48 replies to this topic

[Ben K]

Lighter Meals May Bring Longer Life
Monkey study is best evidence yet that fewer daily calories boost lifespan

By Amanda Gardner
HealthDay Reporter

THURSDAY, July 9 (HealthDay News) -- A new study that found that a lower-calorie diet slowed the aging process in monkeys could be the best proof yet that restricted diets might do the same for humans.

"The big question in aging research is, 'Will caloric restriction in species closely related to humans slow aging?'" said Richard Weindruch, senior author of a paper appearing in the July 10 issue of Science. "This is the first clear demonstration that, in a primate species, we're inducing a slowdown of the aging process -- showing increased survival, resistance to disease, less brain atrophy and less muscle loss.

"This predicts humans would respond similarly," added Weindruch, professor of medicine at the University of Wisconsin-Madison and an investigator at the Veterans Hospital in Madison.

Another expert noted that, despite some highly publicized studies in certain species, the link between restricted eating and longer lifespan has been far from proven.

"The idea that dietary restriction extends lifespan in all species is not true. Many strains of rats and mice do not respond. In some strains, it's actually deleterious," explained Felipe Sierra, director of the biology of aging program at the U.S. National Institute on Aging (NIA), which supported the new study. "The fact that it didn't work in some mice but it does seem to work in monkeys is surprising and it gives us hope."

But there's a larger question: how to change humans' increasingly lax eating habits. "This [finding] doesn't give me hope that humans are going to go into dietary restriction," Sierra said.

Another expert agreed. "I think this is wonderful and it has promising benefits but the problem is not that we don't know this stuff, the problem is doing it, is getting people to eat less," added Marianne Grant, a registered dietitian at Texas A&M Health Science Center Coastal Bend Health Education Center in Corpus Christi.

As Sierra sees it, the ultimate value of this and other research like it will be to unveil the physiological mechanisms behind a slowdown in the aging process, and then come up with ways to mimic those processes with drugs or other interventions.

Previous research had shown that calorie restriction can increase survival and stave off many diseases in yeast, worms, flies and, as Sierra pointed out, in some strains of mice.

The new, two-decade-long study ultimately involved 76 rhesus monkeys, all of whom started the study as adults (aged 7 to 14 years). Thirty-three monkeys are still alive, 13 of whom are allowed to eat as they like. The other 20 are allowed a diet with 30 percent fewer calories.

Eighty percent of the original monkeys eating fewer calories are still alive, versus half of those in the control group, the researchers reported.

Among the benefits enjoyed by the lower-calorie group: fewer cancers, less cardiovascular disease, better preserved brain health (especially in regions of the brain involved in motor control and memory) and no diabetes whatsoever, despite this being a common problem in monkeys.

Weindruch said his group is continuing to study the monkeys, a process that could go on for 15 years. Meanwhile, they are collecting a new group of monkeys to more closely study mechanistic processes.

The NIA currently supports a study looking into calorie restriction in humans although, Sierra pointed out, such a study is difficult to conduct.

"Studies in humans can be done but they're not going to address longevity and it's a self-selected group," he said. "Monkeys are the closest we can get."

The findings come a day after U.S. researchers reported in Nature that rapamycin, a drug typically given to transplant patients, significantly extended the lifespans of mice.

SOURCES: Richard Weindruch, Ph.D., professor, medicine, University of Wisconsin-Madison and investigator, Veterans Hospital, Madison, Wis.; Felipe Sierra, Ph.D., director, biology of aging program, U.S. National Institute on Aging; Marianne Grant, registered dietitian, Texas A&M Health Science Center Coastal Bend Health Education Center, Corpus Christi, Texas; July 10, 2009 Science

[Michael]

All:

The paper doesn't come out 'till tomorrow; there have been a couple of press leaks, but this is from Science's own website, and cites Weindruch directly:

Calorie-Counting Monkeys Live Longer
By Michael Torrice
ScienceNOW Daily News
9 July 2009

... monkeys can live to 40, and the average life span is 27 years. Now that the surviving monkeys have reached their mid- to late 20s ... Sixty-three percent of the calorie-restricted animals are still alive compared to only 45% of their free-feeding counterparts. For age-related deaths caused by illnesses such as cardiovascular disease and cancer ... 14 versus five monkeys [have died], respectively. Another seven control and nine lean monkeys died from causes not related to aging such as complications from anesthesia or injuries. Leaner diets also reduced muscle and brain gray matter deterioration, two conditions associated with aging. (The team has not yet studied cognitive differences between the two groups.)

