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.
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.
> 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.
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.
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.
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.).
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.
IMO it is oxidative imbalance that dis-regulates the immune system, leading to a hyper or hypo inflammatory state. That is, autoimmunity or immunodeficiency.
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.
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..."
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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).
[+] [-] tomp|1 year ago|reply
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...
[+] [-] throw8932899|1 year ago|reply
Humans (and other non-tropic animals like mice) have adaptation for seasonal food availability, and can go through extended fasting.
[+] [-] vlovich123|1 year ago|reply
[+] [-] onlyrealcuzzo|1 year ago|reply
Shouldn't there be enough evidence to get an idea if there's possibly a correlation?
[+] [-] dimal|1 year ago|reply
> 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.
[+] [-] 8b16380d|1 year ago|reply
[+] [-] unknown|1 year ago|reply
[deleted]
[+] [-] aulin|1 year ago|reply
[+] [-] unknown|1 year ago|reply
[deleted]
[+] [-] ineedaj0b|1 year ago|reply
[+] [-] scotty79|1 year ago|reply
Studies on monkey's are not easy to repeat. Somebody should test caloric restrictions on mice with explicit goal of making it not work.
[+] [-] aaron695|1 year ago|reply
[deleted]
[+] [-] austinjp|1 year ago|reply
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.
[+] [-] CraftingLinks|1 year ago|reply
[+] [-] FollowingTheDao|1 year ago|reply
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.).
http://optimal.org/voss/cron_overview.html
[+] [-] thenerdhead|1 year ago|reply
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.
[+] [-] voisin|1 year ago|reply
Can you elaborate?
[+] [-] FollowingTheDao|1 year ago|reply
IMO it is oxidative imbalance that dis-regulates the immune system, leading to a hyper or hypo inflammatory state. That is, autoimmunity or immunodeficiency.
[+] [-] aashu_dwivedi|1 year ago|reply
[+] [-] jebarker|1 year ago|reply
[+] [-] KolmogorovComp|1 year ago|reply
[+] [-] aherforth|1 year ago|reply
[+] [-] penguin_booze|1 year ago|reply
[+] [-] sukhavati|1 year ago|reply
[+] [-] MrBuddyCasino|1 year ago|reply
[+] [-] ck2|1 year ago|reply
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.
[+] [-] tlogan|1 year ago|reply
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-...
[+] [-] belter|1 year ago|reply
[+] [-] scotty79|1 year ago|reply
[+] [-] mikesabbagh|1 year ago|reply
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
[+] [-] bjornsing|1 year ago|reply
[+] [-] austinjp|1 year ago|reply
[+] [-] macrolime|1 year ago|reply
[+] [-] exceptione|1 year ago|reply
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.
[+] [-] 0x1ceb00da|1 year ago|reply
[+] [-] elwebmaster|1 year ago|reply
[+] [-] kelipso|1 year ago|reply
[+] [-] Balgair|1 year ago|reply
"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.
[+] [-] wildrhythms|1 year ago|reply
[+] [-] apwell23|1 year ago|reply
[+] [-] bubblesnort|1 year ago|reply
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.
[+] [-] Plankaluel|1 year ago|reply
[+] [-] amanaplanacanal|1 year ago|reply
[+] [-] kelipso|1 year ago|reply
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.
[+] [-] utopicwork|1 year ago|reply
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.
[+] [-] exceptione|1 year ago|reply
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...
2. https://www.nature.com/articles/nature19329
[+] [-] mmooss|1 year ago|reply
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.
[+] [-] rKarpinski|1 year ago|reply
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.
[+] [-] mrangle|1 year ago|reply
[+] [-] komali2|1 year ago|reply
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 ;)