“Intermittent fasting and/or caloric restriction extends mice lifespan.” is quite old news.
The reason mice are used in labs isn’t because they’re a good model of humans, but because they’re easy to bread and have short lifespans.
Studies of caloric restriction in monkeys didn’t cause lifespan extension, casting doubt on its effect in humans.
Peter Attia (best source of longevity science) wrote about this 5 years ago.
https://peterattiamd.com/calorie-restriction-part-iia-monkey...
Monkeys (more precisely chimpanzees) do not have fasting mechanisms. They never start fasting and go into ketosis, they just die from starvation after week or two. In tropics they have food available all year. They never venture far from food sources.
Humans (and other non-tropic animals like mice) have adaptation for seasonal food availability, and can go through extended fasting.
This should be higher up. Humans split from primates (including chimpanzees) roughly 5 million years ago. Early hominids only evolved the ability to store large amounts of fat and fast for extended periods of time in the Pleistocene, less than 2 million years ago. Any study done on calorie restriction using monkeys has a serious caveat. Mice offer a much better starting point for comparing metabolic activity.
A little typo: I think you meant to say humans split from *other apes and monkeys, not "primates".
Humans are part of the Primate order[0], as well as other great apes like gorillas, and chimpanzees too.
We (the Homo genus) did split from the Pan genus (chimpanzees & bonobos) 5 million years ago.
Yes, it should've been "from other (modern) primates"
You're kidding, right? I can see saying neither one tells you much about human beings, but saying monkey studies aren't relevant to human but mouse studies are just sounds bizarre.
When you frame it like that of course it sounds bizarre.
You just ignored the context of ketogenic metabolism being more similar in humans and mice than humans and chimpanzees.
"All models are wrong, but some are useful."
~ George Box
If you're specifically studying something that is a stark difference between other monkeys and apes on one side and humans on the other, studying monkeys and apes is obviously not a smart thing to do.
> This should be higher up.
As of right now, it's as high as could possibly be. Please don't suppose comments stay wherever they were when you wrote your comment. It looks silly.
(Other than that, reasonable observations - thank you!)
Maybe? What about rhesus monkeys?
Note that ketosis != fasting; ketosis == low carb, which can also be induced without fasting (but only by eating a low (near zero) carb diet). So are you sure you're not conflating 2 dimensions (how much we eat, vs what we eat)?
Funny enough, one of the reasons I respect Peter Attia, is that he's changed his mind several times, after new information came to light (i.e. he had an initial assumption based on weak evidence, then changed his opinion after he found stronger evidence). This is quite rare in general, an even rarer among the "influencers" (a.k.a. professional grifters).
The first time Peter Attia had to change his mind, is when his Nutrition Science Initiative (NuSI) collapsed. Long story short, his hypothesis was that carbs (or rather, the insulin response) make people obese, and that low carb diets drastically improve health. NuSi funded proper experiments to test this, i.e. they provided calorie-matched low-carb and non-low-carb diets. They failed to confirm the hypothesis.
https://www.wired.com/story/how-a-dollar40-million-nutrition...
I thought so too but this is newer research on monkeys based on a long running study since 1989 linked directly in the first sentence of the article: https://www.nature.com/articles/nature.2014.14963. That being said the Wisconsin study does have a fair amount of criticism in that they cut back on a diet composed 30% sugar from an all you can eat buffet so it’s unclear if it’s purely just stopping being overweight / reducing risk of diabetes or if there’s any other benefits.
FWIW as much as it’s fair to criticize the study design, an all you can eat buffet composed of 30% sugar is more or less par for the average American.
It’s not like we’re out here in the real world with a healthy and nutritionally balanced baseline. Most of us eat quite a bit of trash, so in the context of the real world the findings seem valid enough.
There’s a difference between “caloric intake reduces obesity related mortality causes like diabetes” and “caloric intake extends lifespan”. Even though they’re related, the latter is claiming everyone would benefit from it including those that aren’t obese and is fighting some kind of fundamental aging mechanism caused by eating while the former is just saying how to fix the American diet to fix obesity and diabetes.
What, if you don't eat the standard american diet? a lot of americans don't. I see a lot of carts in front of me at the grocery store with junk only in them, but there are also a lot with mostly healthy foods.
Haven't almost 1Bn people intermittently fasted during Ramadan for centuries?
Shouldn't there be enough evidence to get an idea if there's possibly a correlation?
