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Dean Pomerleau

Will Serious CR Beat a Healthy, Obesity-Avoiding Diet & Lifestyle?

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All,

In a number of different threads lately we've touched on the issue of whether human CR as traditionally conceived (i.e. consuming fewer calories while meeting one's nutritional requirements) will provide significantly greater health & longevity benefits than a healthy diet without dramatic calorie reduction, but which includes enough exercise and calorie-restraint to avoid becoming overweight/obese.

Several people, most notably & vocally, Michael and Saul, but also Khurram and Brian (who've sadly remain quiet lately) appear to hold the view that it's the absolute calories that count. Several others, including myself, Gordo, maybe James and maybe TomB, seem to think instead that human CR won't provide much (if any) additional health/longevity benefit beyond a healthy, obesity-avoiding diet & lifestyle.

This thread is meant to be a venue where we can duke it out on this topic.

In this post I'll try to kick things off by collecting together some of the evidence I've posted in the last few months, along with some new findings, which seems to me to undermine the hypothesis that CR will provide substantial benefits beyond those provided by a healthy, obesity-avoiding diet & lifestyle.

The disappointing (by my interpretation) NIH-sponsored Monkey CR trials are an important part of this evidence, but as Saul points out, that was just one study. In addition I'll point to evidence from rodents, dogs and people to make the case against CR providing significant additional benefits.

But before I dive in, I should note that what I'll be referring to is the practice of CR during one's years in the "sweet spot", not starting CR too young (before adulthood which might be beneficial in humans, but which is ill-advised and irrelevant for all of us), or continuing it too long into one's elder years. While the upper age cutoff may be controversial, I think there may be general consensus on this point - namely it's probably wise to back off serious CR at some point in one's 60's, 70's or 80's (depending on one's state of health) to avoid excessive frailty that may shorten rather than lengthen one's life. This topic of the optimal late-life BMI is discussed in detail in this thread, so let's not focus on it in this one.

I will also not address my strengthening conviction that if CR is to provide benefits in any mammal species, it likely needs to be accompanied by a significant degree of cold exposure. In other words CR without exposure to a cold environment (not just the subjective feeling of chilliness that virtually all CR folks experience) appears not to work to extend lifespan in rodents, to say nothing of people. For anyone who wants to learn more about the evidence for this cold exposure hypothesis, which I consider pretty compelling, see the cold exposure thread, and this post in particular to start with.

Evidence from Primates

First, the NIH CR primate study. Michael did what I consider to be the most comprehensive and authoritative review of this very important, multi-decade study of CR in rhesus monkeys. I won't try to recapitulate all the analysis Michael did, but do my best to summarize. I'm hopeful Michael will correct any mistakes or oversights in my interpretation.

I think Michael hit the nail on the head when he characterized the primate study (which was really two studies, at the U. of Wisconsin and at the NIA) as a "muddle". There were unfortunate shortcomings in both the study design and execution. The monkeys were of diverse and suspect pedigree which may have resulted in some of them dying earlier than they should have. The degree of CR in both the control monkeys and the CR monkeys was modest and in the later case may have dropped over the years to the point where it wasn't a very good test of CR (see [1]). And while I said I wasn't going to focus on it, the monkeys were housed at a thermoneutral temperature, potentially defeating CR benefits, per my theory about the importance of cold exposure on top of CR, as I discussed here.

With those caveats in mind, it seems to me the best interpretation of the two monkey CR studies are the following:

From the Wisconsin study [2], it appears that CR in monkeys can be effective - at least compared to controls who are allowed to become obese, and when both controls and CR monkeys are fed a highly refined, crappy diet similar in many respects to what an average American eats.

But the real kick in the teeth for human CR came with the publication in 2012 of the NIA monkey study results [3], which I summarized here as follows:
 

"The most parsimonious interpretation of the NIA monkey data (esp when coupled with the Wisconsin monkey data) is that once obesity is avoided, a healthy diet with (albeit only mild) calorie restriction is no better for primate longevity than the same diet without calorie restriction (or only enough CR to avoid obesity)."


Here are the survival curves for male (M) and female (F) control (CON) and 30% calorie-restricted (CR) monkeys, both for all-cause (left) and age-related (right) morality:

NIAprimateCR_PooledSurvivalDeCabo2293226


I don't know about you folks, but the corresponding CR and Control curves look pretty-darn indistinguishable to me. Hence the pessimism over the primate study results.

Having read both studies, it appears to me the primary difference between the Wisconsin and NIA studies were that the NIA diet was much healthier and less refined, and the NIA control monkeys were very modestly calorie restricted to prevent obesity and its ill effects, which appeared to plague the Wisconsin controls to a much larger degree. Hence the interpretation that CR doesn't seem to provide much if any longevity benefit in primates relative to controls eating a healthy, obesity-avoiding diet.

While acknowledging it's less than definitive, Michael seems to favor this interpretation of the Monkey CR studies as well, in this (extended) passage from is very thorough analysis of the monkey data, he acknowledges this as a pretty reasonable interpretation of the Wisconsin & NIA primate CR results, saying (my emphasis):


A straightforward reading of the two nonhuman primate CR studies, then, is that in rhesus macaques, the relationship between energy intake, body weight, and lifespan is the commonsensical one, against which the rodent CR phenomenon stands as such a stark contrast: that overweight and excess adiposity are bad for one's health and prospects for long life, but that some normative "healthy" anthropometry is optimal, with diminishing returns at best as energy intake and body weight are progressively reduced beyond that juste milieu. Indeed, skeptics of the human translatability of CR have long argued that the weight loss that is associated with CR appears to only be salutary to health within a relatively narrow range. They argue instead that further limiting energy intake and adiposity will lead to progressively less marginal benefit, especially in light of the uniquely metabolically deranging effects of visceral adipose tissue, which is preferentially lost early in the process weight loss, whether achieved by diet or exercise.(ref) Such skeptics also point to the importance of maintaining lean mass — both muscle and bone — for preserving health during aging, and to the large number of epidemiological findings (eg. (ref,ref)) suggesting a J-shaped or U-shaped relationship between body mass index (BMI) and mortality, although the relevance of these findings to the Calorie restriction phenomenon is dubious.*

In this interpretation, the slight restriction imposed on NIA control animals, leading to an energy intake and body weight that was intermediate between those of WNPRC's ad libitum and restricted groups, was sufficient to achieve or closely approach the point of diminishing health and longevity gains, and a further restriction from this point in the CR group therefore yielded no further extension of lifespan.

This explanation of the discrepancy in the effects of CR as compared to internal control animals in the WNPRC (2) and NIA (3) studies has much to offer. It is conceptually straightforward; it is consistent the major findings of the two studies, and with an important body of research in humans; it fits with some models of the postulated evolutionary basis for the slow-aging phenotype of CR; and is not exclusive of some of the other explanations we have explored. And, as we shall see in the next section, it can also provide a consistent explanation for several differences in health and metabolic outcomes between the two studies, and accommodate a broader body of research on diet and metabolism in nonhuman primates.


So Michael seems to concur that a good (perhaps the best) explanation of the disappointing CR primate results is that after calories are restricted enough to avoid obesity, there aren't many additional benefits to be had - "against which the rodent CR phenomenon stands as such a stark contrast."


