21 replies to this topic

[Brett Black]

I think there's a very strong case to be made that almost all humans currently practicing caloric restriction are doing so in a way that fundamentally and significantly differs from how caloric restriction is implemented in and affects rodents. Here is my argument:


The overwhelming majority of caloric restriction(CR) experiments in rodents, whether studying lifespan, longevity or health effects, involve rodents on CR being served a single ration of food per day(with a few exceptions, which are addressed in detail below.)

This delivery of a single ration of food per day is usually used in CR'ed animals simply because it is the easiest way to implement a calorie-restricted diet. All the food for the day is measured out and then delivered to the feeding area of the animal all at once, which is much easier than delivering multiple precisely measured batches of food throughout the day.

In comparison, the "control" ad-libitum(free-feeding) rodents in these experiments usually have a constant supply of food available to them.

It is sparsely mentioned or dealt with in the CR literature, but this difference in feeding regimes is known to result in dramatic differences in feeding behaviours between CR'ed and ad-libitum fed rodents.

Ad-libitum rodents engage in a natural "nibbling" feeding pattern, eating many meals throughout the day. Ad-libitum fed rats rarely go for longer than 3 or 4 hours at at time without feeding(1) and ad-libitum mice rarely go for longer than 1 hour without feeding(11.)

On the other hand, rodents subjected to CR gorge on their single food ration and finish it all in a very short period of time(2). This feeding pattern, unlike in the ad-libitum animals, thus results in long periods of complete food deprivation(fasting) in the CR'ed rodents until the next day's meal is supplied to them.

It has been shown that 50% of rats on a conventional CR feeding regime finish their entire daily food ration within 3.5 hours, and 90% of rats finish it all in under 5 hours(2). This means that 50% of CR'ed rats are going for more than 20.5 hours per day without any food at all, and 90% of the CR'ed rats are going for more than 19 hours without any food per day.

CR'ed mice eat their entire food ration within just an hour(11) and are thus subjected to a full 23 hours without food per day with conventional CR feeding regimes.

This major difference in fasting duration between ad-libitum and CR rodents results in a raft of very significant physiological differences(3.) When subjected to only 16 hours without food(considerably less than that experienced by the average CR'ed rodent), rats lose an average of 6.9% body weight, their serum glucose concentrations drop by an average of 34.9%, triglycerides drop by 48.4% and cholesterol drops by 21.7%(3). CR'ed rats deplete their glycogen stores during the period of fasting between meals and transition into a daily state of ketosis, as well as experiencing hypothermia during this period(11). Mice rapidly switch to fatty acid oxidation(and ketosis) for fuel after just 6 hours without food(12).

The time scale for many aspects of rodent metabolism is radically different to that of humans, so what seems like a short period of time for a human may actually represent a very long period by rodent standards.

How might this translate and scale into human terms? Here are some comparisons: when subjected to complete food deprivation(fasting) it takes humans about 10 days to lose 10% body weigh(6), it takes rats about 24 hours to lose 10% body weight(3) and it takes mice less than 24 hours to lose 10% body weight(7).

Non-obese humans can survive about 60 days of complete starvation(8), rats can survive about 10 days of starvation(9), mice can only survive about 6 days of starvation(10).

By these measures, which arguably seem very relevant to the matters being discussed, there is from a 6:1 to 10:1 ratio between humans and rodents in terms of speed and duration of these particular metabolic processes.

Taking into consideration these ratios, along with the known feeding patterns of rodents on CR, it could be suggested that the approximately 20 hours of fasting that regular CR'ed rodents experience on a daily basis, is equivalent to 120 to 200 hours of fasting for a human(5 to 8 days.) The approximately 4 hours of food gorging in CR'ed rodents might be the equivalent of a human eating about a normal week's worth of food within a period of one to two days. For a human male of 70kg, the daily weight-cycling of about 7% that rodents experience on CR would be equivalent to continuously rapidly losing and then gaining 5kg of body weight.

Could these long periods of fasting, short periods of food gorging and the associated major impacts on physiology be the source of some or all of the beneficial effects seen in CR rodent experiments?