There have been recent studies on the impact of fasting during pregnancy. Here's two:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377932/ > A total of 215 women were included in the study, 123 women fasted, and 92 women did not fast. Only 2.8% of women knew that fasting is forbidden in pregnancy. Sixty five percent of women reported weakness as the main reason for not fasting. The rate of gestational diabetes, pregnancy induced hypertension and preterm delivery was higher among women who fasted (17% vs 14%, 7% vs 2%, 9% vs 9%) respectively, compared to non-fasting women, but were not found statistically significant. There was no difference in anthropometric measurements of newborn, among both groups.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931121/ > Fasting during pregnancy was associated with reduced birthweight, in particular for fasting during the first trimester (-352ˑ92g, 95% CI: -537ˑ38; -168ˑ46). Neither dietary composition nor altered sleep were directly associated with birthweight. However, dietary composition during Ramadan outside of fasting hours seems to moderate the fasting-birthweight association, which disappeared for women switching to high-fat diets.
The benefits can be negated by what you eat outside the fasting window. Anecdotally, a few guys I knew feasted on baclava and super sweet tea first chance they got. also not drinking any water during the fast, especially in hot climates might be net unhealthy independent of any fasting benefits. I don't know any studies on that though, happy to stand corrected...
They also abstain from drinking water.
Medical science has clearly shown that this is bad for your kidneys. Possibly catastrophically bad.
Who should I believe, science or medieval superstitions?
Then religious muslims around the world, who all fast every year, must have the highest rate of medical issues related to their kidneys. Is there any such studies showing this?
Any studies done on potential health effects due to Ramadan will need to deal with the issue of noncompliance, i.e. to what degree do people observing Ramadan actually stick to the fast and not “cheat” at all. But I can imagine that due to the religious significance of the fast, you likely won’t get accurate self-reports of noncompliance. It would also be hard to conduct an accurate observational study since the subjects’ behavior will change due to being observed, again, because of the religious aspects. Without good noncompliance data, I’d be skeptical of any firm conclusions.
If there isn't any evidence to back it up, then it's just an assumption.
Should be compensated by the lack of alcohol intake
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>>Haven't almost 1Bn people intermittently fasted during Ramadan for centuries?
As a Muslim, I can tell you we tend to over eat, generally after we break our fast. It kind of defeats the whole point of fasting. In most cases its unavoidable as breaking fast is a social event for most people.
Im guessing before food got abundant the results would be quite different, but again back then most of the world had little to eat any way.
The goals of fasting during Ramadan are not to train people for intermittent fasting. Its because the religion/god said so, and to some extent make you feel how the poor feel as thats how life works for them everyday.
There is also a thing about fasting every Monday and Thursday which pious people tend to do often. But in general I have seen only good things happen to people who eat less. Muslims or not.
Are you reading that right?
> The investigators were comparing median survival between the CR and control (CON) groups, not longevity or lifespan per se.
As I read that, it wasn’t that the study showed that caloric restriction didn’t extent lifespan. It’s that they weren’t investigating the effect of caloric restriction on lifespan, so no conclusions can be made from the study.
No, read the article I posted.
TL;DR: there are 2 monkey studies, with unclear/conflicting results, both had pretty shitty diets, the calorie restrictions were severe, the benefits minimal at best.
The quote I provided was from the article. I’ve read the whole thing and I’m still parsing it (and your statement about both being fed shitty diets) as going against your original assertion: “Studies of caloric restriction in monkeys didn’t cause lifespan extension, casting doubt on its effect in humans.”
According to Attia, the studies weren’t specifically studying life extension, and all the diets were non-typical for the monkeys being studied. So, to me, this argues not that caloric restriction doesn’t cause lifespan extension in monkeys, but that we cannot know from these studies whether caloric restriction with a healthy diet causes lifespan extension in monkeys, which is what we really want to know. I wouldn’t expect to extend lifespan by eating hamburgers and fries but less of them, and that seems analogous to what the studies did.
To me, this simply leaves the question of caloric restriction in humans unanswered instead of casting doubt on it. Big difference.
Hamburgers aren't necessarily unhealthy. Plain ground beef is an excellent nutrient source. It depends what else you put on them.
Mmmmmmm mouse bread
I read it more like a mouse sandwich.
I don’t think there’s much meat on a mouse though, especially when the experiment is to have them eat less.
No, the GP is referring to breaded mice. Indeed, the recipe is so easy. Dip mice in batter and deep fry.
Wait, isn't Attia a big advocate of periodic fasting?
Not anymore. More recent research has failed to find any real benefits to intermittent fasting, at least for people who are already at a healthy weight. And it seems to have some negative effects for body composition.
https://peterattiamd.com/ep-300-exercise-nutrition-fasting-m...