Researchers who study aging are split on how much stock to put in the study. Leonard Guarente ... believes that not enough monkeys have died yet to make definitive comparisons between the two groups. ... On the other hand, molecular biologist Matthew Kaeberlein ... points to the difference in age-related deaths between the two groups as the more relevant statistic. "The fact that they see a significant effect at this point suggests there will be a robust effect when they finish the study," he says.

Weindruch and his collaborators plan to continue monitoring the remaining monkeys, which could stretch the study's length past 3 decades. ...

This is the best of the 3 nonhuman primate studies, and still has some flaws: the actual differnce in Calorie intake has dwindled down to almost zero, because none of the animals are very engaged with their rather monotonous and restricted lives, so the AL eaters aren't finishing their meals a lot of the time; the food isn't the best, nutritionally, and there were definitely some specific nutritional problems (such as excessive retinol, early on) in the diets; we don't really know how how to best care for and feed nonhuman primates, nor how long they can live in captivity, because so few have been studied; and above all, there's evidence that the AL group probably should've been restricted a bit more and the CRed animals restricted even further in turn (no effects on menstruation in the females, and probably some of the AL diabetes is related to modest overweight).

But this is the first solid evidence of a real mortality difference, and it looks substantial.

-Michael

Edited by Michael, 09 July 2009 - 06:34 PM.
Clarification, fixing link

[Matt]

Did any of the researchers expect primate studies to fail given their long lifespan? Aubrey, Phelan?

It does seem very promising to me, and IMO human CR might have a better effect simply because of some of the reasons Michael already mentioned.

[AgeVivo]

Thursday, July 9th 2009 is a historical day for the promotion of life extension:
- Rapamycin [immunosuppressant treatment used in humans] extends old mice lifespan [in specific pathogen free environments]
- CR works in monkeys

We're very close to human life extension treatments!

[Matt]

From NYTimes

"Some biologists think it is reasonable to exclude these deaths, but others do not. Steven Austad, an expert on aging at the University of Texas Health Science Center, said some deaths could have been due to caloric restriction, even if they did not seem to be related to aging. “Ultimately the results seem pretty inconclusive at this point,” Dr. Austad said. “I don’t know why they didn’t wait longer to publish.”

"Leonard Guarente, a biologist who studies aging at the Massachusetts Institute of Technology, also had reservations about the findings. “The survival data needs to be fleshed out a little bit more before we can say that caloric restriction extends life in primates,” Dr. Guarente said. In mouse studies, people just count the number of dead animals without asking which deaths might be unrelated to aging, he said."
http://www.nytimes.c...ce/10aging.html


I don't really see any issue when you exclude deaths espsecially from form injuries / accidents, and from anesthesia. I don't see Austad point, there were deaths in both groups from similar things. but there were more accidental deaths in CR monkeys for whatever reason. I think It's totally reasonable to exclude these deaths that are non age related. Whats your thoughts?

the actual differnce in Calorie intake has dwindled down to almost zero

I thought this was more of a problem for the NIA studies than the Wisconsin study? I'm not sure, but I think there have been papers reporting the weight differences in the monkeys, and body fat %. There seems to be big differences where if they were eating similar calorie intake now, wouldn't these be now quite similar for both groups?

On the level of CR imposed on the monkeys, I also think it was a sensible idea [even though i believe more CR would have worked better] for them to not restrict severely in case they ran into problems many years later, which could of ended up worse because these kind of life long CR studies haven't been done in primates before. Like you said, the researchers might not know exactly whats best for the monkeys right now, increase the level of CR might of been too much of a risk.

