214 replies to this topic

[DR01D]

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.

Scottknl I disagree with you on this point. Interest in CR will continue to increase because it works. Even rank amateurs knows that one study doesn't invalidate dozens of others.

The NIA study will help researchers produce better studies in the future.

The most important take away I got from the NIA study is that confinement or an extreme sedentary lifestyle might counteract or diminish the effects of CR. If this study convinces CRONies that they should eat an extra 100 or 200 calories per day and use it for exercise and to build/retain muscle mass it will probably end up being a bonus for their health.

Edited by DR01D, 19 September 2012 - 01:21 AM.

[Guest]

Scottknl I disagree with you on this point. Interest in CR will continue to increase because it works. Even rank amateurs knows that one study doesn't invalidate dozens of others.

The NIA study will help researchers produce better studies in the future.

The most important take away I got from the NIA study is that confinement or an extreme sedentary lifestyle might counteract or diminish the effects of CR. If this study convinces CRONies that they should eat an extra 100 or 200 calories per day and use it for exercise and to build/retain muscle mass it will probably end up being a bonus for their health.

I tend to disagree. The rhesus monkey studies are very relevant, as they are the only ones looking at long lived primates, which is as close as it can get in animal models. Years ago a couple of researchers - among them Aubrey de Grey - already pointed out, that we see diminishing returns to CRON in longer lived animals such as mice compared to shorter lived such as flys or yeast and the evolutionary response of very long lived species such as primates could be disappointing.

Essentially we now have N = 2 studies for our reference case (primates); they do not invalidate the findings in rodent studies, but the question in mind is what can we deduce from rodents at all if it comes to human CRON? For this matter it is very relevant if one of the 2 studies produces results indicating that CRON might not work in humans as it does in mice.


Anyway, without further information about the exact dietary patterns in both studies, information about the upbringing of the monkeys and other methodological details we should refrain from further judgement concerning implications for human CRON.

[scottknl]

My point was not that CR doesn't provide some health benefits, but that it gets less likely to be funded for further long term study. If a funding body has a limited set of funds and has to choose between some promising genetic research or another long term 40 year CR study... well I think the CR study has become less competitive option due to the NIA results. Also the progress in research these days makes the 40 years needed for another retry at this unlikely to be approved even if some bright minds figure out what went wrong. In other words we'll likely understand the process of CRON much better from shorter term studies before a new trial would be able to deliver final results. Possibly so much so that the enormous costs would be nearly wasted.

I think funding of shorter term studies of CR will be unaffected due to it's continued "healthspan" implications for clinical treatment and/or signalling pathway research etc..

[nowayout]

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.

They were not chimps.

[nhenderson]

Also remember that the controls were calorie restricted as well!

[AgeVivo]

For now, my take away is that lack of transparency is the main issue of this study: lifespan studies should be as transparent as possible in terms of available information; interpretation otherwise becomes extremely artistic.

[DR01D]

Essentially we now have N = 2 studies for our reference case (primates); they do not invalidate the findings in rodent studies, but the question in mind is what can we deduce from rodents at all if it comes to human CRON? For this matter it is very relevant if one of the 2 studies produces results indicating that CRON might not work in humans as it does in mice.

CR works in more than just rodents and bacteria.

Dogs Lived 1.8 Years Longer On Low Calorie Diet: Gut Flora May Explain It

Today's research, published in the Journal of Proteome Research, was based on a study in which 24 dogs were paired, with one dog in each pair given 25% less food than the other. Those with a restricted intake of calories lived, on average, about 1.8 years longer than those with a greater intake and they had fewer problems with diseases such as diabetes and osteoarthritis, plus an older median age for onset of late-life diseases.

I'm not convinced that CR will increase maximum life expectancy in humans. 100 years +/- may be our potential. But I think CR combined with lifelong physical activity (weight training, cardio, physical work, etc.) maximizes the odds that someone will reach their potential.

[Guest]

CR works in more than just rodents and bacteria.

