214 replies to this topic

[Guest]

As the CR-Society response was refering to AMP-activated protein kinase I have two things to add.

First the role of AMPK as a "major facilitator" of CR is speculative at best given the evidence:

http://physiologyonl...t/26/4/214.full


As the review nicely outlines, the causal relationship and the priniciple role of AMPK in CR is unclear.

Second, even if AMPK plays a direct causal role in CR, is it activated independently of physical exercise by doing calory restriction alone - hence the 50% life extension we see in short lived rodents. This also means (ASSUMING the CR-Society is right about AMPK), that lack physical exercise does not inhibit activation of AMPK by CR alone. Consequently there should have been a CR lifespan effect in the CR-monkeys if observations in mice are translatable to primates.

[Guest]

Well... scientists somewhere in the world are devising a CR primate study that addresses the shortcomings in the latest studies. We'll get the results in another 20 or 30 years. In addition by then we'll have the results from dozens of other studies that will refine our understanding of how CR works.

In the meantime my money is on exercise + CR.

Why? Because evolution favored both.

If you want to do something different or wait for more research it's your prerogative.

You are avoiding the argument. The monkey trials do not support the theory, that long lived species will benefit from CRON at the moment. There are methodological problems, yes, but it is highly unlikely that lack of exercise is a relevant factor in the outcomes.


If you are going to do severe life style choices based on no (scientific) evidence, "it's your prerogative".

[scottknl]

Well... scientists somewhere in the world are devising a CR primate study that addresses the shortcomings in the latest studies. We'll get the results in another 20 or 30 years. In addition by then we'll have the results from dozens of other studies that will refine our understanding of how CR works.

In the meantime my money is on exercise + CR.

Why? Because evolution favored both.

If you want to do something different or wait for more research it's your prerogative.

You are avoiding the argument. The monkey trials do not support the theory, that long lived species will benefit from CRON at the moment. There are methodological problems, yes, but it is highly unlikely that lack of exercise is a relevant factor in the outcomes.


If you are going to do severe life style choices based on no (scientific) evidence, "it's your prerogative".

TFC, you are incorrect when you say

The monkey trials do not support the theory, that long lived species will benefit from CRON at the moment.

The reason you are incorrect is that the NIA and WNPRC studies both clearly showed significant reduction in the diseases of aging when comparing the control group with the CR group. This is clearly a benefit from CRON.

Also you're incorrect when you say

If you are going to do severe life style choices based on no (scientific) evidence, "it's your prerogative".

The reason you're incorrect is that there is a lot of evidence that suggests that CR is very healthy in humans when properly implemented. Dr. Luigi Fontana has published several studies on human parameters. He's also compared exercise groups with CR groups and found that the CR group is generally healthier. In addition to the human health parameters evidence, we also have the primate evidence in which the NIA and WNPRC studies both clearly showed significant reduction in the diseases of aging when comparing the control group with the CR group. Edit: I consider both humans and other primates (30+ years old) to be long lived species.

DR01D, I truly wish you were right with your exercise + CR assertions, but this too is wrong. It has been tested with rats on CR and CR+EX lived just the same lifespan as CR alone. I believe this is sufficient to conclude that there's no need to test it in higher species. Perhaps in the wild, the survival benefit for being larger and stronger might be useful in some species.

I also exercise and enjoy it, but I don't delude myself that it's going to make me live any longer. Where I live I don't have to wrestle my meals away from other people or animals, so being stronger just means eating more calories. However, I can catch the transit bus quicker that the rest of the fatties around me, so I never miss my ride!

Edited by scottknl, 20 November 2012 - 10:14 PM.

[Guest]

TFC, you are incorrect when you say

The monkey trials do not support the theory, that long lived species will benefit from CRON at the moment.

The reason you are incorrect is that the NIA and WNPRC studies both clearly showed significant reduction in the diseases of aging when comparing the control group with the CR group. This is clearly a benefit from CRON.