Note I used periodic instead of intermittent for a reason. I seem to recall he was recently for something like a day a day and a half fast per month. Don't follow him that closely, did he move away from that too?
I think he no longer fasts, 1. because it reduces muscles 2. because of lifestyle changes; he now spends almost all time with the family.
>>he now spends almost all time with the family.
I see this too, for some reason people who don't fast kind of find it rude if people around them are fasting. Families even more so.
It's generally uncomfortable to share meals with people who aren't eating. It's deeply ingrained in many cultures to "break bread" in a way, so I think that's why it can be perceived as rude.
and thrown out with the bathwater is we've bred these mice to be very similar to us in some cases. if you wanted these studies done on humans you'd be dead before the results came back positive or negative.
Interesting question is why it didn't work for monkeys. It might have been a difference in protocol.
Studies on monkey's are not easy to repeat. Somebody should test caloric restrictions on mice with explicit goal of making it not work.
Why? It's much more likely caloric restriction extends the lifespan of mice and doesn't similarly extend the lifespan of primates.
What does making some bad scientific study that tells you something incorrect about mice help?
> that tells you something incorrect
I know I’m just nitpicking here but I believe you mean “inconclusive”. If we knew the findings specifically to be incorrect then we’d be learning something.
I'm not advocating a bad scientific study. I'm advocating a good one for detecting what might be another cause of it not working for monkeys other than 'duh! monkeys aren't mice!"
It's not about finding something inconclusive or incorrect. It's about finding all the ways you can make caloric restriction not cause extended lifespan in mice without harming them in some obvious ways that are hard to apply accidentally in research setting.
For example, maybe caloric restriction doesn't work if you feed mice badly inappropriate diet.
Just speculating. Maybe different levels of stress. Mice feel comfortable and happy in small places. Chimps not so much.
Chimps are also very muscular animals. Less fat to burn.
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I can't see a clear conclusion, unfortunately. 'Further study required' as ever. It also seems that 'resilience' to the stress of caloric restriction is key to gaining most benefit but it's not clear exactly what resilience is, and whether it's manipulable.
From the article:
Weight loss and metabolic improvements do not explain the longevity benefits of severe dietary restrictions.
Cutting calories by 40% yielded the longest longevity bump, but intermittent fasting and less severe calorie restriction also increased average lifespan. The dieting mice also displayed favourable metabolic changes, such as reductions in body fat and blood sugar levels.
However, the effects of dietary restriction on metabolism and lifespan didn’t always change in lockstep. To the authors’ surprise, the mice that lost the most weight on a calorie-limited diet tended to die younger than did animals that lost relatively modest amounts.
This suggests that processes beyond simple metabolic regulation drive how the body responds to limited-calorie regimes. What mattered most for lengthening lifespan were traits related to immune health and red-blood-cell function. Also key was overall resilience [...] The most-resilient animals lost the least weight, maintained immune function and lived longer.
In one of the most comprehensive clinical trials of a low-calorie diet in healthy, non-obese individuals, researchers found that the intervention helped to dial down metabolic rates — a short-term effect thought to signal longer-term benefits for lifespan.
But the mouse data from Churchill’s team suggest that metabolic measurements might reflect ‘healthspan’ — the period of life spent free from chronic disease and disability — but that other metrics are needed to say whether such ‘anti-ageing’ strategies can truly extend life.
Mice are very different from humans in that they are prey and we are predator. The reason that this is significant is that evolutionary, mice life history is optimalized for more offspring and shorter life, whereas predators are optimized for long life and few offspring. We know since 1993 with the discovery of the daf-2 gene (a nematode insulin receptor) that genetics can drastically affect longevity. However, and this is my own professional hypothesis, in humans we have tuned the genetic dial to max lifespan, whereas in mice and worms it is not. In these animals there is plenty of flexibility left to tune up lifespan, not so in humans. We may see moderate effects due to increased health though.
Please can you tell me more about the daf-2 gene and it's role in lifespan for nematodes? Any explainers on this? How does insulin relate to it - the metabolic aspect?
I can point you to the abstract of my PhD: https://biblio.ugent.be/publication/3075889. Mutations in the daf-2 gene tend to result in huge shifts in physiological and metabolic makeup. The challenge is discriminating those changes that are relevant for longevity from those that are not.
This is super interesting. Where are you planning on taking/applying this?
> We know since 1993 with the discovery of the daf-2 gene (a nematode insulin receptor) that genetics can drastically affect longevity.
We've known that since we observed that humans can easily live more than 70 years while cats tend not to go past 20. And presumably well before then.