Dogs Lived 1.8 Years Longer On Low Calorie Diet: Gut Flora May Explain It

Thank you very much for selectively quoting from my previous post and implying things I did not said. Point is, that rodents are by far the most extensively researched species for CRON and those results might not be translatable according to a couple of gerontologists - that is the sole reason for doing the primate studies (and I hope you did not intend to suggest that the dog-study could be considered on equal standing as the rhesus monkey studies).


Also the live chat with scientists involved in both studies (WIsconsin/NIA) just finished:

http://news.sciencem...imates-liv.html

unfortunately no one of you guys showed up today, so only very basic questions were raised and nothing on a level that could help to resolve our uncertainties regarding the different outcomes of the primate-trials.

[Brett Black]

To those speculating that stress from captivity may have been detrimental to the monkeys: consider that calorie restriction itself is often viewed as a form of stress (as is exercise.)

[AgeVivo]

the live chat with scientists involved in both studies (WIsconsin/NIA) just finished:

http://news.sciencem...imates-liv.html

unfortunately no one of you guys showed up today, so only very basic questions were raised and nothing on a level that could help to resolve our uncertainties regarding the different outcomes of the primate-trials.

Oh. I was not aware of it. Oh.

So no take-home-message from these primate CR studies?

[AgeVivo]

Julie Mattison: (...) for both studies we recognize that there are multiple confounders in the studies. Monkeys are a complex species and it isn't possible to eliminate all of them. Fortunately, we will have the opportunity to address some of these issues in our future collaborative work that will more closely compare the differences in study design at the two sites and try to identify the impact of these variables.

[Nootropic Cat]

the live chat with scientists involved in both studies (WIsconsin/NIA) just finished:

http://news.sciencem...imates-liv.html

unfortunately no one of you guys showed up today, so only very basic questions were raised and nothing on a level that could help to resolve our uncertainties regarding the different outcomes of the primate-trials.

Oh. I was not aware of it. Oh.

So no take-home-message from these primate CR studies?

The take-home, unless I'm mistaken, seems to be, 10% CR gives significant LE, >10% may not be better, but no one really knows until MR posts and puts us all out of our misery.

[InquilineKea]

unfortunately no one of you guys showed up today, so only very basic questions were raised and nothing on a level that could help to resolve our uncertainties regarding the different outcomes of the primate-trials.

Hahaha - SUCH a good point... Unfortunately all the basic science websites spam their Twitter/Facebook/whatever feeds with things that cater to mass audiences rather than scientists (or that try to raise their fundraising appeal) so a lot of us unsubscribe to them all. :(

I guess the most informative takehome from that convo was the message "You are correct, Peter, both studies demonstrate some improvements in healthspan."

[TheKidInside]

To those speculating that stress from captivity may have been detrimental to the monkeys: consider that calorie restriction itself is often viewed as a form of stress (as is exercise.)

for a day or two until your body gets "used to it". Obese/overweight people see healthier eating as a "stress" as well yet once they begin to shed body fat and their hormones/metabolism begins to taper down to levels of "healthy" people, it's no longer seen as stress...

as far as exercise, the only real exercise "stress" is LSD running because cortisol is raised to sustain it.

[Guest]

The discussion to date has really been good, so I thank you all for it. I'm now working on a post for the SENS Research Foundation's CSO Blog, which will give my thoughts in extensive (excessive?) detail & documentation.

Without wanting to encourage sacrificing sober research and evaluation for on-the-spot responses: do you have a rough estimate at hand about when you'll guess to be ready to comment extensively? As it appears now I would leave CRON for the time being, as the evidence for long lived primates might seem to be negative - so basically what Aubrey suspected with the evolutionary response implying a much more modest effect in long lived species. Of course I do not intend to become overweight, but the more carefree eating habits would at the moment fit my social life.... especially if there is nothing gained with CRON in terms of lifespan compared to my normal lean self that I was before doing CR.

But you are probably the best CRON-expert, so if you think differently....

Edited by TFC, 18 October 2012 - 01:11 AM.

[DR01D]

I'm always eager to read the latest scientific news and opinion but we don't have to wait another 20 or 30 years to find out what might be best for the human body.

Simply do what evolution favored.

