214 replies to this topic

[okok]

Right, i forgot about the wisconsin outcome, but still, accounting for that, it's a (weak) argument against CR.

[scottknl]

CR != malnutrition both in humans and NIA Monkeys by definition.

CR has 2 main rules: 1) get full nutrition 2) cut calories
If you're not getting rule #1 then you're not doing CR.

No, you are doing CR. You may not be doing CRON.

I don't think we know enough to be confident about what optimal nutrition, and therefore CRON, even is in humans, and probably not in monkeys. [...] Also, in numans, there is no such thing as CRON in children. Optimal nutrition in children requires more calories than they would get from CRON, otherwise they will have lifelong mental and physical deficits[...]

v, You are totally wrong. CR is not CR without adequate nutrition. Studies with animals in which dietary restriction of calories was attempted without ensuring vitamins, minerals and other essential nutrients like fatty acids, proteins etc. have always resulted in reduced lifespan and poor health. This is why McKay's work in 1935 was important.

CRON hasn't been applied in children because it stunts growth, not because it becomes malnutrition or because it produces defects. In animal studies the CR'd group grow up healthy and active, but smaller. Other cultures like the Laron syndrome people are otherwise healthy even if they have small stature, so lack of IGF-1 isn't a problem. You have no proof that it causes lifelong mental and physical deficits because it doesn't. Stunted growth is not a lifelong physical deficit and has nothing to do with mental ability. Or would you rather attack all short people as mental and physical cripples?
I thought not!

Stop spreading FUD about CR.

Edited by Michael, 19 September 2012 - 09:41 PM.

[TheKidInside]

I think the funniest thing here was the researchers were living in some alternative reality with their "calorie is a calorie" model. That to me is hysterically faulty and if you think you'll make it to even 60 in good health eating half a twinkie a day, well, godspeed as they say

great discussion so far, keep it up

[nhenderson]

On a personal note, I have been on intermittent fasting for sometime now (3xweek, @ ~900 calories). I just started a one day per week protein restriction ( < 20 grams), I have not had any blood work since starting this, but wow, I get really cranky and hungry on the those low protein days and I eat way more on the next day after the low protein day than I do on a "normal" ad libitum day.

[InquilineKea]

the NIA study showed that both controls and CR group lived similar lifespans. CR animals in no way lived shorter or less healthy lives compared to the controls. In fact both groups appear to have set a new record for mean lifespan of m. mulatta. Of course, there's still data to come, so the final result isn't in, but isn't likely to change significantly.

Really? How long do m. mulatta usually live? How long did they live in the Wisconsin study?

Edited by Michael, 19 September 2012 - 09:43 PM.

[scottknl]

what the NIA study showed was that both controls and CR group lived similar lifespans. ... In fact both groups appear to have set a new record for mean lifespan of m. mulatta. Of course, there's still data to come, so the final result isn't in, but isn't likely to change significantly.

Really? How long do m. mulatta usually live? How long did they live in the Wisconsin study?

I'm no expert, but http://animaldiversi...ca_mulatta.html

says

Range lifespan
Status: wild
30 (high) hours

Range lifespan
Status: captivity
30 (high) hours

Average lifespan
Status: captivity
36.0 years
[External Source: Max Planck Institute for Demographic Research]

Average lifespan
Sex: female
Status: captivity
23.0 years
[External Source: Max Planck Institute for Demographic Research]

Average lifespan
Status: captivity
35.0 years
[External Source: Max Planck Institute for Demographic Research]

Average lifespan
Status: captivity
26.0 years
[External Source: Max Planck Institute for Demographic Research]

Average lifespan
Status: wild
30.0 years
[External Source: Max Planck Institute for Demographic Research]

and I thought the original documentation for the study mentioned 27 years mean life expectancy. Maybe that's for the combined female and male populations. So 40 years+ is hitting one out of the park for the 4 CR and 1 control animals.