IMHO, it is all about lowering oxidative stress. Eating creates oxidative stress in the body because to eat means to create ATP and that means electrons are increased in the mitochondria. More electrons = more oxidative stress in the form of superoxides.
I will say that Calorie Restriction with Optimal Nutrition (or CRON) is the healthiest diet but should be geared towards ones heritage or genetics (which is why I think all of the studies on humans have such variable and confounding outcomes.).
That doesn't seem plausible. Hard exercise increases oxidative stress and yet we have pretty good evidence that frequent hard exercise is correlated with longer lifespan.
Calorie restriction like the nonsense you're promoting would leave me too weak to do my favorite activities.
You’d be surprised… weight lifting while intermittent fasting is quite effective
Effective for what?
Losing muscle
Bodybuilders were the first people to start intermittent fasting after the mouse study. The title of the front page of https://leangains.com/ is "Leangains - Birthplace of Intermittent Fasting"
April 14, 2010: https://leangains.com/the-leangains-guide/
> we have pretty good evidence that frequent hard exercise is correlated with longer lifespan.
Like bodybuilding?
More like resistance training than bodybuilding (bodybuilding is more about aesthetics than strength, although there is a significant linkage). Falls are a leading cause of death and disability in the elderly. Old people who fall and break a hip seldom fully recover, lose mobility, and are often dead within a couple years. Being strong enough to stabilize your joints and catch yourself before hitting the ground is extremely important (although this is difficult to study through randomized controlled trials).
https://peterattiamd.com/avoiding-injury-part-i-eccentric-st...
By the way, this is one reason why mouse studies on longevity don't translate well to humans. Lab animals live in safe, flat cages where there's little risk of musculoskeletal injuries. The real world where humans live is far more hazardous.
Exercise reduces weight. Extra weight is just past eating we carry on our body to eat later.
We are slowly learning that our immune system is the key to longevity.
Many articles these last few years on ways to renew it, ways to treat dysfunction, and the common bad guys we really need to remove from our bodies as they are directly linked to currently incurable diseases like T1D, MS, Alzheimer’s, Parkinson’s, ME/CFS, Long COVID, and more.
It seems very realistic we may cure/reverse disease course for a handful of these within the next decade at this rate. Many novel clinical trials are happening to probe at the causes and if proven, we could have new drugs quickly due to the pandemic forcing supply chains to be able to meet antigen targets.
> the common bad guys we really need to remove from our bodies
Can you elaborate?
Over the last four years we have made tremendous progress in identifying pathogenic antigens as the main culprit in these diseases. Some may be caused by undetected low grade chronic infections and some may be lingering antigens causing constant immune system activation / dysfunction.
But what controls the immune system?
IMO it is oxidative imbalance that dis-regulates the immune system, leading to a hyper or hypo inflammatory state. That is, autoimmunity or immunodeficiency.
It's more nuanced than that.
genetic predisposition (immune/HLA genes working or not), infections (potential for antigen persistence), diet, environmental factors, stress, etc all also contribute heavily.
can you elaborate what are the medical trials which are going on for this?
https://www.nature.com/articles/s41392-024-01911-3
https://www.nature.com/articles/s41531-024-00716-z
https://www.nature.com/articles/d41586-024-00470-5
https://www.science.org/content/article/long-covid-trials-ai...
https://videocast.nih.gov/watch=54970
https://www.nature.com/articles/d41586-024-00871-6
https://www.nature.com/articles/d41586-024-01274-3
https://www.fda.gov/drugs/news-events-human-drugs/fda-approv...
Immunotherapy is entering the golden age and we're about to find out what and what doesn't work.
I’m skeptical it has basis in medicine, but I’m here to see too.
If you do intermittent fasting you won't necessarily live longer, but it will feel much longer.
Thank you for this, the only result that does not need more studies to be proven.
I laughed at this
Only initially. After a while, hunger and craving feel less of an emergency, and blends into the background, like breathing is--you tend to notice it's happening occasionally, but then go meh.
I believe that's the secret effectiveness of intermittent fasting. It teaches people who have a panic response when they feel the faintest bit of hunger how to wait, and over a long period of time kills that panic response.
I started IF probably around 2014 at 215 lbs (6'), and dropped about a pound a week for 6 months of it, leaving me at probably 185. Over the next year, I went back up to maybe 205, then did another six months and got down to 180. This happened probably twice more, and by 2020 my weight had reset to 170-175.
By reset, I mean that since 2020, I've paid absolutely no attention to my weight, or the amount I eat (although the variety is important.) I'm always between 169-176. At this second, I am 171.4 lbs. I think intermittent fasting taught me to be that way. Learning that you're not going to die if you don't eat for the rest of the day is like learning a language. It's recalibrating your own instinct for homeostasis, which is the characteristic intrinsic urge that all living beings have. It resists tampering, and really has to be convinced over time.