Edited by Matt, 10 July 2009 - 02:18 AM.

[tunt01]

seems like a very grey issue.

it does kind of bother me a little that the 7 ad lib and 9 CR monkeys dying were excluded. i guess i'd want to know specifically how those monkeys died and if all the others still living experienced the same set of circumstances.

i think you need to look at the data in its entirety, and not allow for the researcher's discretion in deleting deaths from the study. it can be a slippery slope. however, i think you also have to look at the whole set of biological facts, including bloodwork/physical fitness before death and not just the death as a single datapoint.

this issue sort of brings us back the past discussion from the thread re: 'slightly overweight people living longer than thin people." if you get an injury, become immobilized, and have enough body weight/mass so that you can survive and not starve to death until you recover, than maybe the ad lib diet is better than CR.

We live in the real world, not in a sterile lab environment. If you go on CR, exhibit great telomere lengths, but you are frail/fragile and not as durable a person then it may be a trade-off in some regard.

[niner]

I don't really see any issue when you exclude deaths espsecially from form injuries / accidents, and from anesthesia. I don't see Austad point, there were deaths in both groups from similar thing. It's totally reasonable to exlude these deaths that are non age related. Whats your thoughts?

Well, I think I understand Austad's point; he's suggesting that CR might have been "responsible" for certain of the injuries, accidents, or anesthesia deaths. If CR lead to muscle wasting, maybe that lead to an accident or injury. IMHO this is somewhat far fetched. I think worrying about running the study another decade before publishing is verging on anal retentive. Do they really think that some quirk of primate biology will have the CR group suddenly drop dead in the near future?

[Dmitri]

seems like a very grey issue.

it does kind of bother me a little that the 7 ad lib and 9 CR monkeys dying were excluded. i guess i'd want to know specifically how those monkeys died and if all the others still living experienced the same set of circumstances.

i think you need to look at the data in its entirety, and not allow for the researcher's discretion in deleting deaths from the study. it can be a slippery slope. however, i think you also have to look at the whole set of biological facts, including bloodwork/physical fitness before death and not just the death as a single datapoint.

this issue sort of brings us back the past discussion from the thread re: 'slightly overweight people living longer than thin people." if you get an injury, become immobilized, and have enough body weight/mass so that you can survive and not starve to death until you recover, than maybe the ad lib diet is better than CR.

We live in the real world, not in a sterile lab environment. If you go on CR, exhibit great telomere lengths, but you are frail/fragile and not as durable a person then it may be a trade-off in some regard.

I'm currently on CR but I also have similar concerns and agree that we live in the real world not in a cage and lab. I've read that after the age of 50 people's immune systems begin to weaken which is why they're more likely to die of infectious diseases compared to younger adults (despite the advancements we've made in antibiotics, etc). CR reduces the white blood cell count and I'm concerned how that would affect the elderly with an already weakening immune system.

The reason I'm on CR despite the possible problems are that it has helped improve my health; I'm also young and many of the concerns I hold would not begin to affect me for few more decades.

[Shannon Vyff]

Here is the paper :


Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Ricki J. Colman, Rozalyn M. Anderson, Sterling C. Johnson, Erik K. Kastman, Kristopher J. Kosmatka, T. Mark Beasley, David B. Allison, Christina Cruzen, Heather A. Simmons, Joseph W. Kemnitz, and Richard Weindruch
Science 10 July 2009: 201-204.

Journal pre-amble: Age-associated death and onset of pathologies are delayed by controlled caloric restriction, thus prolonging life span.