So far, there have been a very small number of studies that have attempted to answer these questions. These studies reported that the life-extending properties of CR still occur when more frequent feeding regimes are used in CR'ed rodents. But I think there are some real problems with these studies.

The two studies(that I am aware of) that increased feeding frequency and reduced fasting duration the most, still left rats with a daily 16 hour gap between food rations(4), and left mice for a 12 hour daily gap between food rations(5). As noted above, ad libitum rats normally experience a maximum of just 3 to 4 hours between meals, and ad libitum mice just 1 hour gap.

Were these studies sufficient to rule out the effects of long periods of fasting? As shown above, even just 16 hours of food deprivation in rats results in very significant physiological effects. Mice likely experience even quicker alteration in physiology due to food deprivation, such that 12 hours without food may still be a significant period for them to go without food. These rodents were quite likely still undergoing ketosis, for instance.

To give a comparison: using the best-case scenario, based on the feeding regimes used in the small number of studies that attempted to limit the periods between feedings, and the human:rodent metabolic ratios described above, a human-scaled equivalent feeding regime would still lead to somewhere between about 72 and 160 hours between meals. That's a minimum of three days without eating in human terms, and that's given the best case scenario currently available from studies into rodents.

So where does this leave human caloric restriction? Should humans be engaging in multi-day fasts, interspersed with short periods of food gorging, if they want to mimic the rodent experiments? Others have suggested that a regime like this may in fact be necessary to reproduce the effects seen in rodents(13). Several tantalizing hypotheses and pieces of evidence lend support for this view. Some of the most popular and promising theories explaining the effects of CR, including modulation of autophagy, apoptosis, lipolysis and protein turnover, seem likely to require longer-term fasting in humans to be effectively activated(14,15.) Changes in gene expression have also shown that fasting seems to regulate the genes that respond to CR(16.)

In short, I believe that there is a very strong argument to be made, that the conventional caloric restriction regimes that are currently used by most human CR practitioners(ie eating at least one or more meals every day or two), are not suitably replicating the regimes or many of the major physiological effects of CR seen and used in any CR rodent studies to date.

-

(1) "Meal patterns in the genetically obese Zucker rat: a reexamination"
Castonguay TW, Upton DE, Leung PM, Stern JS. PMID: 7100292

(2) "Methods for Inducing and Monitoring Liver Autophagy Relative to Aging and Antiaging Caloric Restriction in Rats"
Donati A, Cavallini G, Bergamini E. PMID: 19200897

(3) "Effect of fasting duration on clinical pathology results in Wistar rats"
Kale VP, Joshi GS, Gohil PB, Jain MR. PMID: 19351329

(4) "Temporal Pattern of Food Intake Not a Factor in the Retardation of Aging Processes by Dietary Restriction"
Masoro EJ, Shimokawa I, Higami Y, McMahan CA, Yu BP. PMID: 7814779

(5) "Meal-timing, circadian rhythms and life span of mice"
Nelson W, Halberg F. PMID: 3794831

(6) "Metabolic Aspects of Acute Starvation in Normal Humans (10 Days)"
Consolazio CF, Matoush LO, Johnson HL, Nelson RA, Krzywicki HJ - PMID: 6036255

(7) "Acute Starvation Protects Mice Against Listeria monocytogenes"
Wing EJ, Young JB. - PMID: 6772566

(8) "Fasting - the ultimate diet?"
Johnstone AM. PMID: 17444963

(9) "Factors influencing survival of rats in fasting; metabolic rate and body weight loss"
RIXON RH, STEVENSON JA. PMID: 13411211

(10) "Response of germfree, conventional, conventionalized and E. coli monocontaminated mice to starvation"
Tennant B, Malm OJ, Horowitz RE, Levenson SM. PMID: 4866341

(11) "Effect of chronic caloric restriction on physiological variables related to energy metabolism in the male Fischer 344 rat"
Duffy PH, Feuers RJ, Leakey JA, Nakamura K, Turturro A, Hart RW. PMID: 2661930

(12) "Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates"
Bruss MD, Khambatta CF, Ruby MA, Aggarwal I, Hellerstein MK. PMID: 19887594