However, the Wisconsin study claims 27 years avg in captivity:
http://www.news.wisc.edu/16889

Rhesus monkeys, left to right, Canto, 27, on a restricted diet, and Owen, 29, a control subject on an unrestricted diet, are pictured at the Wisconsin National Primate Research Center. The two are among the oldest surviving subjects in a pioneering long-term study of the links between diet and aging in Rhesus macaque monkeys, which have an average life span of about 27 years in captivity.

So given that Canto and Owen average age of 28 are among the oldest of the Wisconsin cohort, they are relatively young at 32 years of age in 2012 assuming they get to 40 like the NIA study. So we have some time to wait before we know the answer.

FYI http://www.primate.w...wprc/press.html lists a lot of relevant studies.

I suggest that if the control animals in the NIA study are living to average age of 35, then they are significantly outliving the WNPRC study animals. (Many have already died). So the NIA controls were screwed up in some way by allowing them to "self regulate" their intake of food which seems to have resulted in CR in the controls group. Thus the finding of no difference between the groups.
cheers, KS

Edited by Michael, 19 September 2012 - 09:44 PM.

[nowayout]

v, You are totally wrong. CR is not CR without adequate nutrition. [..]

CRON hasn't been applied in children because it stunts growth, not because it becomes malnutrition or because it produces defects. In animal studies the CR'd group grow up healthy and active, but smaller. Other cultures like the Laron syndrome people are otherwise healthy even if they have small stature, so lack of IGF-1 isn't a problem. ...

You have no response, so you are injecting so many straw men into the thread I don't quite know where to begin.

Laron syndrome, growth hormone and IGF-1 related diseases, and short stature are irrelevant to CR, because they are not the result of CR. Short stature is not the same as the stunted growth you get from CR, so the mental or physical status of short people is irrelevant to CR. And good luck convincing people that what passes for the rudimentary intellect of calorie restricted mice has anything to do with people.

If you have anything besides invective to back up your claim that something that by your own admission stunts physical growth would not also stunt the developing brain (which after all is a physical organ requiring a proportionally huge amount of calories in humans compared to mice), in conflict with pretty much the whole of pediatrics, I'd be all ears.

Edited by Michael, 19 September 2012 - 09:47 PM.

[scottknl]

You have no response, so you are injecting so many straw men into the thread I don't quite know where to begin.

Laron syndrome, growth hormone and IGF-1 related diseases, and short stature are irrelevant to CR, because they are not the result of CR. Short stature is not the same as the stunted growth you get from CR, so the mental or physical status of short people is irrelevant to CR. And good luck convincing people that what passes for the rudimentary intellect of calorie restricted mice has anything to do with people.

If you have anything besides invective to back up your claim that something that by your own admission stunts physical growth would not also stunt the developing brain (which after all is a physical organ requiring a proportionally huge amount of calories in humans compared to mice), in conflict with pretty much the whole of pediatrics, I'd be all ears.

Properly implemented CR causes less production of IGF-1. This causes smaller size animals in studies of CR from weaning which translates to stunted growth in CR'd human children.

I challenge you to provide a reference in which there is any increase in deformed organs, or brain health which is directly due to CRON. Please don't provide any starvation studies as these are not CRON.

In terms of brain health on CRON you don't have far to look. The WNPRC study has produced a paper on brain health in the CR monkeys. Of course I can't prove to you that CRON works in children because no children have implemented CRON. It will have to remain an unanswered question if you won't accept the animal studies.

http://diabetes.diab.../61/5/1036.long directly talks about brain health in CR'd monkeys and shows brain images from both groups.

http://www.ncbi.nlm....les/PMC2877377/

Edited by scottknl, 08 September 2012 - 04:23 PM.