Evidence from CR in Rodents

But is Michael even correct in his contrasting the failure of CR in primates with the success of CR in rodents?

In particular, is the "CR phenomena" in rodents really as robust and linear with degree of calorie restriction as nearly everyone (including Michael) have always contented? We're all familiar by now which this famous graph from Weindruch's study [5], apparently showing consistent increase in longevity with degree of CR in mice, right up to 65% CR, which must be pretty close to the point of starvation:
 

dbb1279dff6ba56fb1e18e8b22484bc8.gif


Looks very promising right?

But it turns out there are quite a few rodent CR studies that show only marginal benefits of CR beyond obesity avoidance. For example, in this post, I discuss ]study [6] from last year, which found that in F344 rats "10% CR increased life span to almost the same extent as 40% CR." There was some extra benefit of severe CR in the last few rats to die (maximum lifespan), but that was offset by early mortality in the severe CR group.

Overall the mean and median lifespans of the 10% CR and 40% CR rats were indistinguishable. And note these rats were CRed all their lives, from 6 weeks of age - which if anything should have maximized the benefits of severe CR and minimized the early mortality effect (which wasn't seen until middle age in the 40% CR group). Early onset CR is something none of us have the luxury of. The authors of [6] conclude:
 

These data in combination with the data from Duffy et al.,[ref] which reported that feeding rats 10% and 25% DR was as effective as 40% DR in reducing the early mortality of male Sprague–Dawley rats, demonstrate that the lifespan of certain strains of rats and mice does not increase linearly up to 40% DR. Most of the extension of lifespan appears to be achieved by levels of DR much lower than 40% DR.


And [6] isn't the only rodent study to show that mild CR is nearly as good as severe CR. In this post, I discuss [7], which studied lifelong CR in another commonly employed rat strain (Sprague Dawley rats). They found:

 

The average lifespan of AL rats was 115 <sic> months [they mean weeks].

At 104 weeks on study (110 weeks of age), the survival rate for the AL and

10%, 25%, and 40% DR groups was 63.4, 87.5, 87.5, and 97.5%, respectively.

The largest increase in survival (24.1%) occurred between AL and 10% DR,

indicating that very low levels of DR have a significant effect on survival.


This further supports the idea articulated above, that most of the benefits of CR, at least for the average individual, can be had via modest, 10% CR to basically avoid obesity. Unfortunately all the rats in this study were sacrificed early to study their organs, rather than allowing them to live out their natural lives, so there isn't data on total lifespan, just survival to 104 weeks.


One potentially troubling explanation for this discrepancy between successful mouse CR studies like Weindruch et al [5] and these less-successful rat studies is the highly in-bred nature of laboratory mice used in virtually all CR experiments. For example, Austed et al [8] studied early-onset 40% CR in male grand-offspring of wild-caught mice and found:
 

Although hormonal changes, specifically an increase in corticosterone and decrease in testosterone, mimicked those seen in laboratory-adapted rodents, we found no difference in mean longevity between ad libitum (AL) and CR dietary groups...


In fact they observed higher mortality in CR wild-type mice throughout most of their life, with a few wild-type CR mice hanging on longer than any of the AL-fed mice at the end of life. Here is the AL vs. CR survival graphs for these wild-type mice:
 

y0ptLiR.png


Importantly, the wild-type mice in [8] were literally fed as much food as they wanted, without any restriction. As a result, they were pretty overweight, topping out at around 32g in mid-life, which was nearly than twice the wild-type CR mice. But at 32g, this is still quite a bit less than the peak weight of really obese (and short lived) in-breed ad-lib fed mice, which often top out in the neighborhood of 40g in CR experiments.

So we see that in a less genetically inbred, obesity-prone strain of mice, severe CR may in fact be detrimental for longevity except for a few very lucky individuals - a small advantage that may have disappeared altogether had the control mice been mildly restricted rather than given unlimited access to food.

So in heavily inbred mice, the control mice get really obese and so CR which prevents obscene amounts of weight gain has benefits. But in naturally thinner wild-type mice, CR provided no average lifespan benefits relative to ad-lib fed controls.

Sohal et al have taken these clues about the importance of obesity avoidance in rodent longevity to heart, and done a really interesting study [9] that shows in both inbred mice and rats, that CR benefits are directly proportional to degree of obesity it prevents. In other words, as can be seen from these graphs, strains of rodents that get really fat when fed ad lib benefit a lot from CR, while strains that naturally don't get so fat benefit much less:
 

nihms602409f4.jpg


In short, Sohal et al argue that that what matters for lifespan benefits of CR is the amount of obesity burden avoided. In other words, in Sohal's model, obesity is like smoking. It not so much that CR (or not smoking) is actively good for your longevity. Instead, getting (and staying) obese is actively bad for you, just like picking up the habit of smoking is actively bad for you. And the more years you are obese, the worse it is for your longevity, just like the more "pack-years" you smoke, the worse it is for your longevity. The last sentence in Sohal's paper pretty much sums it up:
 

In a nutshell, CR increases life span when it counteracts a significant energy imbalance.


As a corollary, what Sohal is suggesting is that even in rodents, if there is no energy imbalance there will be little if any lifespan increase from CR. Put differently, avoiding obesity and maintaining an "energy balance" will get you most if not all of the benefits of CR.

Speaking of varying benefits of CR across mouse strains, I know Michael is pretty critical of this Nelson study [10], which looked at 41 different inbred strains of mice subjected to CR, and found a tremendous range of benefits and harm depending on strain and sex, as illustrated by this figure. Bars below the 0 line represent CR shortening lifespan relative to ad lib controls in a particular strain:

kBVu5j9.png


Regardless of Michael's criticism of the particular strains used in [10], which he mentioned at the recent Conference and which I discuss here, we shouldn't simply ignore these results. Instead, as good Bayesians, we should incorporate this negative result into our model representing the probability that CR will work in humans...

And it's not that we lack any good explanations for the potential life-shortening effects of serious CR. On the contrary, we've got an entire thread devoted to how CR weakens the immune response and makes animals much more likely to die from an illness once they get sick - a point brought home by the presentation by Dr. Janko Nikolich-Žugich at the Conference and discussed in this thread. This is one of the major reasons why I think there is general agreement that people should back off serious CR when they reach elderly years, to allow their (hopefully) preserved immune system to "recharge" and get ready for the slings and arrows of illnesses and injury that inevitably (at least for now) accompany old age.

Finally, like the successful Wisconsin primate study, (virtually?) all CR rodent studies feed both the CR and the control group pretty crappy, refined, unnatural diets of Purina rodent chow. It's no wonder eating less of a bad diet might give CR rodents a modest longevity advantage, just like was seen in the Wisconsin arm of the CR primate studies.

Does anyone know of rodent studies where they fed the CR and AL animals a more healthy, natural diet? Lacking evidence from a healthy-diet rodent CR study, it seems to me that the discrepancy between the Wisconsin and NIA primate CR results (which appears likely to have hinged at least in part on diet quality) calls into question the relevance of any of the positive results of CR in rodents.