Caloric restriction (CR) leading to longer lifespan doesn’t generalize, including rhesus monkeys [1]. Moreover, across various species there seems to be negative correlation between average lifespan and effectiveness of CR and lifespan extension [2]. [1] https://x.com/cremieuxrecueil/status/1844282914521096501 [2] https://x.com/powerfultakes/status/1844310815819931661
Crémieux is fantastic, highly recommended.
Every single longevity (life extension) supplement or drug or technique that I've ever looked at involves pushing the person DOWN to a baseline
Which means even if they work to give you more years, you will lose fitness.
It is physically impossible to be held down to baseline and yet achieve stress-adaptation from exercise.
Everything from NAD+ supplementation to metformin to fasting, they all push your metabolism and other bodily function to an idle state.
It is useless, you'll live longer but you will be feeble.
Yes, there is a balance. IF you think of your body like a car it can make sense. The more you drive your car the faster it will wear down. Not driving your car can help it last a long time but it is useless. But driving it to much and too fast will wear it down before its' time.
Drive your car when you need to, but not too fast. And make sure you give it good gas and take care of the fluids and maintenance. And live knowing that everything is impermanent and one day your car will be gone.
Thank you for continuing the long tradition of using car analogies to explain things on message boards. This is a pretty good one.
i thought about this also but then there is this recent science that the body of a office worker uses the same calories as someone doing body work. saw it on kurzgesagt. so by this theory humans should be very energetic even with only the baseline
I only burn 80 calories when running a 7 minute mile but the average person uses a lot more if they are untrained.
The office-worker uses the same calories as a workout because they have no fitness and their heartrate is sky high even at idle.
Is heart rate directly proportional to calories burned?
Some studies on humans suggest that ‘moderate obesity’ can reduce lifespan by about 3 years [1]
I’m curious if there are any specific studies comparing the longevity of individuals with a BMI lower than 20 versus those with a BMI closer to 30.
[1] https://www.ox.ac.uk/news/2009-03-18-moderate-obesity-takes-...
Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis
https://pubmed.ncbi.nlm.nih.gov/23280227/
"Relative to normal weight, both obesity (all grades) and grades 2 and 3 obesity were associated with significantly higher all-cause mortality. Grade 1 obesity overall was not associated with higher mortality, and overweight was associated with significantly lower all-cause mortality."
Overweight: BMI from 25 - 29.9.
How Much Should We Weigh for a Long and Healthy Life Span? The Need to Reconcile Caloric Restriction versus Longevity with Body Mass Index versus Mortality Data
The money shot: "...But other factors — including immune health, genetics and physiological indicators of resiliency — seem to better explain the link between cutting calories and increased lifespan..."
Anecdotally, every chronically sick person (always getting colds, coughs, sinus infections, headaches, UTIs, other symptoms) I know is overweight. This doesn't show causation, maybe having a weak immune system contributes to being hungry and overeating but all the normal weight or lean people I know seem to rarely be sick.
Knowing nothing about your surroundings, overweight people tend to avoid medical care if they can bare with the symptoms, which make them more subject to longer colds, infections, headaches etc.
It's a well known effect: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381543/
I wonder if the same is/was true for smokers? I can imagine people not wanting to hear "you need to lose weight" every time they visit the doctor. What about "you need to stop smoking" or "you need to stop drinking" or admonishments to stop any other self-destructive behaviors?
Yes, there's probably a similar effect, with a key difference being that smoking and drinking can be masked a bit easier if it's not an emergency (e.g. sobering for a day before going in) where there's no lying about one's weight.
That doesn't make any sense. Medical care can't really reduce the length of common cold symptoms. It mostly comes down to the effectiveness of your own immune system. Obesity has a number of negative effects on the immune system.
Would you disagree that modern medical care can help improve the effectiveness of your immune system ?
Or even that we have the means to reduce the symptoms ?
Or protect your immune system from additional threats while it's focusing on a virus for instance ?
Yes, I would disagree with that. Unless someone has a treatable medical condition such as HIV infection, modern medical care can't improve the effectiveness of your immune system. It's mainly down to lifestyle and age.
There's no cure for the common cold. Some OTC remedies can slightly reduce symptom severity but they're nearly useless. Zinc supplements might marginally reduce duration of symptoms for some patients.