Also you're incorrect when you say

If you are going to do severe life style choices based on no (scientific) evidence, "it's your prerogative".

The reason you're incorrect is that there is a lot of evidence that suggests that CR is very healthy in humans when properly implemented. Dr. Luigi Fontana has published several studies on human parameters. He's also compared exercise groups with CR groups and found that the CR group is generally healthier. In addition to the human health parameters evidence, we also have the primate evidence in which the NIA and WNPRC studies both clearly showed significant reduction in the diseases of aging when comparing the control group with the CR group. Edit: I consider both humans and other primates (30+ years old) to be long lived species.

Well, I should have mentioned that I was refering to the life extension effect of CR seen in short lived animals. Of course I acknowledge, that there are established effects on health-parameters. But it does not seem to translate into longer life spans in primates.

[DR01D]

DR01D, I truly wish you were right with your exercise + CR assertions, but this too is wrong. It has been tested with rats on CR and CR+EX lived just the same lifespan as CR alone. I believe this is sufficient to conclude that there's no need to test it in higher species. Perhaps in the wild, the survival benefit for being larger and stronger might be useful in some species.

I also exercise and enjoy it, but I don't delude myself that it's going to make me live any longer. Where I live I don't have to wrestle my meals away from other people or animals, so being stronger just means eating more calories. However, I can catch the transit bus quicker that the rest of the fatties around me, so I never miss my ride!

Well I think we might be talking about two different things. You are right, exercise does not extend maximum lifespan. However it increases average lifespan and it certainly increases healthspan.

I practice CR and exercise so that I can reach my natural potential. If I'm lucky that might be 100 years +/-. An average, sedentary, obese man should make it to his 70s +/-. So to me that's a huge improvement.

Will I reach 120 or more with CR and exercise? Eeeee... probably not. I don't think either has a large effect on maximum lifespan in humans.

Edited by DR01D, 21 November 2012 - 01:42 AM.

[maxwatt]

I have yet to meet a 92 year old whose position I would want to be in.

[DR01D]

I have yet to meet a 92 year old whose position I would want to be in.

I have yet to meet an obese, sedentary 40 year old whose position I would want to be in.

[maxwatt]

At 40, it's easy to say it's the fatty's fault. But in extreme age not so much. Nor are there sufficient interventions at this point to prevent such deterioration. And without a relatively modest but orders of magnitude greater than currently allocated cash infusion into research on aging, there likely won't be such interventions when you need them.

[scottknl]

I have yet to meet a 92 year old whose position I would want to be in.

I hope that I'd rather switch with Matt or Johann when they're 92.

Seriously though, it's only by studying the mechanisms of CRON, rapamyacin and the other true anti-aging compounds that we're really going to understand why they work and whether and how we can improve their effects. Maybe even stem cell and telomere lengthening therapy will play a critical role.

Poorly conceived experiments like the NIA and WNPRC studies really muddy the waters and don't create the environment for raising aging research dollars that we all need to hit our longevity goals.

Exercise alone definitely won't get you to an advanced age. Jack Lalanne is an example. Despite leading a lifestyle of healthy food (but no CRON) and lots of exercise his own immune system killed him. I really hope we can create some immune system therapy to improve our immune system defenses when we age.

[maxwatt]

Actually Lalanne was one 92year old I wouldn't mind being. But at 93, not so much.

BTW, his later years I think were Vegan and semi CRON

[DR01D]

Jack LaLanne made it to age 96 and had incredible health until his last couple of years.

He lived on a low calorie, natural food, 2 meal per day diet.

He ate two meals a day and avoided snacks. His breakfast, after working out for two hours, consisted of hard-boiled egg whites, a cup of broth, oatmeal with soy milk and seasonal fruit. For dinner he and his wife typically ate raw vegetables and egg whites along with fish. He did not drink coffee.

His strategy of exercise, strength training and low cal is spot on. Way ahead of his time.

[trance]

His mom lived to 89, his brother lived to 97 ... so genetics played its role.