In fact, it seems to me the only really credible rodent evidence would be a study of nearly wild-type mice (i.e. not heavily inbred), like the mice Austad used in [8], feeding them a healthy, natural diet either in modestly CRed amounts (i.e. 10% CR) vs. serious CR (40%). If the serious CR mice in such a study lived substantially longer, I'd interpret that as significant evidence in favor of CR efficacy. Short of that, I'd say none of the rodent data tells us very much.

Given what we do know, the available evidence (e.g. lack of mean/median lifespan benefits with wild-type mice fed a crappy diet completely ad lib [8]), suggests to me that the seriously CRed mice wouldn't have any advantage in the ideal experiment I describe.




Evidence from CR in Dogs


Before discussing evidence from humans, there is one more mammal species where CR has been experimentally investigated - namely dogs.

Here is the post where I discuss [4], a study of 25% CR in Labrador retrievers. Since I discussed it in detail in that post, I won't go into weeds about it here, but my summary of that study is:
 

The control dogs in this study were fed too much, given their caged lifestyle, so they grew fat. The CR dogs were fed an amount commensurate with (or a bit higher) than is recommended by canine nutrition experts, remained slim (in the lower part of the recommended weight range for Labradors) and lived 17% longer than controls, enjoying nearly as much CR longevity benefit as can be hoped for in [relatively long-lived] mammals.


In other words, it looks like in dogs, as well as monkeys and rodents, that simply avoiding obesity is where most if not all of the benefits of CR are to be had.

Evidence from Humans

So what about the species that really counts - humans? What can we learn from studies of people about the relative advantage of serious CR vs. simply avoiding obesity while eating a healthy diet?

Fresh in my mind is a discussion I had with Michael about [11], the recent, widely-discussed study (critiqued by me here - which includes my "fragile test tube" analogy) that appears to show that over the last 30-40 years, the healthiest BMI has shifted dramatically higher among healthy never-smokers, from an optimal BMI around 18 in folks in a cohort started in 1976-78 to a BMI around 26 in folks in a cohort started in 2003-2013.

I was surprised at what Michael said was the most likely explanation - which I hope he'll forgive and correct me if I get it not quite right.

What I understood Michael to be saying was that the reason the lowest mortality BMI has increased so much in the last 30-40 years is that, as the authors of [11] suggest, medical advances (e.g. statins, metformin, stents, etc.) have dramatically reduced the deleterious effects of being obese and overweight.

In short, being very thin doesn't pay as much as it used to in terms of longevity dividends. Very thin folks are still saddled with the burden of increased fragility (e.g. likelihood of dying if/when they get sick), while more robust chubby folks aren't penalized as much as they used to be for being overweight/obese as a result of the hundreds of billions of dollars that have been spent over the last few decades to develop treatments to prevent and manage the deleterious effects of obesity and obesity-related diseases like CVD and diabetes.

The reason I was a bit surprised by Michael's explanation for the cause of the increase in the healthiest BMI is that it would seem to undermine to some degree the motivation for practicing CR. By analogy, once vaccines, antibiotics and other medicines for combating infectious diseases were invented, one no longer needed to avoid infections like the plague (both literally and figuratively ☺). Similarly, since we can now prevent and/or manage the negative consequences of obesity better, it isn't as critical to stay rail-thin in order to live a long time.

But you should be thinking "but Dean, study [11] was in the general population - people who are lucky to live 75-80 years, with the last few years spent managing and suffering from diseases of excess. I don't want to live like that. I want to live a healthy life for as long as possible, free from any of the debilitating consequences of obesity. Surely serious CR is the best bet we have for accomplishing that - right? Isn't that what the Okinawans have shown us?"

In short, no. As I discussed in my post comparing Okinawans to Adventists, the Adventists, particularly male Adventists, live substantially longer than Okinawans eating their traditional diet, and the longest-lived Adventists had a "medium" BMI (22.5-25). In fact, according to [12], having a medium BMI added approximately 1.5-2.5 years to an Adventists' lifespan relative to a lower or higher BMI.

So in the the longest-lived population in the world, the clean-living, healthy-eating Adventists from Loma Linda California where (like us) they enjoy the benefits of modern healthcare, and where the men live to a ripe old average age of 87, the best weight to be is not rail thin, and therefore not seriously calorie restricted.

In short, based on the available evidence from primates, rodents, dogs and people, it appears to me that serious CR is unlikely to significantly benefit human longevity relative to a healthy diet eaten in moderation and coupled with an active lifestyle sufficient to avoid obesity and keep a person in the BMI "sweet spot" of ~20-24, or perhaps even 22-25.

--Dean

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[1] Neurobiol Aging. 2005 Jul;26(7):1117-27. Epub 2004 Dec 10.

Age-related decline in caloric intake and motivation for food in rhesus monkeys.

Mattison JA(1), Black A, Huck J, Moscrip T, Handy A, Tilmont E, Roth GS, Lane MA,
Ingram DK.

Author information:
(1)Laboratory of Cardiovascular Science, Gerontology Research Center, National
Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive,
Baltimore, MD 21224, USA.

Full text: http://gen.lib.rus.e...3&downloadname=

Human studies have documented age-related declines in caloric intake that are
pronounced at advanced ages. We examined caloric intake from a longitudinal study
of aging in 60 male and 60 female rhesus monkeys (Macaca mulatta) collected for
up to 10 years. Monkeys were provided a standardized, nutritionally fortified
diet during two daily meals, and intake was measured quarterly. About half of the
monkeys were on a regimen of caloric restriction (CR) representing about a 30%
reduction in caloric intake compared to controls (CON) of comparable age and body
weight. CR was applied to determine if this nutritional intervention retards the
rate of aging in monkeys similar to observations in other mammalian studies.
Following reproductive maturity at 6 years of age, there was a consistent
age-related decline in caloric intake in these monkeys. Although males had higher
intake than females, and CON had higher intake compared to CR, the sex and diet
differences converged at older ages (>20 years); thus, older CR monkeys were no
longer consuming 30% less than the CON. When adjusted for body weight, an
age-related decline in caloric intake was still evident; however, females had
higher intake compared to males while CR monkeys still consumed less food, and
again differences converged at older ages. Motivation for food was assessed in 65
of the monkeys following at least 8 years in their respective diet groups. Using
an apparatus attached to the home cage, following an overnight fast, monkeys were
trained to reach out of their cage to retrieve a biscuit of their diet by pushing
open a clear plastic door on the apparatus. The door was then locked, and thus
the biscuit was irretrievable. The time spent trying to retrieve the biscuit was
recorded as a measure of motivation for food. We observed an age-related decline
in this measure, but found no consistent differences in retrieval time between CR
and CON groups of comparable age and time on diet. The results demonstrate an
age-related decline in food intake and motivation for food in rhesus monkeys
paralleling findings in humans; however, we found no evidence that monkeys on a
long-term CR regimen were more motivated for food compared to CON. Examining the
relationship of selected blood proteins to food intake following 7-11 years on
the study, we found a negative correlation between globulin and intake among
males and females after accounting for differences in age. In addition, a
positive correlation was observed between leptin and intake in males.