Abstract
Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species. Evidence that mammalian longevity could be increased emerged in 1935 in a rodent study showing that caloric restriction (CR), without malnutrition, extended average and maximum life span and delayed the onset of age-associated pathologies (1). It was not until the 1990s that CR became widely viewed as a scientific model that could provide insights into the retardation of the aging process (2) and thereby identify underlying mechanisms of aging (3). The inverse relationship between calorie intake and increase in life span in mice suggests a role for regulators of energy metabolism in the mechanism of CR. Accordingly, CR-induced metabolic reprogramming may be a key event in the mechanism of life span extension (4). Studies in yeast, worms, flies, and mice point to a role for nutrient-responsive signaling molecules, including SIRT1, mTOR, and PGC-1, in aging and CR (5). The relevance of these findings for human aging depends on the conservation of the effects of CR on aging in primates.

Edited by Michael, 10 July 2009 - 08:53 PM.
Moved to Member's Area for ©

[Shannon Vyff]

There will be more results from this study, it could be up to 15 years till the last CR'd rhesus dies. I was happy to hear from my husband that CR was in the news, as he reads CNN and major news sites daily--that this study is making the rounds on AP is wonderful. The New York Times article along will likely increase sales of CR books and hits on CR sites

[brokenportal]

I saw this at the newspaper stand today. I forget which one I saw it on the cover of.

This is another great example of the little successes that are piling up and getting ready to give rise to wider, more in depth, coverage of the whole cause.

[Matt]

Nice new pic released of another two monkeys that are asme age but as usual, CR one looks younger and still has a nice coat

http://img.photobuck.../cr_monkeys.jpg

and a new pic of canto and owen 2 + years later (high res)

http://img.photobuck...sComparison.jpg

Edited by Matt, 16 July 2009 - 01:32 AM.

[kismet]

I think worrying about running the study another decade before publishing is verging on anal retentive. Do they really think that some quirk of primate biology will have the CR group suddenly drop dead in the near future?

Unfortunately, that could very well happen. At least it could happen with your run-off-the-mill intervention. We have seen dozens of stubstances that decreased early life mortality and increased average life span in rodents just to see them head towards 0% survival as quickly as the placebo group. Species maximum life span is a tough enemy and such studies get interesting only in the end. First, they have to prove that it will extend maximal life span. Going off the rodent data most people expect it to happen (proof is still required, we're scientists and pretty careful people after all), but even more important is to find out about the magnitude of the effect. Does it work better or worse in primates? Are there diminishing returns? Does it slow all kinds of age-related pathologies in primates?

[niner]

Unfortunately, that could very well happen. At least it could happen with your run-off-the-mill intervention. We have seen dozens of stubstances that decreased early life mortality and increased average life span in rodents just to see them head towards 0% survival as quickly as the placebo group. Species maximum life span is a tough enemy and such studies get interesting only in the end. First, they have to prove that it will extend maximal life span. Going off the rodent data most people expect it to happen (proof is still required, we're scientists and pretty careful people after all), but even more important is to find out about the magnitude of the effect. Does it work better or worse in primates? Are there diminishing returns? Does it slow all kinds of age-related pathologies in primates?

These are very good points, and I wouldn't advise stopping the study now. I do think it's reasonable to publish now, and again later as they have statistically significant results. It might be different if CR hadn't already been successfully applied to numerous other species.

[Mind]

seems like a very grey issue.

it does kind of bother me a little that the 7 ad lib and 9 CR monkeys dying were excluded. i guess i'd want to know specifically how those monkeys died and if all the others still living experienced the same set of circumstances.

i think you need to look at the data in its entirety, and not allow for the researcher's discretion in deleting deaths from the study. it can be a slippery slope. however, i think you also have to look at the whole set of biological facts, including bloodwork/physical fitness before death and not just the death as a single datapoint.

this issue sort of brings us back the past discussion from the thread re: 'slightly overweight people living longer than thin people." if you get an injury, become immobilized, and have enough body weight/mass so that you can survive and not starve to death until you recover, than maybe the ad lib diet is better than CR.

We live in the real world, not in a sterile lab environment. If you go on CR, exhibit great telomere lengths, but you are frail/fragile and not as durable a person then it may be a trade-off in some regard.