Frequent hard exercise, sunlight exposure, and limiting body fat content are far more effective interventions for immune system function than anything a physician can give you.
there are new reportsin humans that intermittent fasting doubles your rate of heart disease. I am curious to know if it decreases mortality at same time.
https://newsroom.heart.org/news/8-hour-time-restricted-eatin...
I think that what is important is to give time for your body everyday to recover from the food intake (which can be an inflammatory insult) and give it time to repair. Maybe some people may reach ketosis in 8h, which is an injury itself. It is like the need to sleep and the need to rest after exercise or the need for vacation after long work days. Every insult needs to be compensated for and repaired.
Also the idea of having to eat 3 meals a day, does not exist in nature or in our past history. This developed with industrilization when hard working men needed energy at work. But it is clear that evolution never needed to limit excessive food intake. It mainly dealt with famines and low food intake. We never aquired the necessary breaks to stop eating. we need to keep this in our thoughts daily to actively stop ourselves from eating till our death
I'm doing 24h breaks between 24h eating periods because I was slightly overweight. I lost 10lbs in less than 2 months without any additional restrictions or exercise. I noticed no side effects. It's also super easy to keep up esp. when compared with my previous attempt at restricting sugary snacks. 'When' is so much easier to manage than 'what'. If I feel hungry I just need to distract myself for few hours and it's fine.
Try weight loss tea instead. Will affect your sleep a bit, but you can eat normally.
Wait, so you're just not eating every other day?
One day I'm eating only till 4PM and the other only after 4PM. And so on ... So the breaks are often a bit longer than 24h because I rarely have my last meal right before 4PM. But not as long as if I was eating every other day. Because then it would be two nights and one day between the periods of eating and I think that could be a bit much for me.
Absolutely fine thing to do IMO. Takes a tiny amount of resilience but works great.
Anorexia works!
Wow. Losing weight by not eating apparently is not the correct, moral way to do it either. That's a kind of shaming that even Ozempic patients don't get. Apparently the only moral way is to struggle with terrible exertion and discomfort and mostly fail but sometimes succeed. Only then you earned joining the club of people with healthy, normal weight.
Anorexia is when people starve themselves to an unhealthy degree based on mental issues, body dysmorphia, something like that. Someone intermittent fasting to lose excess weight and having success at it isn't the same.
The trouble is who do you ask? Because naturally people with eating disorders won't think, or say, they have an ED. They'll say they're living a healthier lifestyle and they're getting all the food they need.
I see this all the time with body builders. They're convinced they're healthy, but in reality, they absolutely despise food. It's a chore to them. And to top it off they have extreme body dysmorphia, often pushing them to drug use that kills them.
This is probably the dumbest comment I've seen on HN regarding weight loss so far, and that's really saying something considering the recent Ozempic thread.
Does the study show why (as the title says)? Can’t say I got it…
Nope. The 'why' in the title is misleading. They suspect some unknown factors but aren't sure what and whether they can be targeted for anti-ageing interventions.
Could be the reason is aging is programmed and when food is scarce the program changes to delay aging, such that the organism has a better chance to survive longer and reproduce once food is less scarce and at that point turn up the rate of aging again.
That is almost how Hoeijmakers explains it, but not quite, see the link in my other comment for pointers.
He thinks aging is not programmed per se, but what is programmed is the switch of modes. Aging happens automatically as faults built up in dna over time. If an organism switches from "organism growth mode" to "repair dna mode", the chance of survival increases.
Now, how to conveniently trick the body into the latter mode is the million dollar question.
Or that extra foods puts more stress on your organs. Liver, kidneys, pancrease, etc have to do more work and for some reason the body isn't able to repair that and they wear out quicker.
All tissue in organs are under stress and cells die of. That is normal, also for young people. The body produces new cell by making copies of dna.
What is problematic however is that after some time, there is a built up of errors in the dna. If those errors do not get corrected, that is when you see a decline in organ quality, what we call aging.
If interested, see my other posts for more pointers.
Some googling suggests this is what causes type 2 diabetes. Pancreas wears out and stops producing insulin.
After chronic insulin resistance causes higher amounts of insulin to be generated for long periods of time
And that's why you shouldn't rely on Google for anything important. Type-2 diabetes has more to do with insulin resistance than lack of insulin production.
There is just one “little” problem which remains unsolved: how to make money while “not selling” calories? It’s easy to make money by selling more calories: you add sugars, artificial compounds leading to mental addiction, you invest in heavy marketing and expansive distribution channels. All of this makes your product available and desirable, a money printing machine, at the cost of society’s health and wellbeing. So until someone can answer the question of how to do the same without the side effect to society, unfortunately the majority will continue to suffer for the benefit of the very few.