PMID: 15748792

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[2] Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4. PubMed PMID: 19590001; PubMed Central PMCID: PMC2812811.
-----------
[3] Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R.Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012 Sep 13;489(7415):318-21. doi: 10.1038/nature11432. [Epub ahead of print] PubMed PMID: 22932268.

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[4] J Am Vet Med Assoc. 2005 Jan 15;226(2):225-31.
Influence of lifetime food restriction on causes, time, and predictors of death
in dogs.

Lawler DF(1), Evans RH, Larson BT, Spitznagel EL, Ellersieck MR, Kealy RD.

Author information:
(1)Néstle Purina PetCare Research, 835 S 8th St, St Louis, MO 63164, USA.

Free full text: https://www.avma.org...a_226_2_225.pdf

OBJECTIVE: To describe effects of lifetime food restriction on causes of death
and the association between body-mass characteristics and time of death in dogs.
DESIGN: Paired-feeding study.
ANIMALS: 48 dogs from 7 litters.
PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than
its pair mate from 8 weeks of age until death. Numerous morphometric and
physiologic measures were obtained at various intervals throughout life.
Associations of feeding group to time and causes of death were evaluated, along
with important associated factors such as body composition components and
insulin-glucose responses.
RESULTS: Median life span was significantly longer for the group that was fed 25%
less food, whereas causes of death were generally similar between the 2 feeding
groups. High body-fat mass and declining lean mass significantly predicted death
1 year prior to death, and lean body composition was associated with metabolic
responses that appeared to be integrally involved in health and longevity.
CONCLUSIONS AND CLINICAL RELEVANCE: Results were similar to results of diet
restriction studies in rodents and primates, reflecting delayed death from
species- and strain-specific intrinsic causes. Clinicians should be aware that
unplanned body mass changes during mid- and later life of dogs may indicate the
need for thorough clinical evaluation.

PMID: 15706972

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[5] Weindruch R, et al. (1986). "The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake." Journal of Nutrition, April, 116(4), pages 641-54.



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[1] Aging (Milano). 2001 Aug;13(4):263-72.

The effects of different levels of dietary restriction on aging and survival in
the Sprague-Dawley rat: implications for chronic studies.

Duffy PH(1), Seng JE, Lewis SM, Mayhugh MA, Aidoo A, Hattan DG, Casciano DA,
Feuers RJ.

Author information:
(1)Division of Genetic and Reproductive Toxicology, National Center for
Toxicological Research, FDA, Jefferson, AR 72079, USA. pduffy@nctr.fda.gov

Comment in
Aging (Milano). 2001 Aug;13(4):261-2.
Aging Clin Exp Res. 2002 Apr;14(2):152-4.

A study was undertaken to determine the effects of incremental levels of dietary
restriction (DR) in rats. Survival, growth, reproductive, and dietary intake (DI)
variables were monitored in a chronic study in which male Sprague Dawley (SD)
rats (NCTR colony) were fed their ration ad libitum (AL), or DR. The main
objectives were to determine if low levels of DR could be used to increase the
survival rate of SD rats in the chronic bioassay, and to identify the survival
characteristics of a long-lived SD rat strain (NCTR colony). The average life
span of AL rats was 115 months. At 104 weeks on study (110 weeks of age), the
survival rate for the AL and 10%, 25%, and 40% DR groups was 63.4, 87.5, 87.5,
and 97.5%, respectively. The largest increase in survival (24.1%) occurred
between AL and 10% DR, indicating that very low levels of DR have a significant
effect on survival. Whole-body, liver, prostate, and epididymis weights and body
length were decreased by DR, whereas brain weight, testicular weight, and skull
length were not altered by DR. Rats from the NCTR colony were found to be ideal
for chronic studies because they are much longer-lived than other SD stocks.
Although the 104-week survival rate for these SD, non-obese AL rats exceeds the
FDA's "Redbook" survival guideline (> 50%) for chronic bioassays, the use of DR
is advocated because it reduces individual variability in body weight.

PMID: 11695495

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[9] Free Radic Biol Med. 2014 Aug;73:366-82. doi:
10.1016/j.freeradbiomed.2014.05.015. Epub 2014 Jun 2.

Caloric restriction and the aging process: a critique.

Sohal RS(1), Forster MJ(2).

Free full text: http://www.ncbi.nlm....les/PMC4111977/

The main objective of this review is to provide an appraisal of the current
status of the relationship between energy intake and the life span of animals.
The concept that a reduction in food intake, or caloric restriction (CR), retards
the aging process, delays the age-associated decline in physiological fitness,
and extends the life span of organisms of diverse phylogenetic groups is one of
the leading paradigms in gerontology. However, emerging evidence disputes some of
the primary tenets of this conception. One disparity is that the CR-related
increase in longevity is not universal and may not even be shared among different
strains of the same species. A further misgiving is that the control animals, fed
ad libitum (AL), become overweight and prone to early onset of diseases and
death, and thus may not be the ideal control animals for studies concerned with
comparisons of longevity. Reexamination of body weight and longevity data from a
study involving over 60,000 mice and rats, conducted by a National Institute on
Aging-sponsored project, suggests that CR-related increase in life span of
specific genotypes is directly related to the gain in body weight under the AL
feeding regimen. Additionally, CR in mammals and "dietary restriction" in
organisms such as Drosophila are dissimilar phenomena, albeit they are often
presented to be the very same. The latter involves a reduction in yeast rather
than caloric intake, which is inconsistent with the notion of a common, conserved
mechanism of CR action in different species. Although specific mechanisms by
which CR affects longevity are not well understood, existing evidence supports
the view that CR increases the life span of those particular genotypes that
develop energy imbalance owing to AL feeding. In such groups, CR lowers body
temperature, rate of metabolism, and oxidant production and retards the
age-related pro-oxidizing shift in the redox state.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PMCID: PMC4111977
PMID: 24941891
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[10] Aging Cell. 2010 Feb;9(1):92-5. doi: 10.1111/j.1474-9726.2009.00533.x. Epub 2009
Oct 30.

Genetic variation in the murine lifespan response to dietary restriction: from
life extension to life shortening.

Liao CY(1), Rikke BA, Johnson TE, Diaz V, Nelson JF.

Author information:
(1)Department of Physiology, University of Texas Health Science Center at San
Antonio, San Antonio, TX 78229, USA.

Comment in
Aging Cell. 2010 Jun;9(3):448-9; discussion 450-2.

Chronic dietary restriction (DR) is considered among the most robust
life-extending interventions, but several reports indicate that DR does not
always extend and may even shorten lifespan in some genotypes. An unbiased
genetic screen of the lifespan response to DR has been lacking. Here, we measured
the effect of one commonly used level of DR (40% reduction in food intake) on
mean lifespan of virgin males and females in 41 recombinant inbred strains of
mice. Mean strain-specific lifespan varied two to threefold under ad libitum (AL)
feeding and 6- to 10-fold under DR, in males and females respectively. Notably,
DR shortened lifespan in more strains than those in which it lengthened life.
Food intake and female fertility varied markedly among strains under AL feeding,
but neither predicted DR survival: therefore, strains in which DR shortened
lifespan did not have low food intake or poor reproductive potential. Finally,
strain-specific lifespans under DR and AL feeding were not correlated, indicating
that the genetic determinants of lifespan under these two conditions differ.
These results demonstrate that the lifespan response to a single level of DR
exhibits wide variation amenable to genetic analysis. They also show that DR can
shorten lifespan in inbred mice. Although strains with shortened lifespan under
40% DR may not respond negatively under less stringent DR, the results raise the
possibility that life extension by DR may not be universal.