[DR01D]

His mom lived to 89, his brother lived to 97 ... so genetics played its role.

You're correct. But I wouldn't automatically attribute that to heredity.

Nature: Paper on genetics of longevity retracted

Previous studies have suggested that tiny contributions from hundreds of genetic factors combine to account for about 25% of variation in human longevity. The remaining 75% is attributable to environmental influences.

Knowing this, Anatoli Yashin, a biostatistician at Duke University in Durham, North Carolina, was sceptical of Sebastiani and Perl's paper from the start. "I didn't believe it," he says. "Any model that plans to predict lifespan based only on genetic components is not quite correct. The environmental contribution to longevity is huge."

Family members share a lot more than genes.

Behaviors, bacteria, ideas and a thousand other things are shared among family members.

Edited by DR01D, 23 November 2012 - 01:51 AM.

[xEva]

... it's only by studying the mechanisms of CRON, rapamyacin and the other true anti-aging compounds that we're really going to understand why they work and whether and how we can improve their effects. ...

Poorly conceived experiments like the NIA and WNPRC studies really muddy the waters and don't create the environment for raising aging research dollars that we all need to hit our longevity goals.

But what if NIA and WNPRC experiments were fine? What if they underscored the metabolic differences between the short-lived mammals like mice and the longer-lived mammals like primates? If it is true that a 24-h fast for a mouse is metabolically equivalent to a week-long fast for a man, then these studies imply that it is true fasting that extends life, not simple daily CRON. Long-term fasting (a week+) switches on the repair mechanisms that are inaccessible in other metabolic states.

The next monkey study should include the 3rd group. That group should consume the same amount of calories --per year-- as the restricted group, except that their restriction should come as fast days and even weeks. Their ration should also be limited on the coming-out-of-fast days and be the same as for ad lib animals on other days. This 3rd group could show a significant extension, similar to mice.

True fasting repairs the damage already done; CRON only slows it down. 40% restricted mice show the same metabolic markers as a human fasting for a week. Think about it

[trance]

Family members share a lot more than genes.

Behaviors, bacteria, ideas and a thousand other things are shared among family members.

All of those "things" are far more variable, especially among any two lives separated by 8 years time in the very early 20th century, then possibly the genetics of having been born from the same parents.

Jack's brother lived to 97 years, never adopting his younger brother's lifestyle, and Jack lived to 96 years, promoting fitness & diet most every day of his life.

Did the exercise and lifestyle, or lack of it, make much difference in these two samples?

[DR01D]

Did the exercise and lifestyle, or lack of it, make much difference in these two samples?

Previous studies have suggested that tiny contributions from hundreds of genetic factors combine to account for about 25% of variation in human longevity. The remaining 75% is attributable to environmental influences.

I believe that estimate is more or less correct.

If Jack Lalanne and his brother lived to the same age maybe 25% +/- of that was due to heredity. As siblings they only shared half of their genes.

Also you have to ask how many of Lalanne's relatives lived average or even short lives? Probably many.

250,000 years of natural selection has provided most of us with good genes. It's the environment we have to look out for.

[scottknl]

... it's only by studying the mechanisms of CRON, rapamyacin and the other true anti-aging compounds that we're really going to understand why they work and whether and how we can improve their effects. ...

Poorly conceived experiments like the NIA and WNPRC studies really muddy the waters and don't create the environment for raising aging research dollars that we all need to hit our longevity goals.

But what if NIA and WNPRC experiments were fine? What if they underscored the metabolic differences between the short-lived mammals like mice and the longer-lived mammals like primates? If it is true that a 24-h fast for a mouse is metabolically equivalent to a week-long fast for a man, then these studies imply that it is true fasting that extends life, not simple daily CRON. Long-term fasting (a week+) switches on the repair mechanisms that are inaccessible in other metabolic states.