There is no particular need for society to have an industry that sells unhealthy food. It can go the way of horses, would only be a net positive for society.
The old adage here applies:
"How do you sell ice to Eskimos?
You call it French ice."
Same kinda thing.
You call the net-negative calories: French calories or some other crap like that.
Who is 'you'?
You is the processed food industry.
Its a way for us to winnow out the weak willed
It would be just as true but much funnier if you said "sinners".
Sorry, but this is such a bad conspiracy, like flat earth level. You could look at history, at communist countries where there were not evil capitalist with evil ads and people still were eating 3 or more times a day and eating meat, eggs and other calories.
Or you are aware of some tribe that eats one every week and lives 150+ years or something like that ?
A TV documentary in 2002 said they studied 2 groups of rats. The control group had a steady supply of food and could eat whenever they want. The other group was on a diet.
After 2 years, the control group all sat in a corner of their cage being fat and lazy. The other group continued powering their ferris wheel generators and were not being lazy at all.
They hypothesized that too much food made the body more prone to free radicals and the damage was more difficult to repair in the control group. Effectively making them age faster than the diet group.
Not sure a TV documentary from 22 years ago is the source to get scientific explanations from ...
TV documentaries today are arguably worse. Dumbed down to "here's someone who knows science stuff" and "here's a startup that does science stuff" over and over again.
The point I was trying to make is that many "news" articles aren't really new. It's not unheard of that the publisher just wants your attention so they'll keep rehasing old stuff.
I'm pretty sure the free radical theory of aging is not mainstream any more. Too many studies of antioxidants have shown that they don't help, out even make things worse
Reminds me of the rat park experiment on drug addiction. Put the rats in small cages and give them morphine, they get addicted. Put them in the rat park where they have lots of things to do and they don’t get addicted. Food overindulgence is probably result of similar effects too.
This longer life experiment probably has issues too. Like the rats might be getting fed some crappy food in a cage where they can’t do anything and so just sit there and get fat. As opposed to getting not enough food and go into some kind of hibernation stage where they don’t do anything and just sit there and not get fat. What a life for either of these rats. What a life for a human to emulate.
The study itself is here:
https://www.nature.com/articles/s41586-024-08026-3
It adds this interesting point:
Our findings indicate that improving health and extending lifespan are not synonymous and raise questions about which end points are the most relevant for evaluating aging interventions in preclinical models and clinical trials.
> Weight loss and metabolic improvements do not explain the longevity benefits of severe dietary restrictions.
The overlooked word is "Severe".
These studies either restrict a lot of calories (40% for one study in the article), or are fasting for long periods of time for the animal; Mice start dying without food after 2 days - you aren't going to see the same effect in humans by skipping breakfast.
There is an interview [0] with Hoeijmakers, who has championed the idea that the single root cause for both aging and cancer are faults in dna. Faults in dna prevent rna copies, aka _transcription stress_. One of his theses was that if faults in dna happen randomly, we would see aging the most in the largest genes. [1]
In his experiments [2] he was able to turn the knob of dna repair, also in humans, from "organism growth" to "organism survival".
Survival mode can be induced when confronted with food scarcity. If we can unravel the underlying mechanism, we should be able to enlarge our lifespan.
___
0. https://www.nrc.nl/nieuws/2024/10/11/de-geneticus-die-gezond...
1. https://www.cell.com/action/showPdf?pii=S0168-9525%2824%2900...
There was a Veritasium video about these two modes. Survival mode is triggered not just by food scarcity, but also by extreme heat, extreme cold, and one other thing (I forgot).
The single greatest contributor to DNA damage is oxidative stress.
For example: https://www.mdpi.com/1422-0067/23/19/11664
Hoeijmakers mentions that. Fasting activates anti-oxidants.
For example, in the Netherlands hospitals are starting to experiment with fasting before a surgery. During surgery arteries arteries are opened, bringing blood in contact with oxygen. With pre activated anti-oxidants damage will be minimized, helping with recovery.
I've been following this research for two decades. In my opinion, the most plausible explanation for the genesis of these life-extending adaptations is the methionine and branch chain amino acid restriction that is incidental to calorie restriction (that would be only cyclical in humans).
The title is misleading. This is not true in more complex animals like humans.
> "The intervention is a stressor,” Churchill explains. The most-resilient animals lost the least weight, maintained immune function and lived longer.
Very happy to hear that my struggles with weight loss are because of my resilience and a strong indicator that I will live a long life ;)
I love how neither this Nature article nor the actual study shed any new light on this area. We've known about this for decades; we've also known that it isn't just down to metabolic rate changes for... decades.