PMCID: PMC3476836
PMID: 19878144

-------
[11] JAMA. 2016 May 10;315(18):1989-1996. doi: 10.1001/jama.2016.4666.
Change in Body Mass Index Associated With Lowest Mortality in Denmark, 1976-2013.

Afzal S(1), Tybjærg-Hansen A(1), Jensen GB(2), Nordestgaard BG(1).

Full text: http://sci-hub.cc/10.../jama.2016.4666

Importance: Research has shown a U-shaped pattern in the association of body mass
index (BMI) with mortality. Although average BMI has increased over time in most
countries, the prevalence of cardiovascular risk factors may also be decreasing
among obese individuals over time. Thus, the BMI associated with lowest all-cause
mortality may have changed.
Objective: To determine whether the BMI value that is associated with the lowest
all-cause mortality has increased in the general population over a period of 3
decades.
Design, Setting, and Participants: Three cohorts from the same general population
enrolled at different times: the Copenhagen City Heart Study in 1976-1978
(n = 13 704) and 1991-1994 (n = 9482) and the Copenhagen General Population Study
in 2003-2013 (n = 97 362). All participants were followed up from inclusion in
the studies to November 2014, emigration, or death, whichever came first.
Exposures: For observational studies, BMI was modeled using splines and in
categories defined by the World Health Organization. Body mass index was
calculated as weight in kilograms divided by height in meters squared.
Main Outcomes and Measures: Main outcome was all-cause mortality and secondary
outcomes were cause-specific mortality.
Results: The number of deaths during follow-up was 10 624 in the 1976-1978 cohort
(78% cumulative mortality; mortality rate [MR], 30/1000 person-years [95% CI,
20-46]), 5025 in the 1991-1994 cohort (53%; MR, 16/1000 person-years [95% CI,
9-30]), and 5580 in the 2003-2013 cohort (6%; MR, 4/1000 person-years [95% CI,
1-10]). Except for cancer mortality, the association of BMI with all-cause,
cardiovascular, and other mortality was curvilinear (U-shaped). The BMI value
that was associated with the lowest all-cause mortality was 23.7 (95% CI,
23.4-24.3) in the 1976-1978 cohort, 24.6 (95% CI, 24.0-26.3) in the 1991-1994
cohort, and 27.0 (95% CI, 26.5-27.6) in the 2003-2013 cohort. The corresponding
BMI estimates for cardiovascular mortality were 23.2 (95% CI, 22.6-23.7), 24.0
(95% CI, 23.4-25.0), and 26.4 (95% CI, 24.1-27.4), respectively, and for other
mortality, 24.1 (95% CI, 23.5-25.9), 26.8 (95% CI, 26.1-27.9), and 27.8 (95% CI,
27.1-29.6), respectively. The multivariable-adjusted hazard ratios for all-cause
mortality for BMI of 30 or more vs BMI of 18.5 to 24.9 were 1.31 (95% CI,
1.23-1.39; MR, 46/1000 person-years [95% CI, 32-66] vs 28/1000 person-years [95%
CI, 18-45]) in the 1976-1978 cohort, 1.13 (95% CI, 1.04-1.22; MR, 28/1000
person-years [95% CI, 17-47] vs 15/1000 person-years [95% CI, 7-31]) in the
1991-1994 cohort, and 0.99 (95% CI, 0.92-1.07; MR, 5/1000 person-years [95% CI,
2-12] vs 4/1000 person-years [95% CI, 1-11]) in the 2003-2013 cohort.
Conclusions and Relevance: Among 3 Danish cohorts, the BMI associated with the
lowest all-cause mortality increased by 3.3 from cohorts enrolled from 1976-1978
through 2003-2013. Further investigation is needed to understand the reason for
this change and its implications.

PMID: 27163987


---------
[12] Arch Intern Med. 2001 Jul 9;161(13):1645-52.
Ten years of life: Is it a matter of choice?

Fraser GE(1), Shavlik DJ.

BACKGROUND: Relative risk estimates suggest that effective implementation of
behaviors commonly advocated in preventive medicine should increase life
expectancy, although there is little direct evidence.
OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and
smoking influence life expectancy.
METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those
eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed
questionnaire provided dietary and other exposure information at study baseline.
Mortality for all subjects was ascertained by matching to state death tapes and
the National Death Index.
RESULTS: California Adventists have higher life expectancies at the age of 30
years than other white Californians by 7.28 years (95% confidence interval,
6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88
years) in women, giving them perhaps the highest life expectancy of any formally
described population. Commonly observed combinations of diet, exercise, body mass
index, past smoking habits, and hormone replacement therapy (in women) can
account for differences of up to 10 years of life expectancy among Adventists. A
comparison of life expectancy when these factors take high-risk compared with
low-risk values shows independent effects that vary between 1.06 and 2.74 years
for different variables. The effect of each variable is assessed with all others
at either medium- or high-risk levels.
CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight,
and hormone replacement therapy, in combination, appear to change life expectancy
by many years. The longevity experience of Adventists probably demonstrates the
beneficial effects of more optimal behaviors.

PMID: 11434797

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Sorry to pollute your fine writing with my contribution, but...

 

The reason I was a bit surprised by Michael's explanation for the cause of the increase in the healthiest BMI is that it would seem to undermine to some degree the motivation for practicing CR. By analogy, once vaccines, antibiotics and other medicines for combating infectious diseases were invented, one no longer needed to avoid infections like the plague (both literally and figuratively ☺). Similarly, since we can now prevent and/or manage the negative consequences of obesity better, it isn't as critical to stay rail-thin in order to live a long time.

 

Yes: undermining motivation to continue practicing CR is certainly a challenge. But for me, I don't think I ever bought into the idea that in free-living humans CR would do much to extend lifespan. But I did buy into the idea that CR might improve healthspan.

 

Live long enough to benefit from the upcoming medical advances. CR alone with ON probably isn't going to do it. If it could do it, wouldn't we already see much longer lifespans amongst those throughout history already eating a healthy yet limited diet? Monks? Do they live longer? Cloistered nuns? Granted they mayn't have the perfect ON part of the equation, but still, why no radically long lived hermits?

 

I've given up the idea that CRON will extend my life out to Jean Calment's beauty. But maybe to my detriment I've not yet given up on the idea that by practicing CRON I may remain healthier in order to benefit from whatever SENS type medical miracles start walking across the waters.

 

These treatments are presumably decades away -- due to funding complaints -- but they're no doubt coming to fruition, I believe, unless we clobber ourselves and the planet before then.

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Sthira,

I hear you and agree 100%. I too want to stay healthy, in part because I don't want to suffer the negative effects of illness which are no fun, but also because I think by staying healthy I may be able to take advantage of future medical advances to help me live an even longer, healthier life.