1) Eat a very, low calorie diet
2) Reduce your feeding window from 16 hours a day to maybe 8 or 10 hours a day.
3) Eat a balanced diet containing plenty of fruits, vegetables and nuts
4) Reduce or eliminate processed foods
5) Participate in several hours of physical activity or exercise every day
6) Build muscle with strength training
7) Get some sun
8) Last but not least enjoy your time on earth

A couple of hundred thousand years of evolution optimized our brains and bodies for these behaviors.

As the monkey study suggested longevity is about more than just CR. Those animals were sitting in cages which is not so different from CR people vegetating in front of computer screens. IMHO if those animals had lived normal lives in a forest or jungle environment CR probably would have increased their healthspan and longevity. It's completely unnatural and unhealthy to sit in a cage or in front of a computer all day.

Edited by DR01D, 18 October 2012 - 08:03 PM.

[DR01D]

Reuters: Hispanics in U.S. outlive whites, blacks: report

Hispanics in the United States outlive whites by 2-1/2 years and blacks by nearly eight years, U.S. government researchers said on Wednesday, and other experts said clean living may play a role.

In spite of having less education and access to care, Latinos have a 35 percent lower risk of death from heart disease, a 40 percent lower risk of cancer, and a 25 percent lower risk of stroke than the general population, said David Hayes-Bautista of the Center for the Study of Latino Health and Culture at the University of California Los Angeles. Hayes-Bautista said the reasons are not yet clear, but he thinks it is likely due to culture and behavioral differences rather than genetics, given that U.S. Hispanics are such a diverse group.

Hispanics may have everything stacked against them including poor diets and obesity but a huge percentage of them do jobs that require steady, physical work. I think the disparity between whites and hispanics shows just how much evolution favors an active lifestyle over a sedentary lifestyle. CR is an amazing discovery but it's not everything. People need to be physically active and eat enough to support that activity. No more, no less.

Edited by DR01D, 18 October 2012 - 08:40 PM.

[DR01D]

WebMD: Hispanics Have Highest Life Expectancy in U.S.

Hispanic males' life expectancy at birth is 77.9, but their life expectancy once they reach the age of 65 is 84. Hispanic women's life expectancy at birth is 83.1 years, and this number reaches 86.7 if they live to 65, the study shows.

Japan’s Okinawa Island – The Healthiest Place on Earth

It is considered to be the healthiest place in the world, where the average life expectancy of an Okinawan woman is 86, and man’s is 78.

Both groups enjoy tremendous longevity despite the fact that as a group US Hispanics eat mountains of processed food and suffer from a high rate of obesity.

US Department of Health and Human Services: Obesity and Hispanic Americans

Among Mexican American women, 78 percent are overweight or obese, as compared to only 60.3 percent of the non-Hispanic White women.
In 2010, Hispanic Americans were 1.2 times as likely to be obese than Non-Hispanic Whites.
In 2009 - 2010 Mexican American children were 1.6 times more likely to be overweight as Non- Hispanic White Children.
From 2007-2010, Mexican American women were 40% more likely to be overweight, as compared to Non-Hispanic Whites.

The common denominator is work. Hispanics are workers and in the long run that pays off.

[Chupo]

Aren't Hispanics shorter on average? Naturally lower growth factors might have something to do with it.

[DR01D]

Aren't Hispanics shorter on average? Naturally lower growth factors might have something to do with it.

That's a good point. Hispanics are 2" or 3" shorter than whites. That could be part of the explanation.
Interestingly enough blacks in America are just slightly taller than whites.

[DR01D]

I think if low growth factors play a role in promoting longevity among Hispanics it must be low IGF-1 during childhood.

A huge number of hispanic adults are overweight or obese so they probably tend to have high IGF-1.

And yet...

Latinos have a 35 percent lower risk of death from heart disease, a 40 percent lower risk of cancer, and a 25 percent lower risk of stroke than the general population

That's probably not so different from thin people living in Okinawa.

Edited by DR01D, 22 October 2012 - 10:13 PM.

[DR01D]

I think the amazing longevity of Hispanics and the lousy results from the monkey studies is largely explained by this phenomenon.