(13) "Caloric restriction in C57BL/6J mice mimics therapeutic fasting in humans"
Mahoney LB, Denny CA, Seyfried TN. PMID: 16709251

(14) "Proteolytic and lipolytic responses to starvation"
Finn PF, Dice JF. PMID: 16815497

(15) "The role of autophagy in aging: its essential part in the anti-aging mechanism of caloric restriction"
Bergamini E, Cavallini G, Donati A, Gori Z. PMID: 16709251

(16) "Starvation response in mouse liver shows strong correlation with life-span-prolonging processes"
Bauer M, Hamm AC, Bonaus M, Jacob A, Jaekel J, Schorle H, Pankratz MJ, Katzenberger JD. PMID: 14762175

[leha]

That's a fascinating perspective. But where do studies like this one fit in?

Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age.

The adult mice in the study that were methionine restricted ate ad libitum otherwise and still came out with lifespan extension.

Also, what about alpha-MUPA mice, which eat ad libitum and still receive the benefits of caloric restriction due to their genetically-suppressed appetites? For them, timing of meals is completely voluntary.

Finally, the meal timing of one of the groups in the study you cite, "Meal-timing, circadian rhythms and life span of mice," was 6 meals at 2-hr intervals over the course of the night (12hrs). Since mice are nocturnal and prefer to sleep during the day, is this really a harsh fasting regimen? One of my pet rats ate pretty much like that on her ad libitum diet (the other one was pretty piggy).

Edited by leha, 14 November 2010 - 08:56 AM.

[Guest]

In short, I believe that there is a very strong argument to be made, that the conventional caloric restriction regimes that are currently used by most human CR practitioners(ie eating at least one or more meals every day or two), are not suitably replicating the regimes or many of the major physiological effects of CR seen and used in any CR rodent studies to date.

Interesting. Do you also know the feeding shemes they employed in CR-ed dogs and cats? Also it would be interesting to know wheter the Squirrel and Rhesus Monkeys are kind of 20-hours a day fasting.

[Matt]

All monkeys in the wisconsin rhesus monkey study have access to food for 8 hours a day.
http://videos.med.wisc.edu/videos/8118

Edited by Matt, 15 November 2010 - 10:39 PM.

[Forever21]

So for CR to work, we should eat for 2 days only and fast for the next 5-8 days?

[Matt]

No! All the indications so far (from extensive tests in humans and monkeys) is that humans respond in the same way to calorie restriction as does rodents, there is no need to change the way we practice CR. It's just the overall calories that matters, and possibly protein level to lower IGF-1. I watched the presentation by Paul Mcglothin and he seems to be suggesting that there is an optimal way to do CR which could give us the benefits of possibly a more severe CR, simply because we have more control over the quality of our diet and other factors in humans to influence various longevity pathways. Well done to the person who wrote this, but I think its way off mark.

[xEva]

Great job, Brett! And thank you for all those references.

No! All the indications so far (from extensive tests in humans and monkeys) is that humans respond in the same way to calorie restriction as does rodents, there is no need to change the way we practice CR

You guys are engaged in wishful thinking, and the reason is, you know nothing about the metabolism of starvation. It's a scary word for you, and that's why you don't want to know anything about it. But the fact is --if you understand anything about metabolism-- those mice/rats are starving regularly, and that's why they get those dramatic life extension benefits. Simply eating less, the way you do it now, will buy you some 10-15 years of human life. Compared to ad lib humans who get 70-80 years, right?

You have to appreciate the fact that absolutely everything alive on this planet, from yeast to worms to mice and humans, evolved to undergo frequent periods of starvation. Frequent famine is the norm. Think about it.

When you take your time to study starvation, you will appreciate the fact that evolution relies on it to repair the damage caused by daily living. There is a genetic program that kicks in when you enter the ketosis of starvation. You cannot fake it with any drug or supplement, because the homeostasis is set around a vastly different metabolic point. The chemistry is different and it all works in concert. But to appreciate this, you have to get some knowledge... and you can't expect to get it from a post..