The next monkey study should include the 3rd group. That group should consume the same amount of calories --per year-- as the restricted group, except that their restriction should come as fast days and even weeks. Their ration should also be limited on the coming-out-of-fast days and be the same as for ad lib animals on other days. This 3rd group could show a significant extension, similar to mice.

True fasting repairs the damage already done; CRON only slows it down. 40% restricted mice show the same metabolic markers as a human fasting for a week. Think about it

If the NIA and WNPRC experiments actually reflect reality and CR can't induce longevity, but can induce exceptional resistance to the diseases of aging, then we still have a great tool for those with strong will power to maintain their health. I find your theory that mice experience some speeded up version of metabolism to be very far fetched an unlikely to be true. In my mind its much more likely that we will find that longer lived species have more mechanisms for repairing damage and this is why they live longer. The experimental papers I've read comparing different intermittent fasting regimens and CRON seem to reduce to any life extension is proportional to the reduction in energy, regardless of the timing of the delivery of calories. I'm certainly willing to read any papers you'd care to reference on fasting that show otherwise.

I seriously doubt there will be a next monkey study after the expensive, inconclusive fiasco that this pair of studies creates as to the longevity question. As I stated before, science will likely render better results with less animal torture by focusing on the epigenetic factors in shorter term studies. It will be hard to raise the money for such studies given the results presented from the NIA. Perhaps I'm wrong... only time will tell.

Both CRON and fasting allow the body to shift the balance of energy usage to repair work vs growth.
I'd love to see any kind of paper that shows that fasting is superior to an isocaloric equivalent CRON diet in animals or humans. If it hasn't been done yet, perhaps we could suggest it to Dr. Luigi Fontana and see if he'd be interested in setting something like that up. I guess either way your longest lived will be skinny.

[AgeVivo]

*IF* CR had a very limited lifespan effects on monkeys (so far the conditions of the experiments I think are too complex and obscur to conclude; if it had to be redone it should be open science, eg continuously filmed and with very transparent knowledge about the history and conditions of the monkeys, and better design of food), would it mean than some types of mouse-life-extending treatments should have very limited effects in humans? would there be a way to flair which ones?

A an exemple, by definition CR would not work well in humans
As a possible counter exemple FOXO3A families live longer throughout the globe.

[AgeVivo]

A few thoughts/my 2 cents to approach the question I just raised:

I find your theory that mice experience some speeded up version of metabolism to be very far fetched an unlikely to be true. In my mind its much more likely that we will find that longer lived species have more mechanisms for repairing damage and this is why they live longer.

I feel that the 2 points of view are simultaneously true // this is essentially a feeling based on constant interest and attention on any report regarding diseases/frailty versus age in mice and humans:
- we do have a much better machinery than mice to repair/resist to much damage (coffee, growth hormone, lots of toxics compounds...) and it might be one of the needed things for us to live much longer
- mice do age somewhat similarly than us but about 30 times faster: they develop cataracts, cancers, heart failure and general frailty about 30 times faster than us

Now, imagine that humans were to be selected to live longer. If families that have bad risks of cardiac, cancer and neurodegenerative diseases were disapear (evolutionary point of view), would it lead to humans who leave longer but end up also having similar diseases? If not it suggests that between mice of humans something else is going on, perhaps a length of life during which renewal of the body is sufficient.

One experiment could be to select mouse strains to naturally reduce the risks of cancers, and see how the disease profile evolves. Such data is probably already available by comparing the various risk profiles of lab mouse strains.

[scottknl]

A few thoughts/my 2 cents to approach the question I just raised:

I find your theory that mice experience some speeded up version of metabolism to be very far fetched an unlikely to be true. In my mind its much more likely that we will find that longer lived species have more mechanisms for repairing damage and this is why they live longer.