I couldn't have said it better myself. The accidental deaths DO MATTER. Frailty leads to immobility which leads to death (in humans). There is also the curious matter that slightly pudgy humans live longer - which again might have to do with the fact that they have a reserve energy store to help them make it through a time of injury or infection. Still, this is a great result for lab/controlled longevity. Barring injuries and infection, CR "takes the cake" for retarding most aging pathways.

[Matt]

I couldn't have said it better myself. The accidental deaths DO MATTER. Frailty leads to immobility which leads to death (in humans)

Although I believe the majority (if not all) deaths from accidents occured very early on in the study. Will have to try and confirm this. Most of the issues with anesthesia, gastric bloat, and accidents (head trauma i believe) were able to be more controlled further into the study.

Accident is an accident, it doesn't tell you about if or not aging is slowed down. It has to be factored out. Maybe this comes down to a personal decision on whcih survival curve / data you want to take notice of. For me i'm happy taking more notice of the age related one. Anesthesia also, i believe the monkeys get put under 1-2 times a year. This should definitely be excluded. For me these seem perfectly reasonable and i'm happy they supplied both data.

Edited by Matt, 11 July 2009 - 02:39 AM.

[Matt]

Just finished off a blog post on the primate study if anyone interested in checking it out http://matts-cr.blogspot.com/

[Sillewater]

Calorie restrictive eating for longer life? The story we didn’t hear in the news

This blog post brought up the issue prophet mentioned. It also mentioned that the control monkeys were overfed by 20% compared to normal.

Since 1989, we have been studying the effects of a moderate (30%) adult-onset dietary restriction (DR) in a nonhuman primate model. We chose a rhesus monkey (Macaca mulatta) model… The effects of aging and DR are being analyzed longitudinally in adult male rhesus monkeys, ranging in age from 8 to 14 years (average 9.3 years) at study onset… The 30 rhesus monkeys used in this study were born at and have lived their entire lives at the Wisconsin National Primate Research Center… [In 1994, an additional 30 females and 16 males were added to the study.] Prior to the start of the study, animals were monitored for individual baseline food intakes of a purified diet (10% fat, 15% protein) for 3 months. Animals were then randomized to either Control or Calorie Restricted groups based on their baseline food intakes. Food allotments for the CR animals were then reduced by 10% per month for 3 months to reach the intended 30% DR. Control animals were fed 20% more than their average daily intake…

It also mentioned Aubrey de Grey's criticism of CR. I remember there being a response from Michael to Aubrey's criticism, could someone point me in the right direction.

It's great that this study is being done so that the genetic expression could maybe be mimicked by pharmaceuticals but in real life I would rather not try caloric restriction.

[tunt01]

imo, her article is excessively critical.

She seems to have this very narrow, negative agenda at the outset. "This is all bad." There are clearly some positives associated with CR, as evidenced by the biomarkers. I've no idea how this one paper can find "aggressive behavior" in CR practitioners, when they exhibit better vascular biomarkers. Also, I thought most CR practitioners had slightly lower testosterone.

If I can recall, MR's response to Aubrey was something along the lines of: "Aubrey has no data. CR has practical data behind it. Show me the data otherwise."

It may very well come down to the fact that the population used in the primate study was too low to generate a statistically significant result. It's unfortunate for now. It may eventually generate one later. I'm sure these guys live and breathe this research as their life. When you suffer the consequences of a 15-20 year experiment that wasn't set up quite right in the first place (1. not enough animals and 2. giving 20% extra calories to the 'control' group), it's a shame.

I'm sure if scientists proposed a diet with 2500 calories per day but a higher level of exercise (a normal amount of calories, but burned off through exercise), people might not look at it as an oddity.

There are also very significant epigenetic components involved in any diet. From the womb through the first two years of life, we are all programmed metabolically. It may explain why CR does not agree with some people. I think the concept of LifeGen and the gene chip assay, is actually quite promising.

I'd really like to see a DEXA scan of these primates, to see if CR is depriving the monkeys from bone over the years. If you are losing bone mass with CR, then your risk of falling and being injured (breaking a hip, etc.) is much higher.