All I mean to do with this thread is call into question and open up a dialog about the prevailing belief (or the belief that used to prevail at least) that "more is better" when it comes to restricting calories, as long as one maintains adequate (or "optimal") nutrition and avoids outright starvation and other psychological and physical pitfalls of severe CR.

What I'm suggesting is that the scientific evidence supporting the idea that serious CR will significantly beat a healthy, obesity-avoiding diet in humans is quite weak - even the bedrock evidence from rodents on which most optimism about human CR is grounded turns out to be pretty equivocal and contradictory when looked at carefully and in toto. Evidence from dogs, primates and humans is even less convincing.

So it may not be necessary and in fact might be counterproductive to dramatically restrict calories in an attempt to maximize our chances of living long and healthy lives, and taking advantage of future medical miracles.

Let me speculate about your case as an example. You enjoy and believe you benefit from extended water-only fasts, but sometimes feel you must cut them short to avoid becoming dangerously thin. Adding more calories to your daily diet when non-fasting, and thereby gaining some weight might allow you to engage in your occasional therapeutic water fasts for longer periods or more frequently while avoiding the problem of getting so skinny as to be dangerous or at least ill-advised. 

 

So carrying a few more pounds on your frame might benefit your quality of life, and per the evidence presented above, is unlikely to negatively affect your long-term health / longevity, or decrease your (sadly slim...) chances of achieving "longevity escape velocity".

--Dean

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Just so I understand...

 

Dean, you are positing that all those CR studies - thousands of them - going back all the way to the 30's are all a kind of illusion or parlor trick. They're all fatally flawed in all sorts of ways, or don't actually prove the claims that CR in fact extends max LS (except in certain edge cases of genetically lucky subjects). That CR does not really work to extend max LS even in the "star CR" case of rodents. Well, luckily rats don't live for very long, and unlike the case with monkeys or even dogs, we can readily conduct a most rigorous study of properly graduated adult onset CR rats that takes into account all possible flaws/confounders that we and science are aware of as of today - including non-damaged genetic strains, best rat nutrition, variety of temperatures, stimulating environment, etc., etc., etc. - and perhaps the CR Society can even underwrite such a study, which hopefully should be affordable(?). That way, at least we can find out if the CR effect exists at all in at least rats. That still won't tell us squat about long lived species such as monkeys, let alone humans, but at least we'd be able to confirm/deny the existence of the CR effect in short-lived mammals. So at least that's a question that's answerable in principle, and we are not limited to merely speculating. 

 

But ignoring all that, let us assume that CR does not work in humans. To say "benefits beyond those provided by a healthy, obesity-avoiding diet & lifestyle" opens a pandora's box of just what constitutes "healthy obesity-avoiding diet & lifestyle" along just the calories axis (this qualifier is critical). After all, you can avoid obesity either through minimal level CR/DR or at the other end through energy expenditure. Let us dismiss pharmacological approaches (such as fen-phen etc.). We are talking about exercise. Is it really all equal healthspan/lifespan whether one exercises lightly and avoids obesity, whether one consumes substantial calories and substantially expends them a la Dean P., or whether one consumes truly prodigious amounts of calories and exercises them all away a la the Olympic swimmer Michael Phelps. All avoid obesity. They're along a spectrum of BMI, but within the range of "healthy" as agreed to by medical science consensus. Does that mean that you can pick and choose how many calories you consume as long as you expend enough to stay within the range of obesity avoidance and are likely to reach your genetic potential of max LS/HS? I am of course assuming other variables to be kept the same and all healthy behaviors (i.e. not smoking, not drinking excessively, not mountain climbing etc.). 

 

That's the dilemma. The CR Society was formed around the idea that calories were a critical variable in healthspan/lifespan of humans, and we favored the lower end of the calorie bell-curve of consumption in humans. You are in effect saying that calories consumed are not an important variable at all. That opens a pandora's box.

 

Just clarifying for myself - correct me if I'm wrong.

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All I mean to do with this thread is call into question and open up a dialog about the prevailing belief (or the belief that used to prevail at least) that "more is better" when it comes to restricting calories, as long as one maintains adequate (or "optimal") nutrition and avoids outright starvation and other psychological and physical pitfalls of severe CR.

The "more is better" idea is definitely one I'm struggling with in my day to day life. All of us must make the best daily decisions about how best to stay healthy within the blizzard of marketplace hype. How much food should I eat; not eat; eat what, eat how much, eat when, how often; how much should we move, how much motion is too much, counterproductive to wear-n-tear issues, not enough, goldilocks....

 

These are big ole basic questions, and we have guidance from every direction we turn -- but which path to choose?

 

Do what feels good? But feelings are fickle. Do what Dr. Greger says? He's just as biased as anyone else. Whole foods plant based diet in "limited haha" quantities but high in presumed quality seems like it's winning my argument; but then wise counsel suddenly changes again. For example, cancer cells evidently need glucose to thrive, so now there are many voices speaking up for ketogenic diets. High fat? But wait -- oils are bad we're now told, even EVOO, and no please don't EAT the animals -- so high fat vegan keto is where I am now (I'm ignoring the EVOO is bad idea for now... But I buy it from consciously chosen places -- am I being duped by the olive freakos?)

 

And then there's the stress of making a living, paying rent, battling noise, pollution, traffic, people upstairs copulating all night, god calm down, then walk out the door and homeless people and people on corners for drugs, I'm straying away from your point, but your point was perhaps articulated by Plato:

 

How do we live decent, good lives during our brief visit here on beautiful planet earth?

 

What I'm suggesting is that the scientific evidence supporting the idea that serious CR will significantly beat a healthy, obesity-avoiding diet in humans is quite weak - even the bedrock evidence from rodents on which most optimism about human CR is grounded turns out to be pretty equivocal and contradictory when looked at carefully and in toto. Evidence from dogs, primates and humans is even less convincing.

But I'm not so confident the evidence is as weak as you indicate. You more than I know that thousands of studies have indicated that CR is beneficial to myriad species. Why are we so special to think CR won't "work" on the human species, too -- you're saying that? -- you're questioning how much CR is best for each practicing person, and there's just no way to know through organized, mainstream science. Are any researchers now conducting new studies investigating the levels of CR possibly beneficial to free-living people?

 

Nope. Why not ($$$ & time) and yet if we don't do it, eg, research CR ON on our own (n=1) then no one soon perhaps will do it, either (eg, study human CR)? Maybe someone will ramp up new CR studies (maybe this time with willing and dedicated and honest HUMAN BEINGS... not sad captive macaques who are tortured in prison cells) but we already live so long so that'll take oh-forever...

 

I'm still dreaming about artificial intelligence eliminating the need to actually do the empirical benchwork, and just run computer simulations. Dream dream dream, ha ha ha. Maybe medical AI can figure out that insanely complex and ever-dynamic human metabolism -- wtf is Calico doing? Some people do actually know...

 

So it may not be necessary and in fact might be counterproductive to dramatically restrict calories in an attempt to maximize our chances of living long and healthy lives, and taking advantage of future medical miracles.

Maybe...maybe not. It depends upon the person actually, honestly pursuing daily CR in the face of "muddledom."