[Guest]

A lot has been written about the NIA-study and how it compares to the previously published results from the Wisconsin study - here as well as elsewhere in the bloggosphere and at the CR society maillingslist. However, I am still missing a conclusive summary about the startling results of the study. Apparently there are some information missing in the publications which would have to be enquired directly by the authors of the papers (the NCPR as well as the NIA ones).

So is anyone up to comprehensively evaluate the results of the two studies, why they have such diverging outcomes (or better interpretations thereof), the extend to which this can be attributed to CRON alone and the implications for CRON in humans?

[nhenderson]

I suggest that if the control animals in the NIA study are living to average age of 35, then they are significantly outliving the WNPRC study animals. (Many have already died). So the NIA controls were screwed up in some way by allowing them to "self regulate" their intake of food which seems to have resulted in CR in the controls group. Thus the finding of no difference between the groups.

The NIA controls were on restricted diets!

The funny thing about the reporting on the story that has been missed, but surfaced on the board here is that the controls in the NIA study were calorically reduced by 10% and both controls and the 30% restricted group seem to be living longer than other animals in captivity.

Edited by nhenderson, 11 September 2012 - 05:41 PM.

[pmcglothin]

Thanks to all for this valuable discussion of the monkey study. I have talked at length with several CR scientists about it. They and I agree that this study and the NIA study is nothing more than research on incarcerated animals. As I have noted in this blog post, such confinement would likely the genetic expression of these intelligent social primates.

But let's say for argument's sake that the horror of confinement did not exist in this study. Some of you have already pointed out the strange test results -- high glucose, triglycerides, T3, etc. This is a huge red flag -- likely meaning that the monkeys were following a diet that negated some or all of their CR benefits. That is easy to do, even when calorie are limited.

Paul

[AgeVivo]

Eh... sorry but with all due respect, that conclusion seems very biased and unscientific. And I wonder how scientific it is to turn the page so quickly.

Thanks to all for this valuable discussion of the monkey study. I have talked at length with several CR scientists about it. They and I agree that this study and the NIA study is nothing more than research on incarcerated animals.

1) The words in bold simply suggest a lack of arguments. The blog post doesn't bring much more.
2) then why did we wait for bad results to say so????? Would we have said the same thing if results were particularly good?? Certainly not.

As I have noted in this blog post, such confinement would likely the genetic expression of these intelligent social primates.

I think we need to digg much deeper. The NIA study was believed to be the reference. Rats and mice also need space.

Edited by AgeVivo, 15 September 2012 - 08:40 PM.

[AgeVivo]

Some of you have already pointed out the strange test results -- high glucose, triglycerides, T3, etc. This is a huge red flag -- likely meaning that the monkeys were following a diet that negated some or all of their CR benefits. That is easy to do, even when calorie are limited.

That is to me a good scientific approach. I think we need to dig further. Is it really *that* easy to explain such results? for example, can we reproduce analogous bad CR effects in rodents? I can't help but wonder if life extension by CR in confined rats hasn't been done in great conditions neither. So, would we reproduce the high glucose, triglyceride, T3 pattern in rodents under similar conditions? The help of the authors of the NIA study would be greatly needed to define the protocol because they know the details of their study.

Edited by AgeVivo, 15 September 2012 - 08:45 PM.

[Luminosity]

I've only seen a few fat people on TV but the ones I saw did look bloated, and inflamed and swollen.

Maybe you should adjust your set.

I actually came here to ask the administrators to delete my earlier postings because in retrospect I felt they were not very tactful, but you make that hard to do, Chupoman.

Your temperament isn't a great advertisement for whatever you are into.

Edited by Luminosity, 16 September 2012 - 05:01 AM.

[Chupo]

Maybe you should adjust your set.

I actually came here to ask the administrators to delete my earlier postings because in retrospect I felt they were not very tactful, but you make that hard to do, Chupoman.

Your temperament isn't a great advertisement for whatever you are into.

I'm glad I could at least make you realize how tactless they were. It's different when you can relate to the ones being disparaged, isn't it?