Edited by prophets, 15 July 2009 - 11:32 AM.

[Matt]

This blog post brought up the issue prophet mentioned. It also mentioned that the control monkeys were overfed by 20% compared to normal.

No I don't believe this is true, the ad lib intake was also not 'true' ad lib and they had their food taken away from them. As with proctols in other animals I believe the control group were also restricted to try and prevent obesity.

It also mentioned Aubrey de Grey's criticism of CR. I remember there being a response from Michael to Aubrey's criticism, could someone point me in the right direction.

Yea I can send it to you if you want

She also says in her blog

The non-aging-related causes of death included monkeys who died while taking blood samples under anesthesia, from injuries or from infections, such as gastritis and endometriosis.

The monkeys did not die from infections or gastritis. They mostly died for PREVENTABLE causes if more care was taken. i.e Not overcooking batch of food and killing the monkeys from gastric bloat, duh.

and look how the way she words this one'

As the supplemental data explains, 16 deaths from “non-age-associated causes were censored and their age of death used as the time variable in the regression.

She words it so the average reader without looking more into it would probably assume these 16 deaths were all from the CR group.

she goes on to say

but they could realistically be adverse effects of prolonged calorie restrictions on the animals’ health, their immune system, ability to handle stress, physical agility, cognition or behavior.

Well no there is no data that supports immune systems were weakened in monkeys, they never died from infections, CR animals usually are able to withstand greater stress, the CR monkeys were reported to be in better shape physically, as you can see by their posture and the way they move on video, and in terms of cognition, it seems the CR monkeys are doing better. Not much behaviour differences were noted in the papers on the primates.

she goes on to say

the control animals were overfed 20% more than their usual diet, while the CR monkeys’ diets were adjusted to keep them about 30% less than the control monkeys.

I think this is rubbish, the control group were not as I recall fed 20% more than their ad lib intake, she doesn't supply any references for this, then she assumes that the CR monkeys were fed 10% less to achieve a 30% reduction in calories? Each CR monkey had its baseline intake calculated and reduced by 10% each month until reaching 30% below its normal calorie intake.

Edited by Matt, 15 July 2009 - 01:53 PM.

[Matt]

Email from someone on the CR lists about the Junkfoodscience blog

"As I suspected, Ms. Szwarc writes for a lobbying firm that denies global warming, etc and is funded by McDonalds, among other conglomerates. (If you know who is paying for an opinion, you can generally figure out what it will be.)

http://www.sourcewat...Central_Station

She is identified here as an "obesity crank" and for misinterpreting studies and other sophistry here:

http://scienceblogs....ng_pro.php#more "

Edited by Matt, 15 July 2009 - 02:39 PM.

[tunt01]

doesn't surprise me.

i noticed comments were turned off on her blog and found that to be quite odd.


EDIT:

I just checked the same sources. That person is wrong. She used to be a contributor to a republican-leaning lobbying group. She also contributed to a libertarian one.

She claims her blog is independent, receives no outside funding and it is labeled as such on the side of it. She accepts donations from readers only, not corporations.

read this: http://junkfoodscien...eated-this.html

she's won a few awards (whatever that means), and brandishes this Med-Blogger code of ethics http://medbloggercode.com/the-code/ as a testament to her impartiality.

I don't think her analysis is spot on, but doesn't seem conflicted, as this CR Society person would suggest.

Edited by prophets, 15 July 2009 - 05:11 PM.

[Sillewater]

I don't agree with Mark Hoofnagle analysis, especially since he criticizes Gary Taubes for his theories and leaves his faults to nitpicking,which Gary Taubes is very good at , which is why I think he figured out what he did.

Thanks Matt for the analysis. I saw the paper in the members section posted by Michael, so I agree with your points; she does make it seem worse than it actually was, many of the deaths seemed preventable (and great blog post btw).

However I do not think her she blogged about CR in that way because she's sponsored by McDonalds.