[Guest]

When you take your time to study starvation, you will appreciate the fact that evolution relies on it to repair the damage caused by daily living. There is a genetic program that kicks in when you enter the ketosis of starvation. You cannot fake it with any drug or supplement, because the homeostasis is set around a vastly different metabolic point. The chemistry is different and it all works in concert. But to appreciate this, you have to get some knowledge... and you can't expect to get it from a post..

You already have proven yourselfs to have such knowledge, haven't you... (rolleyez)


The point was, that yes, mice have different metabolic rates and yes, there might be a lack of comparative studies investigating feeding shemes (so whether mice on a calory restricted frequent-meals diet show no caloric restriction effect as Brett seems to be convinced). But caloric restriction works on a broad range of animals with vastly different metabolic features. Is there a metabolic connection to starvation? Maybe, as CRONies show similar bio markers as people on fasts. However, just because animals (not just mice) are limited to few meals a day in CR experiments doesn't mean that its the feeding sheme. Contrary, every evidence available points to the fact, that its the calories and not the feeding sheme; although indepth investigations are mostly available for human biomarkers.

Just because researchers out of practical considerations use a certain feeding sheme doesn't allow the conclusion that the effect measured is not based on calories but the eating timeframe. To draw that conclusion you have to provide at least one single study using an alternative feeding sheme showing no CR-effect.

[xEva]

The point I'm trying to make, the one people here have difficulty understanding --again, only because you did not take time to understand the metabolism of starvation-- is the difference between CR, when you eat sparingly, and starvation (bad word, I know, but..) when for a stretch of time you don't eat at all. The good analogy would be "repairs and maintenance", say, of a bridge. CR is like having daily upkeep, fixing things on a regular basis.. and everyone will agree that whatever is the system, be it mechanical or biological, if you maintain it well on a regular basis, it will last longer. You can make a lot of repairs on a bridge, even if you close one lane at a time, it is still operational. CR is like this. But still, even with a good maintenance, you will agree, eventually, some structural damage will accumulate and in order to fix it, you'd have to close the shop, so to speak. That's starvation.

Now, I can't convince you of this, because in order to do this, I'd have to inform you of all those things that go on metabolically during starvation, and that's a lot of material to cover (rolleyez) Here I can only remind you that the genetic repair program that kicks in during starvation is very ancient one, preserved in all species living today, and that's what allows us to study it on different animal models (ex. sirtuins).

Returning to mice and rats and how they compare metabolically to humans, the fact is that those CR'd animals starve regularly. They are in deep ketosis of starvation after less than 24h already. It is NOT comparable to humans on CR. There is a difference, and it is in degree of ketosis and => chemistry => genetic programs that are activated..

[kismet]

From what I see this the same argument (no offense to the OP) that MR destroyed not too long ago. Please see:
http://www.imminst.o...970#entry431970

Edit:
I see that you address some of the objections. Good! Some additional questions:

So, do you know whether Nelson's ad lib rats, not just your "normal rodent" but the actual controls that matter, also ate every 3-4 hours? Wouldn't "pattern feeding" approximate their feeding regimen well enough?

Also, CR regimens that at least *tried* to replicate the natural pattern, which if done correctly would in your view negate the CR benefits, must show a *trend* for worse outcomes. Do they? (i.e. Nelson & Masoro)

Then there is the translatability of CR to other mammals with much slower weight-loss? How do you reconcile this?

Why do EOD regimens fail in rodents? (I can guess the answer to that one, but there are still points worth discussing)

What about hormonal markers? CRONies may show altered thyroid metabolism* which is consistent with increased longevity despite doing "wrong" CR?

Mechanistically, why would such a pervasive mechanism as CR ignore thermodynamics? Only the long term calorie intake is a true marker of starvation; why should fluctuations evoke such a response? A CR response to anything else does not seem adaptive, so why would it be selected for? This does not seem consistent with current hypotheses of CR, e.g. the idea of "live to breed another day".

Can you find backing for your idea in human studies? Can you cite specific examples? (IIRC IF has no or only modest metabolic benefits in humans, but my recolection may be off)

*I forgot if this is anecdotal or has backing from one of the CR cohorts

Edited by kismet, 18 November 2010 - 09:42 PM.