[pmcglothin]

'AgeVivo' wrote:

"Eh... sorry but with all due respect, that conclusion seems very biased and unscientific. And I wonder how scientific it is to turn the page so quickly."

Depends on the quality of the science. In this case, when the fallacious results can be checked for accuracy any day of the week by serious calorie restrictors their local lab, I think the page not only needs to be turned, it needs to be ended. Serious research on human calorie restriction have made this study an anachronism. Fact is that if you are following a CR Diet certain basic physiological things happen: Lower triglycerides, T3, glucose, etc. If that's not happening, something is wrong with your approach -- not CR itself.

Agevivo wrote

"2) then why did we wait for bad results to say so????? Would we have said the same thing if results were particularly good?? Certainly not."

Certainly yes! When the CR Society held its meeting at the University of Wisconsin, we were all aware that the monkeys, both the CR cohort and the controls, were on hunger strike. We thought then that the study was cruel incarceration. Throughout the history of the study, problems have surfaced with getting the monkeys to follow the protocol.

I appreciate your desire for serious scientific discourse, yet I do not think this particular study deserves it. The details, you wanted BTW of the study's protocol are provided in the attached paper sent to me by the NIA. As far as I can tell, tests conducted on the monkeys did not even look at the signaling pathways that human studies at Wash U. at UCSF (the CRONA research), and UCR (Spindler/Dhahbi) now consider essential.

Paul

Attached Files

•  Ingram et al 1990 DRInitiation paper.pdf   1.56MB   7 downloads

[scottknl]

One thing Paul didn't mention is the tendency for the female animals to live considerably shorter lives than the males. Perhaps this animal model for CR isn't really the best choice to investigate CR in humans. Maybe CR experiments are better suited to some other omnivorous animal with a long enough lifespan to see diseases of aging, Or perhaps Calorie Restriction followers could adopt a pet animal and record the animal's intake just as they would record their own. This would be much more humane than caging the animals for a lifetime.

[nowayout]

Fact is that if you are following a CR Diet certain basic physiological things happen: Lower triglycerides, T3, glucose, etc. If that's not happening, something is wrong with your approach...

But it did happen, in the adult-onset NIA monkeys. So if you are unhappy with the study, you would have to demonstrate in what way they early-onset monkeys' CR diet differed from that of the later-onset monkeys.

You would also have to explain why the group of adult-onset CR monkeys in the NIA study whose biomarkers improved did not live longer.

Edited by viveutvivas, 16 September 2012 - 02:00 PM.

[AgeVivo]

"2) then why did we wait for bad results to say so????? Would we have said the same thing if results were particularly good?? Certainly not."

Certainly yes! When the CR Society held its meeting at the University of Wisconsin, we were all aware that the monkeys, both the CR cohort and the controls, were on hunger strike. We thought then that the study was cruel incarceration. Throughout the history of the study, problems have surfaced with getting the monkeys to follow the protocol.

Ok everyone, nothing to see: it has always been obvious that the NIA study should be dismissed without waiting for its results ...

(I am being sarcastic to make the point but don't take me wrong, this is not directed to anyone, it is to progress scientifically: if such an answer had been given the same day as the paper was mentionned on forums then I would have accepted it more easily; but here, it is sincerely difficult to accept such a late argument that is essentially a saying and a pure opinion, to ignore uncomfortable results. Can't we scratch the surface a little more? or are you aware of something the authors are ashame of and you think would be preferable to hide?)

To start with, is there some possibility that the military place can tell us what type of experiments were performed on the monkeys?
To continue, can we reproduce the bad CR in rodents?
Also, shouldn't we at least have observed some tendency of longer lives in the monkeys that had good CR signals?
Lastly, if you consider CR experiments in monkeys to be cruel incarceration, why isn't it in rodents and... why isn't it in (volunteering; I know but still) humans?

Edited by AgeVivo, 16 September 2012 - 02:52 PM.

