenomenon that was going on, gambling, addiction, or alcoholism, and all of a sudden, it just stopped,' -- Dr. Gitanjali Srivastava, Vanderbilt Medical Center
https://news.ycombinator.com/item?id=40357197 (comment from u/comova)
> 1. GLP-1 drugs appear to dramatically reduce addictive drive across substances. 2. GLP-1 drugs can reach vastly more patients than existing medications and they have positive mental health benefits for anxiety and depression. 3. This is our first ever opportunity to make a big dent in the addiction crisis, which kills 770,000 people a year between opioids, cigarettes, and alcohol.
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.
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.
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).
found no reduction in all-cause mortality by metformin treatment.
Roughly speaking, they compared:
- people with diabetes that was treated with Metformin
- their twins who didn't have diabetes and were not taking Metformin
As far as I can tell, they didn't isolate the impact of metformin alone (vs the combined impact of having diabetes and taking metformin).
Have I misunderstood?
“individuals with Type 2 diabetes who initiated metformin monotherapy as their first-line treatment exhibit lower mortality over follow-up compared to the general population WITHOUT diabetes.” (emphasis added)
That is an exceedingly strong and apparent wrong claim. Mortality rates are worse among metformin treated subjects.
Of course there is no perfect control of the type we might want in principle (metaformin-treated non-diabetics or non-treated Type 2 diabetics).
However the first type of these case-controls studies has been done in genetically diverse mice by the NIA ITP team and the results are reasonable strong and negative.
My point is that you seem to be saying that the Keys study shows that metformin doesn't increase life expectancy. I am basing this understanding on two things you wrote:
"found no reduction in all-cause mortality by metformin treatment"
"Mortality rates are worse among metformin treated subjects."
But the Keys study does not show that Metformin doesn't increase life expectancy (or reduce all-cause mortality). It shows that Metformin isn't enough to counteract the impact (on lifespan) of diabetes. But it seems to say nothing about whether people (whether diabetic or not) would live longer with metformin or without.
I realize the Keys study isn't the only piece of research in this area. But the topic of my original comment (and this one) are simply that particular study, and what you say it shows.
If I have misunderstood anything I am happy to be corrected/educated.
A person (and the processes in their body) goes through cycles on a daily and long-term basis. One is not constantly eating, exercising, and growing.
Muscle mass and strength are not the same thing, though they are highly correlated. I believe most studies on the elderly use measures like grip strength, which is a proxy for frailty.
The elderly don't have the same capacity for growth or energy. However, they can avoid wasting away by remaining active. They certainly benefit from autophagy as it clears senescent cells. Perhaps this shift is the body's way of reducing the risk of cancer.
As an aside, a curious data point is that men have shorter lifespans than women on average. There are likely several reasons for this, but I wonder if this has to do with the hormonal effect on mTOR. Perhaps our ability to grow is finite, and excessive activation of mTOR "runs out the clock" faster.
TL;DR: It's a balancing act.
Are typical monkeys obese like typical Americans?
Essentially: put them in small cages for years, give them a nearly unlimited supply of food, and give them nothing to do. Terrible.
This video actually helped to motivate me to get into meal prepping, and significant weight loss.
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.
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.
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...
Maybe try 10mg doses but the 5g should do it.
Inflammation bitch slap.
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?
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...
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.
> 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.
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.
[Citation Needed]
I am more forgetful now and a little bit more irritated at times, and I've heard this could be related to Metformin.
More like "the asshole! They're not called "Metfartmin" for nothing! If you want to live a long smelly life with no friends and certainly with no bed partner then Metformin may be the pill for you.
I told a friend about this drug's life-extension possibilities. We set out to meet at Starbucks but, prior to leaving, he took 2 x 500-mg Metformin (he's a diabetic and so has a prescription). An hour later he arrived and confessed that his tardiness was incurred when a fart was revealed to contain a lump. He had to return home to change his pants.
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
https://www.ncl.ac.uk/magres/research/diabetes/reversal/#pub...
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".
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
> 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...
E.g. cut out bad foods, any drugs, exercise regularly.
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.
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.
I think some drugs are more easily tolerated by the body if they are gradually introduced.
Is this an American game? What is it called? Who checks the quarters? How?
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...
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.
https://pubmed.ncbi.nlm.nih.gov/36173858/
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.
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.
Data is controversial. It's not "not enough" data or anything like that either.
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
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.
Ideally it should cause the same effect?
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...
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
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 :(
There's no point in living longer if your faculties are too degraded to enjoy it, you may as well just be dead.
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.
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.
If no one can ever know, I'm not sure I care. Transport me to cool places all you like.
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
...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...
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
I wear glasses, clothes, and my kids were born three months early. I, and they, were supposed to die.
...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.
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.
I can’t really think of any downside to having more healthy years. Yeah, do more stuff, see more things, learn more.
Why? Because it’s enjoyable.
And why do I need a reason?
> 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?
*I am not a doctor, but also I can correlate data without bias.
---
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
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.
Anti-aging is picking up now because there's a growing belief that significantly extending the healthy human lifespan is within scientific/technological reach.
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?
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" (!)
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?
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.
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.
It’s a good idea to live a healthy life, but you are merely shifting the odds. Many a health nut has hit 60 and found themselves with new problems every year, and each one is a small thing, but it adds up.
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.
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.
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.
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)
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.
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.
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.
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.
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?
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.
I mean, why? Longer lives are not necessarily any happier. In fact, old age seems pretty physically miserable.
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...
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?
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.
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.
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).
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.
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.
• 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.
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.
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.
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.
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.
I really hope my prescription costs and access to Metformin is not ruined by everyone’s quest to out live their children
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.
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.
(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.)