[Esoparagon]

Based on your 6:1 ratio the ad-libitum rats are waiting 24 hours to eat a meal when translated to human terms. I don't think any ad-libitum humans eat this way. Are you sure the mice are going into ketosis with a days worth of glucose in their bodies? Normal rats who just had a small meal might enter ketosis after 6 hours because it only has a small amount of food to digest before it must switch to glycogen and fat stores but a mouse that has just gorged itself should have glucose being released from the digesting food. I think there are some leaps of logic in your argument.

Edited by Esoparagon, 19 November 2010 - 01:10 PM.

[nowayout]

Why don't traditional desert dwellers like the Kalahari Bushmen, who had/have a feast or famine low-calorie paleo diet, live long? They tend to look ancient at the age of 40.

[xEva]

From what I see this the same argument (no offense to the OP) that MR destroyed not too long ago. Please see:
http://www.imminst.o...970#entry431970

Destroyed? How so? By dismissing the research that showed that 40% CR'd mouse has the same metabolic markers as a human starving for a week? He only showed that he does not understand ketosis, does not understand the metabolism of starvation --I'm tired of repeating this-- nor he understands how it all relates to activation of the ancient genetic repair programs, the ones we are after with substances like resveratrol.

It is impossible to convince someone of something of which they have not even basic knowledge.

So, do you know whether Nelson's ad lib rats, not just your "normal rodent" but the actual controls that matter, also ate every 3-4 hours? Wouldn't "pattern feeding" approximate their feeding regimen well enough?

Also, CR regimens that at least *tried* to replicate the natural pattern, which if done correctly would in your view negate the CR benefits, must show a *trend* for worse outcomes. Do they? (i.e. Nelson & Masoro)

-??.

Then there is the translatability of CR to other mammals with much slower weight-loss? How do you reconcile this?

You miss the point entirely. No one argues that CR has no benefit. The argument is that therapeutic starvation has far more reaching benefits than CR, exactly because only then we enter deep ketosis that kicks in all those repair programs we are after.

Why do EOD regimens fail in rodents? (I can guess the answer to that one, but there are still points worth discussing)

What about hormonal markers? CRONies may show altered thyroid metabolism* which is consistent with increased longevity despite doing "wrong" CR?

Mechanistically, why would such a pervasive mechanism as CR ignore thermodynamics? Only the long term calorie intake is a true marker of starvation; why should fluctuations evoke such a response? A CR response to anything else does not seem adaptive, so why would it be selected for? This does not seem consistent with current hypotheses of CR, e.g. the idea of "live to breed another day".

Can you find backing for your idea in human studies? Can you cite specific examples? (IIRC IF has no or only modest metabolic benefits in humans, but my recolection may be off)

*I forgot if this is anecdotal or has backing from one of the CR cohorts

-?? ... all this only shows how little you understand subject at hand. I wash my hands..

And the same goes to the following 2-3 posts. Sorry guys, I have no patience for this. I'm not an educator type. Besides, I get no points for convincing you that fasting sometimes is good for you. But there are intelligent and knowledgeable people here and they do not require all this massaging

[Forever21]

So what is the practical / optimal / best way of doing this?

a) IF alone
b) CR + IF
c) CR + MR + IF
d) other (what?)

[Guest]

Destroyed? How so? By dismissing the research that showed that 40% CR'd mouse has the same metabolic markers as a human starving for a week? He only showed that he does not understand ketosis, does not understand the metabolism of starvation --I'm tired of repeating this-- nor he understands how it all relates to activation of the ancient genetic repair programs, the ones we are after with substances like resveratrol.

YOU are dismissing my reply to the past thread. Basically the paper you cite is flawed in the way, that the researches never actually compared their results to actual available human CRON data. The human CR-data of the Fontana group is similarly compatible with the rodent data as the arbitrary mix of various starvation studies they use. If any this is an argument in favour of CRON. Please respond... And what you mean with "understand" - could you enlight us with your superior understanding (meaning some arguments instead of general allegations)? And pelase do not as previously refer to the russian women who claims to live of zero kcal for month while doing exhaustive sport daily.