I feel that the 2 points of view are simultaneously true // this is essentially a feeling based on constant interest and attention on any report regarding diseases/frailty versus age in mice and humans:
- we do have a much better machinery than mice to repair/resist to much damage (coffee, growth hormone, lots of toxics compounds...) and it might be one of the needed things for us to live much longer
- mice do age somewhat similarly than us but about 30 times faster: they develop cataracts, cancers, heart failure and general frailty about 30 times faster than us

Now, imagine that humans were to be selected to live longer. If families that have bad risks of cardiac, cancer and neurodegenerative diseases were disapear (evolutionary point of view), would it lead to humans who leave longer but end up also having similar diseases? If not it suggests that between mice of humans something else is going on, perhaps a length of life during which renewal of the body is sufficient.

One experiment could be to select mouse strains to naturally reduce the risks of cancers, and see how the disease profile evolves. Such data is probably already available by comparing the various risk profiles of lab mouse strains.

The mice have self selected evolutionary in favor of reproduction and rapid growth to full size. The price they pay for this is much higher cancer rates. Mice don't have much in the way of heart disease AFAIK because they don't have enough time to develop atherosclerosis and as such, are not a good model for testing for heart problems. Much of the research I've read seems to point to rate of growth and repair on the same continuum. If you have faster growth, then you make more mistakes (DNA errors) possibly from localized shortages of resources. If you have slower growth, then you have fewer errors, but it takes longer to have a full set of tools to defend yourself against predators. So my point is that the reason mice die so quickly is a combination of badly constructed proteins which likely result in higher oxidative damage and also a lack of mechanisms to repair DNA damage. Longer lived animals have more mechanisms to repair damage and keep DNA damage from accumulating quickly and since they generally take a longer time to grow to full size, there are fewer errors to correct.

MR has a theory of cell wall fatty acid composition that suggests that the ratio of omega-6/3 is related to how susceptible a cell is to oxidative damage and that the ratio might differ from species to species. I think it makes sense at first glance and might be an important piece of the puzzle.

I'd suspect that your anti-cancer mice might be slower growing generation after generation. You might even wind up with naked mole rats

So in summary, I'd suggest that mice metabolism is not simply speeded up, it's just more error prone so damage accumulates faster and causes death 30x sooner.

[xEva]

I find your theory that mice experience some speeded up version of metabolism to be very far fetched an unlikely to be true.

This is not my theory but a fact. These facts were brought up several times on the board and there are at least 2-3 threads dedicated to these metabolic differences between mice and men. One of the threads, by Brett Black, is very well argued and documented.

Just to list here a few of these facts: the mouse heartbeat rate is 600 per minute and they loose 10% of their weight after a 24h fast, and 20% after 48 hours (compare this to a man). Then there is a thread prompted by the study that 40% restricted mice show metabolic markers of a man fasting for a week. Those threads have plenty of references, including quotes by several specialists in this kind of research stating in one voice that mouse metabolism is about 7-8 times faster than human.

These facts are worth knowing for all those who readily model their lifestyle and diet based on the rodent studies

The unanswered question we all want to know is what exactly extends life in food restricted rodents. Is it simply the amount of calories consumed -- or is it due to the profound metabolic changes they experience in between feedings? You cannot deny that those profound metabolic changes do take place, because that too is a fact. Not a theory. The simplistic theory most here advocate is that the extension is all due to the diminished amount of calories consumed. The monkeys studies imply otherwise.

The experimental papers I've read comparing different intermittent fasting regimens and CRON seem to reduce to any life extension is proportional to the reduction in energy, regardless of the timing of the delivery of calories. I'm certainly willing to read any papers you'd care to reference on fasting that show otherwise.

Again, IF and CRON studies were all done on rodents, sometimes by 'researchers' lacking understanding of the severity of metabolic changes rodents experience in such a short, by our standards, span. The humans who engaged in IF simply applied those studies to themselves, expecting the same benefits, without taking aforementioned facts into account or bothering scaling the time parameters to adjust for vastly different metabolic rates.

And I understand why most cronies like you or MR are so much against fasting. With your BMIs it is your instinct telling you --correctly!-- that you don't have enough resources to safely engage in a real fast. And indeed you should not fast beyond a day or two. The rest of us, with BMIs of 19+, are not so limited in our choices.