Confirmed: He Who Sits the Most Dies the Soonest

Healthy or sick, active or inactive, the more people sat, the more likely they were to die in the next three years. Physical activity did reduce this risk significantly: the 40% higher death risk found when comparing people who sat the most to those who sat the least increased to 100% when comparing those who sat the most and exercised the least to those who sat the least and exercised the most. But while the death risk was much lower for anyone who exercised five hours a week or more, it still rose as these active people sat longer. In other words, people still need to exercise, but it's also important to spend less time sitting.

So based on that evidence here are two examples and a conclusion.

Person 1)
Diet: 1800 calories per day
Hunger: off and on all day
Lifestyle: sedentary
Body: low muscle mass
Bodyfat: 10%

Person 2)
Diet: 2200 calories per day
Hunger: off and on all day
Lifestyle: physically active all day
Body: moderate to high muscle mass
Bodyfat: 10%

IMHO both people will have excellent health but #2 will ultimately win the healthspan/longevity race.

Edited by DR01D, 24 October 2012 - 02:23 AM.

[Guest]

I think the amazing longevity of Hispanics and the lousy results from the monkey studies is largely explained by this phenomenon.

Confirmed: He Who Sits the Most Dies the Soonest

Healthy or sick, active or inactive, the more people sat, the more likely they were to die in the next three years. Physical activity did reduce this risk significantly: the 40% higher death risk found when comparing people who sat the most to those who sat the least increased to 100% when comparing those who sat the most and exercised the least to those who sat the least and exercised the most. But while the death risk was much lower for anyone who exercised five hours a week or more, it still rose as these active people sat longer. In other words, people still need to exercise, but it's also important to spend less time sitting.

I m not entirely certain that the recent posts in thread are related to resolve our uncertainties about the recently published results of the NIA-study.

As to the sitting stuff it appears to be case of reverse causation. You are probably referring to this study: http://www.ncbi.nlm....pubmed/22450936 . Think about it: they looked at 200.000 people who, at the begin of the 6-year survey, where aged 45 or older. They recorded mortality and physical activity/sitting behaviour. The only health indicator they controled for is "self reported health rating", which is a pretty subjective measure. Who would be the guys most likely to sit inside instead of walking around or doing physical acivity? Most likely the guys with an underlying disease of any sort. If you are easily exhausted due to cardiocascular problems, pulmonary problems, not getting your flue shots and therefore getting the flue etc. you are much more likely to sit inside (remember that they looked at older people). And accidently your are more likely to die, as you develop the disease.

Maybe it would be better to open a seperate topic for this.... but feel free to contribute if you can relate it to explain the different life extension effects seen in the NIA-monkeys (which is none) and the Wisconsin-monkeys (which is considerable).

[DLR]

I've been doing some PubMed searches and there are more articles that suggest CR may not be beneficial if you lose a lot of fat mass or even lean mass. Again, there's always the problem of the CR level they are imposing on the mice used in this study. As I mentioned a couple of times, 40 per cent may be too much in many strains of mice, especially they eat less than other strains of mice. There's also the problem of decreased immunity, as we can see in http://www.ncbi.nlm....pubmed/18936230. Practicing CR is getting more and more complicated if you are lean already. Let's see what MR thinks. I certainly don't know what to do.



Fat maintenance is a predictor of the murine lifespan response to dietary restriction

• Chen-Yu Liao^1,2,
• Brad A. Rikke³,
• Thomas E. Johnson^3,4,
• Jonathan A. L. Gelfond^2,5,
• Vivian Diaz²,
• James F. Nelson^1,
  Again

[nhenderson]

As to the sitting stuff it appears to be case of reverse causation. You are probably referring to this study: http://www.ncbi.nlm....pubmed/22450936 . Think about it: they looked at 200.000 people who, at the begin of the 6-year survey, where aged 45 or older. They recorded mortality and physical activity/sitting behaviour.

TFC, That was an old study. There are two or three new meta studies on this question, which control for the sick=sedentary problem. Here are two,


http://www.scienceda...20709231121.htm


http://www.scienceda...21015090048.htm

Additionally, the conclusion of the study you cited was that sitting increased all-cause mortality. The refutation to your argument is there in the study: even among those who work out a lot, mortality seems to go up with sitting. So the bias you postulate is probably not there!