[scottknl]

Heh he, AgeVivo. You have a funny definition of cruel "Not being allowed to eat everything you want". No, the cruelty is simply from the incarceration of the animals, not the dietary treatment. 30% CR in humans is not cruel or even particularly uncomfortable. I do it all the time.

[AgeVivo]

You have a funny definition of cruel

I have made the point a bit big. CR works in many emprisoned species.

[sthira]

When the CR Society held its meeting at the University of Wisconsin, we were all aware that the monkeys, both the CR cohort and the controls, were on hunger strike. We thought then that the study was cruel incarceration. Throughout the history of the study, problems have surfaced with getting the monkeys to follow the protocol.

Were the CR monkeys at UW given open space and time to play and care and bond with each other? Were they allowed to make friends, form alliances, groom one other? Or were they all locked down individually with no tactile contact? Were they just stuck in stacked cages under bad lighting in a university lab? For years? If so, eek, that's entirely relevant.

Everyone who has worked with captive primates should know they need open space; playful, political interactions; intellectual stimulation; access to a variety of nutritious food -- even if that food is 30% calorie restricted. These are intense, smart, complex individuals, and each has hir own unique personality. When caged, isolated, "incarcerated" and only eating dried up crappy ole salty chow day after day, well.. they're "unhappy" (how anthropomorphic is that?)

Did anyone in the CR Society actually tour the facility? UW has a highly respected primate center, and I have a difficult time believing only the hard-hearts were in charge over these monkeys. Are any of the research assistants who actually did the husbandry work of feeding, cleaning cages, caring for and talking to these monkeys reading this and available for comment on their real life housing conditions?

[pmcglothin]

Fact is that if you are following a CR Diet certain basic physiological things happen: Lower triglycerides, T3, glucose, etc. If that's not happening, something is wrong with your approach...

But it did happen, in the adult-onset NIA monkeys. So if you are unhappy with the study, you would have to demonstrate in what way they early-onset monkeys' CR diet differed from that of the later-onset monkeys.

You would also have to explain why the group of adult-onset CR monkeys in the NIA study whose biomarkers improved did not live longer.

Yes. We could spend hours on that and speculate. A better use of time would be to demonstrate that CR (with the right approach) downregulates pathways that slow aging in every mammalian species. We are doing that in human CR research. Dr. Fontana has done an excellent job. It has been a major focus of the last decade. New studies will be out about this over the next year or so.

Consider the mTOR pathway for example, which is stimulated by total calories, total protein, easily absorbable protein (especially when high in leucine), and high glucose levels. When this fearsome kinase is activated – then bye-bye CR benefits. It is pretty obvious from looking at the diet of the NIA study (provided in the full paper I shared in response to AgeVivo that the researchers did not have ideas like this in mind 25 years ago. That I do not fault them for. We could not expect them to see into the future.


Paul

[pmcglothin]

When the CR Society held its meeting at the University of Wisconsin, we were all aware that the monkeys, both the CR cohort and the controls, were on hunger strike. We thought then that the study was cruel incarceration. Throughout the history of the study, problems have surfaced with getting the monkeys to follow the protocol.

Were the CR monkeys at UW given open space and time to play and care and bond with each other? Were they allowed to make friends, form alliances, groom one other? Or were they all locked down individually with no tactile contact? Were they just stuck in stacked cages under bad lighting in a university lab? For years? If so, eek, that's entirely relevant.

"Wow. Finally someone who recognizes the importance of the incarceration aspect! I am not swayed by comparisons to mice and certainly not to calorie restricted humans. If calorie restriction is done right, it is one of the happiest ways to live!"

Sthira wrote:

"Everyone who has worked with captive primates should know they need open space; playful, political interactions; intellectual stimulation; access to a variety of nutritious food -- even if that food is 30% calorie restricted. These are intense, smart, complex individuals, and each has hir own unique personality. When caged, isolated, "incarcerated" and only eating dried up crappy ole salty chow day after day, well.. they're "unhappy" (how anthropomorphic is that?)"