Both CRON and fasting allow the body to shift the balance of energy usage to repair work vs growth.

I'd love to see any kind of paper that shows that fasting is superior to an isocaloric equivalent CRON diet in animals or humans.

There is no such studies to my knowledge. But again, what is the question here? IMO, the question is, what exactly extends life in food restricted rodents, i.e. what is the mechanism. I propose that the mechanism is in metabolic state they achieve in between feedings, and it is that of a fasting man. A human needs to fast to achieve those metabolic markers, but a 24h IF for a human is not a fast proper; it's properly called eating once a day lol. It's a real fast for a mouse though, for the thing will loose 10% of its body weight and show profound hormonal changes.

[AgeVivo]

Question: *if* CR doesn't work in primates, what types of mouse gerontodrugs should also work/not work in primates?

PS1: answer is neither none nor all, as described above
PS2: compared to primates, mice have both an accelerated metabolism and a less protective metabolism, as described above

[Turnbuckle]

PS2: compared to primates, mice have both an accelerated metabolism and a less protective metabolism, as described above

The biggest difference: mice DNA have enough telomeres to last several lifetimes, so their life spans are most likely limited by their mitochondria. In humans (and primates), lifespan is likely limited by both mitochondrial dysfunction and the eroding of telomeres.

Edited by Turnbuckle, 25 November 2012 - 02:07 PM.

[Guest]

Are there still no replies, that somewhat convincingly argue, why the monkey studies do not imply, that CR does not extend life span in long lived mammals?

The last one from the CR-society did just summarize the results and tried to disregard the relevance of the unfavourable results by talking about "unnatural" living conditions and lack of exercise (which in their theory appaerently specifically disabled the CR-genetics *sights*). As we concluded, the "unnatural" upbringing is unlikely to specifically disable CR-genetics and certainly not to a point where CR-effects vanish completely.

Meaning that CR-genetics were active - and it just does not extend life span in long lived mammals.



Any further ideas about countering this uneasy conclusion? I would be especially interested in arguments that incorporate coherent thoughts about oddities in the biomarkers of the NIA-study.

[scottknl]

Are there still no replies, that somewhat convincingly argue, why the monkey studies do not imply, that CR does not extend life span in long lived mammals?

The last one from the CR-society did just summarize the results and tried to disregard the relevance of the unfavourable results by talking about "unnatural" living conditions and lack of exercise (which in their theory appaerently specifically disabled the CR-genetics *sights*). As we concluded, the "unnatural" upbringing is unlikely to specifically disable CR-genetics and certainly not to a point where CR-effects vanish completely.

Meaning that CR-genetics were active - and it just does not extend life span in long lived mammals.



Any further ideas about countering this uneasy conclusion? I would be especially interested in arguments that incorporate coherent thoughts about oddities in the biomarkers of the NIA-study.

So in summary, WNPRC so far shows us that crappy diet CR beats control easy on lifespan. NIA shows us that better quality diet light CR (~10%) is as effective as medium CR (25%) (weep on your knees CR (40+%) wasn't tested) for lifespan. Both studies have shown clear effects on health parameters that far exceed the best that can be done with modern drug regimens. In particular the NIA study shows a control regimen has been demonstrated that dramatically increases lifespan in a sedentary environment when compared to normal feeding regimens for this species. We also have a big reminder that in this species male vs female lifespans are significantly different.

By far the biggest problem with the NIA experiment was the reduction of food intake by the control group in advanced age. This is really a huge con founder.

Further conclusions will have to wait for more data. I think it's likely that the reason others haven't commented is that there's not enough data to form a conclusive argument either way.

[xEva]

So in summary, WNPRC so far shows us that crappy diet CR beats control easy on lifespan. NIA shows us that better quality diet light CR (~10%) is as effective as medium CR (25%) (weep on your knees CR (40+%) wasn't tested) for lifespan. Both studies have shown clear effects on health parameters that far exceed the best that can be done with modern drug regimens. In particular the NIA study shows a control regimen has been demonstrated that dramatically increases lifespan in a sedentary environment when compared to normal feeding regimens for this species. We also have a big reminder that in this species male vs female lifespans are significantly different.