[xEva]

YOU are dismissing my reply to the past thread. Basically the paper you cite is flawed in the way, that the researches never actually compared their results to actual available human CRON data.

I ignored it, because that's the polite thing to do when someone farts in a room.. sorry. Again, the questions you ask and the points you raise only show that you do not understand what you're talking about. And, typical of a farter, you deem yourself qualified to call a bunch of PhDs idiots, because they did not compare their results with something... that a priori cannot possibly match what they were looking for.

The human CR-data of the Fontana group is similarly compatible with the rodent data as the arbitrary mix of various starvation studies they use.

They could have used any starvation study, because all of them show exact same thing: namely, that after a period of adjustment (which indeed varies individually) a starving human will arrive at a metabolic point so vastly different from the homeostasis based on any diet (even a ketogenic one) that all other physiological characteristics become secondary.

could you enlight us with your superior understanding (meaning some arguments instead of general allegations)?

You need to read everything by George Cahill and Oliver Owen from 1960s on. And then read those who cite them (ex. Richard Veech). After you do that, come back and we'll talk. Then you will know enough to ask valid questions, which neither of you did so far.

And pelase do not as previously refer to the russian women who claims to live of zero kcal for month while doing exhaustive sport daily.

I never referred to any such thing. That woman (who, by the way is a medical doctor, a surgeon in fact) claims to live off 600kkal, not 0 as you absolutely wrongly state above. At least 2 of her desert treks done on this ration were well documented in Russian literature and are not disputed.

If you continue misinterpret what you read and hear, I see not point e-talking to you

[Guest]

I ignored it, because that's the polite thing to do when someone farts in a room.. sorry. Again, the questions you ask and the points you raise only show that you do not understand what you're talking about. [...] If you continue misinterpret what you read and hear, I see not point e-talking to you

WTF?? I apologize if I antagonized you, as my posts were not intended to insult you. What do you expect to gain when you use expressions as "f***er"?? This is hard at the border of trolling...

To the more professional points you raised:

I did not called the researchers "idiots" (I generally do not do that, regardless whether they are PhD's or not); but you used their research to imply that to mimic CRON in mice we have to do fasting. However, the point is, that they did not considered CRON in humans. The metabolic measures of human CRON are similar close to CRON mice as the starvation studies they compared it to (as provided in the paper). So, yes, starvation mimics mice CR - but the same way human CR mimics mice CR. And btw. there are also some inconsistencies in the numbers of the selected starvations studies they present, so there is a quite a range of what they consider "close" to CRed mice. Notably they do not provide an actual metric to quantify their conclusions.

And of course long term starving humans are different, but not in a positive or even life extending way. Short term fasting (what the researchers considered) on the other hand appears to be not that different compared to long term CRON diets.

Also what do you consider a "valid question" (really none of those raised so far)? And why is it important to have read "everything" from the mentioned authors and all papers that cite them from the last 40-50 years (judging from Scopus and Google Scholar entries this would be quite a task)? You have my respect that you have done so, but you hardly have to do so to argue at the kind of superficial level we are doing here. It's not exactly graduate class biochemistry vocabulary we are employing.

I misremembered the russian women, my bad. Its actually 300-600 kcal at her desert treks (+ limited amounts of water). Still quite an accomplishment, considering her performance resembling that of model athlets eating 3000 kcal ...


Again apologize if I misinterpret what I read and hear... try to improve that; promise.

Edited by Michael, 24 November 2010 - 08:18 PM.
Trim quotes

[kismet]

If you continue misinterpret what you read and hear, I see not point e-talking to you

Please, yes, take it elsewhere. Either you do as the thread starter did, make an honest and bright effort, or those who tried to poke holes in hir hypothesis, as scientist do, or you just take it to PM. Insults, assertions, ad hominems, bad science and name dropping does not constitute evidence. If you have made coherent contributions in the past thread I am sure you can do it again.

Add another one: Mild CR provides life extension benefits. Would not such a regimen produce similar eating patterns to ad lib? Does it not show that considerably shorter intervals are compatible with some sort of life extension?