Of course!

Sthira wrote:

"Did anyone in the CR Society actually tour the facility?" UW has a highly respected primate center, and I have a difficult time believing only the hard-hearts were in charge over these monkeys. Are any of the research assistants who actually did the husbandry work of feeding, cleaning cages, caring for and talking to these monkeys reading this and available for comment on their real life housing conditions?

We were not invited to tour the facility and did not press it. Take a look at the attachment I provided to AgeVivo. It provides a description of their housing conditions. It states that the rhesus monkeys were isolated to keep them from fighting. That indicates to me they are not ideal for primate studies.

I do think the researchers were diligent about cage cleaning, but a AFAIK the rhesus monkeys have remained isolated for their entire lives.

Want to find out a little more about the study conditions at the top monkey research centers? Try This:

http://www.primatefr...ingkemnitz.html

I do not find it surprising that monkeys held in small cages inflict wounds on themselves. I'll bet many of them would commit suicide if they knew how.


Paul

[kismet]

Thank you for the Ingram paper!

Let me say, for now, I really doubt the studies are methodologically worthless. All The primates are doing well as far as longevity is concerned.

MR will write an article addressing this & other issues sometime...

[albedo]

Eager to read MR's reply ...

[AgeVivo]

[Luminosity]

I'm glad I could at least make you realize how tactless they were.

By the same logic, you could fight a fire by throwing gasoline on it.

I came here to ask the administrators to remove my earlier posts but once again, you changed my mind, Chupoman. I guess they will stand.

[JLL]

Funny "logic" here from the CR supporters. Apparently we know for 100% certain than CR increases lifespan in all species and lowers triglycerides etc. and since these monkeys had higher triglycerides, we can conclude that they weren't actually on CR.

Where has it been proven that animal CR needs contact with other animals, plenty of space, etc. to work?

Regardless of what the CR society thought of the animals being incarcerated before the results came in, I bet they would not have dismissed the results had they been positive. In fact, it would've been even stronger proof in their mind -- "See, CR works even under terrible conditions, let alone in optimal conditions!"

[scottknl]

Funny "logic" here from the CR supporters. Apparently we know for 100% certain than CR increases lifespan in all species and lowers triglycerides etc. and since these monkeys had higher triglycerides, we can conclude that they weren't actually on CR.

Where has it been proven that animal CR needs contact with other animals, plenty of space, etc. to work?

Regardless of what the CR society thought of the animals being incarcerated before the results came in, I bet they would not have dismissed the results had they been positive. In fact, it would've been even stronger proof in their mind -- "See, CR works even under terrible conditions, let alone in optimal conditions!"

One of the suggested explanations for the unexpected results was that the control animals were throwing away their food because they were unhappy with their living conditions. So as a result the controls were CR'd to a much greater degree than designed into the experiment and both groups lived statistically similar lifespans. I'd find it hard to believe that the CR group would have thrown away very much food.

Perhaps the chimps were a bit too intelligent to be useful for such a long time experiment and this caused many of the behavior problems.

I would have been happy if the study validated my world view. That didn't happen, so I need to either change my view that CR works as a longevity promoter or find some other reason why the study was faulty. There's no denying the health promoting effects though. No cancer at all and a reduced risk of diabetes and heart disease vs the control group is a good result in the NIA study. I expect even better performance from the WNPRC study given their reported interim results on diabetes from 2009.

It is strange that the triglycerides levels of the animals didn't respond to CRON when many CRONIES find that triglycerides on an optimal diet don't increase with age. Could that be a diet issue? I think it's a valid question to ask.

Anyway I doubt very much that CR will get much further funding for additional long term studies due to this finding, so we'll never know. Even when the Wisconsin study reports in a few years, people will still point to this NIA study and say CR doesn't work for longevity.