By far the biggest problem with the NIA experiment was the reduction of food intake by the control group in advanced age. This is really a huge con founder.

Further conclusions will have to wait for more data. I think it's likely that the reason others haven't commented is that there's not enough data to form a conclusive argument either way.

Yes, the only sure thing is the healthspan extension, which in itself is pretty good. Of course, it would be better if it was accompanied with longer lifespan too...

..and it's interesting that the ad lib monkeys restricted themselves in old age, just like old humans tend to do.

Any further ideas about countering this uneasy conclusion? I would be especially interested in arguments that incorporate coherent thoughts about oddities in the biomarkers of the NIA-study.

What oddities in the biomarkers? Would you mind posting a summary on that?

[DR01D]

Both studies have shown clear effects on health parameters that far exceed the best that can be done with modern drug regimens.

That's the big deal for me. Maybe I won't live past 90 but at least I get to have a full, healthy life while I'm on Earth. Most people who eat a normal, western diet are obese and in serious decline by age 50.

Edited by DR01D, 09 December 2012 - 05:38 AM.

[scottknl]

...snip...

“If you’re in a single cage for your whole life, and are a highly intelligent animal like a primate, deprived of contact with other peers, and on top of that you’re calorically restricted — can you imagine the psychological depression issues that will ensue?” said Fontana. “And we know the hypothalamus in the brain is a major regulator of many downstream metabolic factors.”

"Fontana pointed out that key hormonal changes found in both calorie-restricted mice and humans were not detected in either group of monkeys, an absence that he blames on their relatively high-protein diet.

also

"The female monkeys "P50.0276).Specifically, CR males had lower triglycerides than control males. By contrast, CR females
had higher triglyceride levels than control females""
...snip...

I need time to go over the paper again and review other papers related to the study. But just my initial thoughts on the study below:

Although they eat less (Supplementary Table 2) and weigh less13, young-onset CR monkeys lack many of the expected CR benefits. Fasting serum glucose levels were not significantly lower in the CR monkeys compared to control (Fig. 2c), and only the CR males had somewhat lower triglycerides compared to respective controls (P50.051)

...snip...

Another startling consequence of the NIA study is the alleged decoupling of healthspan from lifespan

If you look at the 'health' of the CR animals their results were far from impressive. CR females having significantly higher Triglycerides than the female control group. Cholesterol levels not improving in the female group. No improvement in fasting serum glucose for the adult onset rhesus monkeys. I'm not aware of the typical difference in lifespan between female and male rhesus monkeys but 27.8 years vs 35.4 years. I know that for most species it's the females that typically live longer. The monkeys according to Dr Luigi Fontana did not show the same hormonal changes with their IGF-1 as is proven over and over again to be important in longevity in animals and in humans.
...snip...

Right. Look at the fasting glucose level rise in the CR monkeys just as the ad lib group for Males *shrug* see attached file. To me it looks like they screwed up. They didn't respond in the same way mice do and even humans are. The female survival curves look terrible also. Look at the fasting serum Triglycerides for the female CR monkeys. :o It seems monkeys are being killed off early by a crappy diet? lol


Figure 1 | (left column a) Survival curve and triglycerides, cholesterol and glucose levels for
old-onset monkeys.


Figure 2 | (right columns a/b) Survival curves and glucose and triglycerides levels for youngonset
monkeys
http://www.longecity...attach_id=10310

http://www.physiolog...s/Kemnitz35.pdf You should take a read of that. It explains the WNPRC study and also some results they had earlier on. A couple points from the WNPRC

"IGF-1 and IGFBP-3 were also
measured at the 42- and 54-month assessments in the Group 1 animals from our DR
study and no effect of DR was observed for either measure at these time points."