Does life extension correlate better with calories or the fasting period? Why does life extension correlate with calorie intake up to actual starvation levels but intermittent fasting in rodents produces no benefit? Do you have evidence that IF produces overt harm like starvation that would counter-act the beneficial effects it should have as per your hypothesis? Why does IF fail?

Edited by kismet, 23 November 2010 - 09:44 PM.

[Michael]

The point I'm trying to make, the one people here have difficulty understanding --again, only because you did not take time to understand the metabolism of starvation-- is the difference between CR, when you eat sparingly, and starvation (bad word, I know, but..) when for a stretch of time you don't eat at all.

No, the problem is that you continue to ignore the clear evidence that CR per se, whether or not you "starve" and whatever the length between meals, is what retards aging and extends healthy life. You're engaged in metabolic hypothesis-spinning, while ignoring the empirical evidence on the subject.

Edited by Michael, 24 November 2010 - 08:10 PM.

[Brett Black]

No, the problem is that you continue to ignore the clear evidence that CR per se, whether or not you "starve" and whatever the length between meals, is what retards aging and extends healthy life.

My first post to this thread provided evidence that rodent caloric restriction experiments have involved long periods(metabolically speaking) of fasting compared to the ad-libitum fed control animals, and that these periods of fasting result in significant physiological changes in the CR'ed animals. On what grounds do you discount the possibility that these periods of fasting(and subsequent food-gorging) may be responsible for the retardation of aging(a questionable claim in itself, but off-topic) and extension of healthy lifespan observed in rodent CR experiments?

Edited by Brett Black, 25 November 2010 - 12:21 AM.

[Michael]

No, the problem is that you continue to ignore the clear evidence that CR per se, whether or not you "starve" and whatever the length between meals, is what retards aging and extends healthy life.

My first post to this thread provided evidence that rodent caloric restriction experiments have involved long periods(metabolically speaking) of fasting compared to the ad-libitum fed control animals, and that these periods of fasting result in significant physiological changes in the CR'ed animals. On what grounds do you discount the possibility that these periods of fasting(and subsequent food-gorging) may be responsible for the retardation of aging(a questionable claim in itself, but off-topic) and extension of healthy lifespan observed in rodent CR experiments?

Beginning with the data already presented from Nelson and Masoro (and yes, I do see that you made a plausible argument why these studies might not close the case for humans), reinforced by the grounds already clearly articulated by Matt, TFC, and Kismet.

Also, while you spend a significant amount of space outlining actual and likely metabolic differences between the relatively long-term fasting, CR mice and AL ones, the argument becomes highly hypothetical in connecting these to the anti-aging mechanisms of CR. Bergamini's lipolysis studies, in particular, have yet to show any actual lifespan benefit relative no healthy, well-nourished, genetically-normal animals; and on autophagy ... well, wait for forthcoming data from Cuervo's lab.

Edited by Michael, 25 November 2010 - 01:24 AM.

[xEva]

Mild CR provides life extension benefits.

Absolutely undisputed. And it will provide equally mild life extension.

Does life extension correlate better with calories or the fasting period?

I believe we need variability and so we need both.

Why ...intermittent fasting in rodents produces no benefit?

I think IF is too grueling for rodents. For them metabolically, it's like a human eating for a week and then starving for a week, and then again.. and again... it's fine to do for a while, but it can't be good as a lifestyle. It must eventually mess up their circadian rhythms. If it were up to me, I'd starve them only once a week or even a fortnight.. That would be far better -- but that's just my pet theory, of course.


The other thing is, I do not share your predilection for a perfect routine. I rather believe that metabolism should be trained in flexibility. Following a routine, however perfect, will only cause you to adapt to its narrow constrains, and then the first major change that will kick you out of it will also be your undoing. Humans are so successful, because we adapt to such a wide variety of diets, climes and lifestyles. A perfect diet is one that always changes -- with seasons at least. And surely, fasting is just the thing to do in between the dietary changes.

You're engaged in metabolic hypothesis-spinning,

No, I am not. It is a far-fetch hypothesis for you, because you have not studied the subject.