I mean the researchers for the CR Monkey study also have a company:

LifeGen was co-founded in November 2000 by Drs. Richard Weindruch and Tomas A. Prolla, professors at the University of Wisconsin-Madison and leaders in the fields of gerontology and genetics.

So maybe they were trying to put a positive spin on their results.

However I do trust in Michael's analysis of the situation and I just read his critique and its true that Aubrey's stance may be unsubstantiated.

I just hope that a CR mimic that works will come out soon

[kismet]

I think this is rubbish, the control group were not as I recall fed 20% more than their ad lib intake, she doesn't supply any references for this, then she assumes that the CR monkeys were fed 10% less to achieve a 30% reduction in calories? Each CR monkey had its baseline intake calculated and reduced by 10% each month until reaching 30% below its normal calorie intake.

MR has pointed out that the ad lib group is actually eating less and less as time goes on...

No matter how ridiculously you twist this result, it's still absolutely astonishing and positive proof in favour of CR.

i think you need to look at the data in its entirety, and not allow for the researcher's discretion in deleting deaths from the study. it can be a slippery slope. however, i think you also have to look at the whole set of biological facts, including bloodwork/physical fitness before death and not just the death as a single datapoint.

this issue sort of brings us back the past discussion from the thread re: 'slightly overweight people living longer than thin people." if you get an injury, become immobilized, and have enough body weight/mass so that you can survive and not starve to death until you recover, than maybe the ad lib diet is better than CR.

I'm sure it's not a slippery slope and there was oversight from their peers. If you ask the authors, they may even provide the data.

We live in the real world, not in a sterile lab environment. If you go on CR, exhibit great telomere lengths, but you are frail/fragile and not as durable a person then it may be a trade-off in some regard.

No, we don't. I just don't see this argument. Most of the time we do live in a cage (or cage-like and safe environment). Additionally, we should be careful about the use of "fragility", which often means sarcopenia & osteporosis, which clearly was prevented by CR (at least sarcopenia was, I thought age-related osteoporosis too?)

Edited by kismet, 15 July 2009 - 06:27 PM.

[Matt]

MR has pointed out that the ad lib group is actually eating less and less as time goes on...

I provided some information and a graph on the food intake over time from the researchers which was presented a little while ago, video is also available on here (imminst) and my blog. The Ricki who leads the study goes through the data we have the moment. http://matts-cr.blog...nkey-study.html See food intake.

[kismet]

Good post Matt. I must admit her spin is funny as hell. "That's not how science works". Nope, you're doing it wrong, Sandy. How can any sane person twist reduced morbidity + reduced adjusted mortality + a trend towards reduced overall mortality to be something bad?

But I'm not sure if she isn't right on one point? That old paper in fact states "C[ontrol] animals were fed 20% more than their average daily intake to assure ad libitum access to food for 6–8 hours per day." http://biomed.geront...t/full/63/6/556
I'm just not sure what it means. It could mean they were over-fed by 20% or they were offered 20% more food so that they could eat ad lib. Both could potentially result in overfeeding (assuming ad lib monkeys tend to indulge in food like some humans and rodents..), but the former would be much worse than the latter. Which one is it? More likely than not, it's her spin, considering how she left out the second part of that sentence.
It seems that according to MR both groups consumed too many calories to be a good test of *real* life-extending CR. Then again, this makes the results even more promising.

EDIT:
Her post demonstrates breath taking inanity, totally and completely misrepresenting the CR literature. The usual drivel like CR is not universal or CR does not extend life span of wild-type mice. Her analysis is so shallow as not to be even deserving of some not-so-respectful insolence (as ORAC would put it). Just in case anyone believes this. Yep, CR is not universal, it merely works in 90%+ of all model organisms, including the most important and long-lived ones. There is this infamous study showing that CR does not increase average or max (?) life span of wild-type mice IIRC. For one thing, it's riddled wit serious problems and on the other hand it actually showed CR to be benefical: the cancer incidence was drastically reduced and most of the longest-lived animals were from the CR group.