Edited by nhenderson, 26 October 2012 - 06:45 PM.

[DR01D]

Practicing CR is getting more and more complicated if you are lean already. Let's see what MR thinks. I certainly don't know what to do.

Science won't provide us with a reliable blueprint for decades, maybe longer. The best we have is educated opinions based on the latest studies. But opinions change all the time. What CR advocates believe today will likely be radically different in another 10 or 20 years. I think we can all agree on that.

Since it's the year 2012 and we can't know for sure it's smartest and safest to do the things that evolution favored.

A) Eat a very low calorie diet
B) Get lots of activity and exercise every day
C) Have low but not unhealthy bodyfat
D) Have plenty of muscle mass

It's that simple.

Anybody who says different is leading people down a potentially dangerous path.

Edited by DR01D, 26 October 2012 - 07:55 PM.

[xEva]

There's also the problem of decreased immunity, as we can see in http://www.ncbi.nlm....pubmed/18936230.

This statement is too simplistic. The paper you refer to specifically involved influenza A virus, which is one of the viruses that exploit autophagy for their own replication. Authophagy is upregulated with CR, which means that such viruses will proliferate in a CR'd animal. The same autophagy is protective in most other infections, since autophagy is exactly how a cell gets rid of intracellular pathogens.

This falls under the "feed the fever starve the cold" proverb. Influenza A is one of those viruses that need to be "fed" (along with enteroviruses and rhinoviruses, etc). However, most pathogenic microbes, viruses and bacteria, do succumb to autophagy. Since in practice it is impossible to tell with certainty which bug has hit you, the best strategy is to follow your instincts. Some infections make you loose your appetite and others increase it. IMO it pays to respect your body's whims.

Refs.:
Autophagy is involved in influenza A virus replication. http://www.ncbi.nlm....pubmed/19066474
Type B coxsackieviruses and their interactions with the innate and adaptive immune systems. http://www.ncbi.nlm....les/PMC3045535/

[Mind]

Reuters: Hispanics in U.S. outlive whites, blacks: report

Hispanics in the United States outlive whites by 2-1/2 years and blacks by nearly eight years, U.S. government researchers said on Wednesday, and other experts said clean living may play a role.

In spite of having less education and access to care, Latinos have a 35 percent lower risk of death from heart disease, a 40 percent lower risk of cancer, and a 25 percent lower risk of stroke than the general population, said David Hayes-Bautista of the Center for the Study of Latino Health and Culture at the University of California Los Angeles. Hayes-Bautista said the reasons are not yet clear, but he thinks it is likely due to culture and behavioral differences rather than genetics, given that U.S. Hispanics are such a diverse group.

Hispanics may have everything stacked against them including poor diets and obesity but a huge percentage of them do jobs that require steady, physical work. I think the disparity between whites and hispanics shows just how much evolution favors an active lifestyle over a sedentary lifestyle. CR is an amazing discovery but it's not everything. People need to be physically active and eat enough to support that activity. No more, no less.

People underestimate the health contribution of exercise a great deal. Besides CR, exercise is the closest thing we have to a magic bullet against almost every aspect of aging. Believe it!

[scottknl]

I think it needs to be said that good health often results in exercise, but the reverse is much harder to do and frequently is a failed effort for many people. Thus the need for CR, paleo and perhaps other diets to create the needed level of health to support enjoyable physical activity.

[DR01D]

People underestimate the health contribution of exercise a great deal. Besides CR, exercise is the closest thing we have to a magic bullet against almost every aspect of aging. Believe it!

CR + Exercise = Magic Bullet

It's exactly what the 100 year old Indian marathoner did from this video.
http://www.longecity...ittent-fasting/
Personally I think running 26 miles is crazy but I'm not going to argue with success. You need to eat an extra few hundred calories per day to remain active. But it's worth it.

I wish the monkeys in the NIH study hadn't been caged. It would have been a much better experiment if they had lived in a more natural environment.