"In contrast to rodent studies, we found no evidence for a decrease in T3 with DR in monkeys (Fig. 7).
We have seen no consistent age-related trends in T3 levels for the animals in Group 1."

Both of these I believe are important for Calorie Restriction to work in animals. Not only that... IGF-1 and T3 are both implicated in longevity in humans (studies on centenarians and offspring of centenarians). No effect to these were found in this study from old data... but a reduction in T3 was found in the NIA study pmid:12189585 (old data). Humans show a reduction in IGF-1 with CR/low protein and also consistently show lower levels of T3. The monkeys studies do not show these changes that we expect when on CR. :-/
...snip...

For comparison with expected human CR test levels:

Hmm, Living the CR Way just posted this:

Calorie restriction lowers fasting glucose levels- Average glucose levels of the human CR cohort at Washington University were 81 mg/dl.¹ This makes sense since with less available energy from calories, cells burn serum glucose voraciously, causing glucose levels to fall provided that healthy, low GI carbohydrates are part of the protocol.
Calorie restriction lowers triglycerides - with less available energy, the body burns fat for fuel, so triglycerides fall. Average triglyceride level for the Washington University CR cohort was 49 mg/dL ²
Calorie restriction lowers IGF-I, Insulin-like Growth Factor, a hormone that's a major growth-driver. Ah, but this one is tricky: If protein levels are high, IGF-I stays high, whether calories are lower or not. ³ So if you want to turn down anabolic activity, a fundamental tenet of calorie restriction's effects, keep protein moderate.For anyone who doubts that calorie restriction has these effects - glucose, triglycerides and IGF-I are easy to test.

It should also go without saying that to conduct objective research on calorie-restricted humans, the subjects must not be ill nor be on medication to control an illness.
Does it not seem surprising then that the recently reported NIA study,
Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. (Nature. 2012 Aug 29. doi: 10.1038/nature11432. PMID: 22932268),

did not meet any of these criteria? These monkeys ate a high protein diet, likely to raise IGF-1 and their triglyceride and glucose levels were also uncharacteristically high. Further the cohort included previously used animals from a military research facility. Many of these animals died of illness unrelated to calorie restriction.

...snip...

So this is my summary of the posts about the triglyceride and glucose levels in the NIA study and also a comparison to what humans on CR experience. Perhaps this species of primate isn't as good a model of human CR behavior as we thought it would be.

[The Immortalist]

"Although CR has not increased mean or maximum lifespan relative to control, 50% survival for the females is 27.8 years and 35.4 years for the males, exceeding the ,27 year median lifespan previously reported for monkeys in captivity"]

(I found this interesting as it's usually females that live much longer). ... I'm trying to get my head around the difference in health and ultimately lifespan between the Female and Male monkeys. I would expect females to have a longer lifespan!! females 27 years vs males 35 years is very surprising to me And I'm wondering if lower muscle mass causing metabolic problems in the females was the cause; due to low activity. You know exercise up regulates GLUT4 receptor in the muscle improving glucose uptake improving metabolic health. Less LBM higher risk of metabolic and other problems. Low levels of activity might have affected the female monkeys more than the males. I don't know... IGF-1 is an issue as well with cancer and the diet being I think 17%? proten. With CR'd females in some areas fairing worse than the controls I think raises some questions. The response to CR is far better in the wisconsin study and better still; humans.

This is old but i wanted to respond to this post. About the females living shorter- Does pregnancy have any longevity benefits in humans and animals?

Edited by Michael, 07 April 2013 - 12:24 PM.

[Hebbeh]

This is old but i wanted to respond to this post. About the females living shorter- Does pregnancy have any longevity benefits in humans and animals?

Courtesy of 1kgcoffee...

http://www.lifesiten...ve-longer-study

http://www.standard....er-6943704.html

from the thread...

http://www.longecity...men-die-sooner/

Edited by Michael, 07 April 2013 - 12:25 PM.