Edited by kismet, 15 July 2009 - 08:44 PM.

[Matt]

"animals were fed 20% more than their average daily intake to assure ad libitum access to food for 6–8 hours per day"

Okay, so the confusion here seems to be that people are thinking that they ad lib animals are consuming ALL their food, no they are not. The food at the end of the day is taken from their cages an counted to see what they've eaten and this goes for both groups (hence why we have the food intake graph. The graph I showed you shows that the animals on CR are eating 20-30% below the control group, but all 3 CR groups are eating 30% below their OWN baseline intake which was counted before entry into the study for 3-6 months.

It seems that according to MR both groups consumed too many calories to be a good test of *real* life-extending CR. Then again, this makes the results even more promising.

Yeah probably. Though if you were in charge of a 30 year study would you try even more extreme CR right off? And is it taking too much of a risk given the length and cost of it.

Attached Files

•  foodintake.jpg   30.42KB   27 downloads

Edited by Matt, 15 July 2009 - 08:41 PM.

[kismet]

Is there any HGH/IGF axis data on those primates available? After all, Dr. Fontana (and some of our members considering low protein diets) may not be able to sleep at night, as long as they don't know whether low IGF-1 levels are necessary for CR to work.

Edited by kismet, 15 July 2009 - 09:00 PM.

[Matt]

The survival curve though looks pretty good right now, considering the average lifespan in captivity for a rhesus monkey is 25-27 years. Even the ad lib group seems to be doing quite well. To get human equivalent age they say you should just x3 the primate age to get human equivalent.

Is there any HGH/IGF axis data on those primates available? After all, Dr. Fontana (and some of our members considering low protein diets) may not be able to sleep at night as long as they don't know whether low IGF-1 levels are necessary for CR to work...

They are eating low protein so its likely their IGF-1 is lower, I think there s a paper showing this, give me 5 min to find it.

Edited by Matt, 15 July 2009 - 09:02 PM.

[kismet]

Let me continue to destroy Sandy's article while you search.
Just enjoy:
"In other words, making the food more “nutrient-dense” as claimed by CR advocates, doesn’t make caloric restrictions more healthful or lessen certain adverse effects."
Wow, if this misinformation wasn't so friggin' dangerous it would be fun to point it out, but that statement is not even wrong. I never checked the literature myself, but MR has emphasised that CR researchers have demonstrated the exact opposite again and again. Furthermore, as a matter of fact, most CR diets will end up very low if not severely deficient in some nutrients without the guidance of Cron-o-meter (at least that's what I've seen and been told by people) -- not just because they're low in calories, but because they're also restrictive when it comes to some other foods. I'm sure she's disregarding the RDAs for a reason and malnutrition won't kill us, now will it?

"Increasing numbers of professionals are critical of the CR movement for ignoring whole classes of negative outcomes resulting from chronic hunger, such as on behavioral and cognitive function and quality of life, including sociability, curiosity and emotionality."
...
"Nor is there evidence that vitamin-enrichment of caloric restrictive diets will reduce the depression, decreased sociability and narrowed scope of interests seen in semi-starvation."
Yeah, we know you are oblivious of the science by now.

Ho-hum: http://www.imminst.o...&...st&p=260625

Can we sue her for libel?

EDIT:
Does anyone notice the irony, she's quoting Aubrey's weathermen hypothesis, because it suits her case, but I'm wondering why she doesn't mention Aubrey's "only cancer matters" hypothesis. Maybe because it disagrees with the point she's trying to make?
“For example, early studies indicated that DNA repair capacity was higher in longer-lived mammals, arguing that DNA repair was a factor in aging, [yeah, I know the point she's making borders on a non sequitur, but she still employs this as an argument that CR may not work... just like antioxidants! maybe with the small difference that antioxidants even fail in model organsims... while CR doesn't]"

No, wait, that's not her point at all. But the comparison with antioxidants is still stupid, because they fail in model organisms while CR doesn't.

Edited by kismet, 15 July 2009 - 09:26 PM.