 

Let me speculate about your case as an example. You enjoy and believe you benefit from extended water-only fasts, but sometimes feel you must cut them short to avoid becoming dangerously thin. Adding more calories to your daily diet when non-fasting, and thereby gaining some weight might allow you to engage in your occasional therapeutic water fasts for longer periods or more frequently while avoiding the problem of getting so skinny as to be dangerous or at least ill-advised.

 

So carrying a few more pounds on your frame might benefit your quality of life, and per the evidence presented above, is unlikely to negatively affect your long-term health / longevity, or decrease your (sadly slim...) chances of achieving "longevity escape velocity"

 

Right on, I'm with you, thanks for your suggestions. I'm now so thin and extreme -- I've been fasting so much recently, even combining prolonged fasting with IF: one meal per day spaced 24-hrs from the last -- that at the conclusion of each monthly fast I'm thinking: wait much longer for beginning another fast anew.

 

And yet I "believe" currently (and my belief is certainly flexible -- this ain't no dogma or religion for me -- fasting don't work? Screw fasting... And I'm onto the next best-formed sciencey idea for LEV. But I'm captive, you're captive, we're all waiting for Godot here.

 

But after fasting quite a bit now over the course of several years, I'm pretty darned healthy. Everyone thinks they're healthy of course and it's time for new blood tests for me (which feel like a waste of time and money, are incomplete snap shots anyway and only vague indicators of "good health...")

 

I'll heed your advice to put on more weight. Down at this level I definitely feel like I resemble a meth addict. Acquaintances (polite) say no, you're ok. Community of likeminded CR people living in close proximity would help.

 

And the thing about prolonged fasting is that the weight loss is "water weight" although I drink loads of water... But eating plants tends to bring me back up to non-meth looking dude standards in a week or two. My pattern is 3-7 or even 10 days of fasting per month -- is this too much, just right, not enough, and this is the point of your thread: who the hell knows? No one within my reach.

Edited by Sthira

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Tom,

 

Dean, you are positing that all those CR studies - thousands of them - going back all the way to the 30's are all a kind of illusion or parlor trick.

 

The idea I'm putting forth is that (virtually?) all the successful CR studies in mammals have been done using inbred genetically f**ked up rodents in germ-free environments eating crappy diets, the eating less of which would naturally improve health by avoiding obesity and the negative health consequences of the crappy chow.

 

I agree with you that a better study of rodents could be done, using adult onset CR in (nearly) wild-type mice fed a healthy diet, and given the opportunity for exercise in an enriched environment, perhaps at different temperatures as well. I'm surprised that such a study (perhaps without the temperature variation) hasn't been done. Maybe it has and I just don't know about... It seems pretty certain to me that the CRS is not in a position to sponsor such a study. We may have some money left, but not the kind of money it would take to sponsor such a study. 

 

Related to that, Khurram (if you're reading this) as I recall you used to keep rats yourself, as pets, and feed them a CR diet. Any interesting anecdotes you can share?

 

The CR Society was formed around the idea that calories were a critical variable in healthspan/lifespan of humans, and we favored the lower end of the calorie bell-curve of consumption in humans. You are in effect saying that calories consumed are not an important variable at all. That opens a pandora's box.

 

Very well said. You are right that it opens up a Pandora's box, although it is a box that has always been at least partially open. In particular, no one believes or has advocated that the healthiest approach is to absolutely minimize calories by laying in bed all day - although I seem to recall Kenton experimented with something like that years ago to minimize energy expenditure, going so far as to mount computer monitors on the ceiling above his bed, or something like that. But even he was surfing and engaging in other deliberate exercise during other parts of the day to maintain bone and cardiovascular health, IIRC. Kenton correct me if I'm wrong on these points. Even Michael got up in the middle of talks (even his own!) at the recent CR Conference and briefly wandered around the meeting hall to (presumably) avoid sitting for too long. I even heard a rumor that during the drive to the Biosphere he got out of the car at stoplights and jogged up to the car in front and back before the light turned green. A man after my own heart! 

 

Less anecdotally, there are plenty of instances where it's been shown fewer calories aren't always better for health & longevity.

 

There was the famous rats with cold feet experiment (discussed several places, including here) where rats who lived their lives standing in a cold puddle of water ate 44% more than normally-housed rats (spending more calories to stay warm), but nonetheless stayed thin and didn't live any shorter lives than the warm-housed rats. In fact they lived slightly longer and got less cancer. Even more direct evidence for the irrelevance of absolute calories at least in certain circumstances (cold exposure) comes from Koizumi et al [1] (discussed here and especially here) where typical C57BL6 mice were subjected to CR in either thermoneutral (30 °C) or "normal" (cold for mice) lab temperature (22 °C), and pair fed a CR diet to keep their weights identical (i.e. titrate the food amounts to keep both CR groups equally slim). The cold CR mice had to eat 20% more food than the warm CR mice in order to maintain their body temperature and not lose more weight than the warm CR mice. But it was only the cool CR mice that lived longer. In fact, the warm CR mice didn't live statistically longer (on average) than cool-housed control mice fed ad lib - despite eating half as much food, and weighing half as much as the cool-housed control mice. In contrast, the cool-housed CR mice also weighed half as much as controls, but had a median lifespan 40% longer than both the cool-housed controls and the warm-housed CR mice.

 

In short - when it comes to calories spent in thermogenesis, they don't appear to "count against you" when it comes to lifespan. In fact, to the contrary. Cold exposure and burning extra calories to keep warm might be critically important for living longer!

 

But your question was mostly about exercise. Fortunately, we have some rodent data on that too. In this post for example, I discuss [2] a study of the health effects of raising mice in a cool environment and giving some of them free access to a running wheel. How much did they voluntarily run? A heck of a lot - to the tune of 9 hours per day, a figure pretty familiar to me . The running mice ate a lot more than control mice (both were fed ad lib - unfortunately no CR groups for comparison) and so there wasn't a weight difference between the running mice and the sedentary mice. But nevertheless the running mice were much less susceptible to cancer, the leading killer of rodents, having a tumor burden that was 60% less than that of the control mice by the end of the study. So again we see a decoupling between absolute calorie intake and health / longevity, this time when the extra calories are expended in exercise.

 

But obviously where the sweet spot is in the complex space of calories eaten vs. optimal weight vs. calories spent exercising vs. calories spend keeping warm is a mystery for rodents, to say nothing of people. We are each an N-of-1 experiment in this regard...

 

--Dean

 

------------

[1]  Mech Ageing Dev. 1996 Nov 29;92(1):67-82.

A tumor preventive effect of dietary restriction is antagonized by a high housing
temperature through deprivation of torpor.
 
Koizumi A(1), Wada Y, Tuskada M, Kayo T, Naruse M, Horiuchi K, Mogi T, Yoshioka
M, Sasaki M, Miyamaura Y, Abe T, Ohtomo K, Walford RL.
 