This week I actually did a 48 hour fast and then two 24 hour fasts. I ate between all of them, and a lot before. I personally find that hunger comes in waves. If you wait out the first wave, it doesn't continue to build. It will leave and then return, like someone interested in you at a bar.
It makes me think that our 3 meals a day culture responds to those initial waves of hunger, and likely leaves of eating more than we need to. Would make sense that there's an overall toll from that on lifespan.
I do 1.5 meals a deal, but I 100% agree, overeating is really terrible for overall lifespan.
How much time between the 48 and 24's? With fasts like that, does the food you eat on resumption matter?
I did one meal in between. I just make sure to eat a balanced meal (fruit and vegetables, proteins, some healthy carbs, healthy fats).
I'm thinking of moving to OMAD (one meal a day). I love eating big meals, and I find it helps my focus to not be thinking about eating during the day. Only challenge is not eating post workout
I really just read that headline as “eating mice leads to a longer life” I’m going back to bed
My husband had PD-5 programme about 4 months ago. he sleeps soundly, works out frequently, and is now very active. It doesn’t make the Parkinson’s go away but it did give him better quality of life. I’m surprised a lot of PWP haven’t heard of it, we got the treatment from binehealthcenter. com
Between this and generally trying to lose weight I've been attempting to eat less, but I also find that it tends to make me lethargic and inclined to go to bed earlier. I hope I can find a middle ground between reducing calories but still being able to do as much as I want to in a day.
I'm someone who is naturally fat. I have spent my whole life trying to lose weight. Many of you here have excluded fat people from your lives so you won't hear this from someone else: you are the weight you are due to factors outside of your control. You can slightly change your weight temporarily but your body will always reset or give you stress signals to reset it yourself. I know, I have starved myself, done incremental weight loss, worked out almost year round as a football player, it doesn't stay off and it barely comes off (10-20 pounds total is insignificant). Fat people shouldn't have to starve themselves to meet societal standards and personally I won't.
PS. The reason fat people don't like going to the doctor is because they quite literally will not treat us for our issues in most cases. I've been trying to get treatment for my crippling back pain for years and have been told by physical therapists not to do physical therapy until I'm on pain medication but even with this info doctors just tell me to exercise. I'd love to, in fact I'd love to take walks often but I physically cant.
Is it really starving yourself if you're simply given the goal of eating your recommended calorific intake for your height/sex?
You wouldn't be starving yourself. You'd just not be overeating.
But do not stop eating. My advice.
The human body knows how to cope with food scarcity: that's what it's used to since we appeared as a species on Earth. But it does not know how to cope with the abundance of food and energy.
Didn't we start living longer as we had access to more and better food...and ate it?
We did. But we have overshot a bit.
You are thinking of Antibiotics.
No I'm not...
Let me rephrase that less sarcastically.
More food did not lead to longer lifespan in modern humans. Antibiotics are responsible for increasing human lifespan and estimated 20 years.
https://www.antibioticresearch.org.uk/happen-antibiotics-sto...
I suspect they are taking about the time during which our ancestors evolved into modern humans.
I thought this research didn't reproduce with primates ?
I'm not a mouse.
Fasting is widespread in religions. Can’t be a coïncidence.
It's more likely because hunger was a common human experience for entire history so doing it on purpose seems like a quirky, hip thing to do and that's what religions flock to for the purposes of attracting followers.
I think religious fasting is more about the symbolic significance of fasting as an act of self denial and self cleansing, but there are plenty of religious dietary restrictions in religions that probably stem from ideas about health and food safety.
I think the ideas get stretched. But fasting is kind of used as a means to avoid gluttony.
Fasting does keep you little alert and productive, compared to people who aren't doing it.
Stay Hungry, Stay foolish. [Have enough enough appetite to learn more, and be naive enough to try doing hard things]
Fasting gets you high. Bundles well with meditation, sleep-deprivation, etc.
(which leads to "religious visions" etc)
So is wearing funny hats, and performing acts of violence on opposing believers and unbelievers (not to mention their own believers).
I wouldn't put too much "faith" in religions authority on whats correct or not.
Also, absolutely it can be a coincidance. Your standards for truth are very poor.
I am currently seeking funding for my research into the longevity effects of wearing funny hats. Previous research on organ-grinder monkeys has been ambiguous and it's hard to get IRB approval. My lab is currently developing tiny hats for fruit flies and investigating what a fruit fly finds funny.
Gnawing on wood is good for your teeth, study in mice shows why.
[dead]
Refuted by every Jewish grandmother ever.