Eating less can lead to a longer life: study in mice shows why
nature.com
nature.com
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...
I don’t think there’s much meat on a mouse though, especially when the experiment is to have them eat less.
Studies on monkey's are not easy to repeat. Somebody should test caloric restrictions on mice with explicit goal of making it not work.
What does making some bad scientific study that tells you something incorrect about mice help?
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.
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.
Chimps are also very muscular animals. Less fat to burn.
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.
> 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.
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.
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.
https://peterattiamd.com/ep-300-exercise-nutrition-fasting-m...
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.
Humans (and other non-tropic animals like mice) have adaptation for seasonal food availability, and can go through extended fasting.
You just ignored the context of ketogenic metabolism being more similar in humans and mice than humans and chimpanzees.
~ George Box
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.
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!)
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...
NuSI funded two trials that could test the energy balance hypothesis. (This is an important point: these experiments tested the null hypothesis, which was energy balance, although the experimental tests were based on predictions made by the carb insulin model.) One trial, led by Kevin Hall and Eric Ravussin, was a non-randomized pilot study that they interpreted as consistent with the energy balance hypothesis. That interpretation was challenged by David Ludwig who led the other trial, an RCT that Ludwig interpreted as inconsistent with the energy balance, calorie-is-a-calorie model. Hall et al challenged that interpretation.
If Peter changed his mind, which his book suggests he did, it could not have been based on the results from the NuSI-funded trials because their interpretations were contradictory, as experiments in science often are. Peter cares deeply about scientific method so I'm sure he understands this.
Holistically: https://pmc.ncbi.nlm.nih.gov/articles/PMC5563491/#S1
More pointedly:
> Five healthy rhesus monkeys, three male and two female, weighing from 2.4 to 6.1 kilos, were fasted for periods of 2 to 4 days... With one exception, the monkeys developed a ketosis within 2 days
https://www.sciencedirect.com/science/article/pii/S002192581...
Note that Attia's article is about rhesus monkeys.
Shouldn't there be enough evidence to get an idea if there's possibly a correlation?
Medical science has clearly shown that this is bad for your kidneys. Possibly catastrophically bad.
Who should I believe, science or medieval superstitions?
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.
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.
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.
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.
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.).
Calorie restriction like the nonsense you're promoting would leave me too weak to do my favorite activities.
April 14, 2010: https://leangains.com/the-leangains-guide/
Like bodybuilding?
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.
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.
Can you elaborate?
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.
IMO it is oxidative imbalance that dis-regulates the immune system, leading to a hyper or hypo inflammatory state. That is, autoimmunity or immunodeficiency.
genetic predisposition (immune/HLA genes working or not), infections (potential for antigen persistence), diet, environmental factors, stress, etc all also contribute heavily.
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.
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.
The office-worker uses the same calories as a workout because they have no fitness and their heartrate is sky high even at idle.
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.
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-...
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
It's a well known effect: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381543/
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 ?
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.
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.
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
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.
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.
"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.
Or you are aware of some tribe that eats one every week and lives 150+ years or something like that ?
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.
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.
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.
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.
You wouldn't be starving yourself. You'd just not be overeating.
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...
For example: https://www.mdpi.com/1422-0067/23/19/11664
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.
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.
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.
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 ;)
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.
How much time between the 48 and 24's? With fasts like that, does the food you eat on resumption matter?
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
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 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.
(which leads to "religious visions" etc)
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]