 
Energy restriction (ER) has proven to be the only effective means of retarding
aging in mice. The mechanisms of multiplicity of effects of ER on aging remain,
however, fragmentary. ER induces daily torpor, the induction of which is reduced
by increasing the ambient temperature to 30 degrees C. The effects of preventing
hypothermia in ER animals were studied in terms of the expected consequences of
ER on survival, disease pattern and a number of physiological parameters in
autoimmune prone MRL/lpr mice and lymphoma prone C57BL, 6 mice. The results
demonstrate that torpor plays a crucial role in the prevention of lymphoma
development but does not have an affect on other aspects of ER, such as
prevention of autoimmune diseases.
 
PMID: 9032756
 

----------

[1] Cell Metab. 2016 Mar 8;23(3):554-62. doi: 10.1016/j.cmet.2016.01.011. Epub 2016

Feb 16.

Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent
NK Cell Mobilization and Redistribution.

Pedersen L(1), Idorn M(2), Olofsson GH(2), Lauenborg B(1), Nookaew I(3), Hansen
RH(4), Johannesen HH(4), Becker JC(5), Pedersen KS(1), Dethlefsen C(1), Nielsen
J(6), Gehl J(7), Pedersen BK(1), Thor Straten P(8), Hojman P(9).

Full text: https://sci-hub.io/1...met.2016.01.011

Regular exercise reduces the risk of cancer and disease recurrence. Yet the
mechanisms behind this protection remain to be elucidated. In this study,
tumor-bearing mice randomized to voluntary wheel running showed over 60%
reduction in tumor incidence and growth across five different tumor models.
Microarray analysis revealed training-induced upregulation of pathways associated
with immune function. NK cell infiltration was significantly increased in tumors
from running mice, whereas depletion of NK cells enhanced tumor growth and
blunted the beneficial effects of exercise. Mechanistic analyses showed that NK
cells were mobilized by epinephrine, and blockade of β-adrenergic signaling
blunted training-dependent tumor inhibition. Moreover, epinephrine induced a
selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies
blunted training-induced tumor suppression, intratumoral NK cell infiltration,
and NK cell activation. Together, these results link exercise, epinephrine, and
IL-6 to NK cell mobilization and redistribution, and ultimately to control of
tumor growth.

Copyright © 2016 Elsevier Inc. All rights reserved.

PMID: 26895752

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Sithra,

 

Very poetic and on-point as usual. As you say, we just don't know and we're all Waiting for Godot (great play ☺).

 

But one thing jumped out at me. You said:

 

My pattern is 3-7-10 days fasting per month -- is this too much, just right, not enough, 

 

How is that "3-7-10 days fasting per month" statement to be interpreted? Does it mean you fast for 3-days, 7-days and 10-days per month?! If so, that's a total of 20 days per month spent fasting. If this is the correct interpretation, I want to cast a strong vote for "too much!" especially if you're doing the longer ones solo and w/o medical supervision. But what do I know...

 

--Dean

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Well, luckily rats don't live for very long...

 

... and perhaps the CR Society can even underwrite such a study....

 

...That still won't tell us squat about long lived species such as monkeys, let alone humans...

So why do it? Rats are definitely cool, but are we really so curious about every aspect of their lives?

 

Study humans. Study us -- not (perhaps) for our own welfare -- but for the next generations of people behind us.

 

How to study us? Recruit us, ask us to report the cronometer dailies, then when we die add the data. This could be a focus of CRS -- and I really don't think it'd cost too much money. But the evil inside joke is we're not doing this for ourselves, we're doing this for the increased collected knowledge base. If no one knows what Dean is eating and how much, then no one knows haha. But if even a volunteer unpaid retired enthusiast grandfather type -- bored by golf and martinis or w/e they drink -- if one of us obsessive types gets ahold of a citizen science project, that may be more valuable than another rodent study. Your thoughts?

 

... I am of course assuming...

 

...not mountain climbing etc.).

Aww man mountain climbing isn't too dangerous -- not if you're smart and gear up and learn to tie knots and put this foot between that and now hold that ledge like this and up you go, mindfully moment by moment. It's more like meditation. Now driving a shiny metal box up the freeway to the mountain, that's way more dangerous!

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Sithra,

 

Very poetic and on-point as usual. As you say, we just don't know and we're all Waiting for Godot (great play ☺).

 

But one thing jumped out at me. You said:

 

My pattern is 3-7-10 days fasting per month -- is this too much, just right, not enough,

How is that "3-7-10 days fasting per month" statement to be interpreted? Does it mean you fast for 3-days, 7-days and 10-days per month?! If so, that's a total of 20 days per month spent fasting. If this is the correct interpretation, I want to cast a strong vote for "too much!" especially if you're doing the longer ones solo and w/o medical supervision. But what do I know...

 

--Dean

Haha yeah and if I was water only fasting twenty days per month your strong vote for too much would definitely be well cast! No, I'm fasting between 3-10 days per month. But. But! Um, sometimes during the boring ole middle of the month I might do a quickie 3-day fast just because I felt like it. But these little fasts in between are probably too much, and so I'm working on that moment by moment.

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Sthira,

 

Study us -- not (perhaps) for our own welfare -- but for the next generations of people behind us.... How to study us? Recruit us, ask us to report the cronometer dailies, then when we die add the data. This could be a focus of CRS -- and I really don't think it'd cost too much money...  if one of us obsessive types gets ahold of a citizen science project, that may be more valuable than another rodent study. Your thoughts?

 

I hear you. We had a brainstorming session at the CR Conference about how the CRS might get more involved in CR research, either in cooperation with university researchers or via "citizen science". Not too much came of it as far as I can recall, with the possible exception of trying to hook up with the folks at the National Weight Control Registry - a study which I am part of but which nobody else at the Conference was.  Michael took an action item to contact them on behalf of the CRS to see if we could get something formal going with them. Please don't try to join now - until Michael has talk to them on all of our behalf...

 

My doubt about the viability of our joint involvement in research (self-initiated or in collaboration with researchers) is that we aren't nearly as large or homogeneous a population as we used to be, say when Luigi Fontana started studying us. Many have drifted away from CR and the CRS, and those that remain have drifted apart in terms of diet and lifestyle, to the point where we're so diverse I'm not sure much could be learned from us as a group.  So I don't think simply pooling our diet, lifestyle, health markers and longevity data would tell us very much, to say nothing of producing publishable results. 

 

The only way I can imagine a citizen science project working would be if someone proposes a specific intervention that everyone agrees to follow and document, leveraging the combined power of our iron wills and proclivity for meticulous tracking.  

 

For example, we might all agree to measure our cholesterol via a standard panel of blood tests, then replace 200kcal of veggies with 1.5 TBS of high polyphenol EVOO per day for a month (of visa versa for folks already consuming a lot of EVOO), keeping the rest of our diets unchanged from our usual fare, and then repeat the blood tests to see if high quality EVOO is as toxic as some people claim. We might do something similar with a moderate (e.g. 3-day) fast. I can imagined the combined results of that kind of intervention-based citizen science study could provide useful insights, and perhaps even be publishable, at least in one of the open-access journals and particularly if led by someone with a PhD and nutrition research credentials.

 

I'm fasting between 3-10 days per month.

 

I'm relieved to hear that. You had me scared there for a while!

 

--Dean

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Great summary Dean.   I share your skepticism.  Culturally most CR practitioners are optimizer, and I suspect that the marginal utility of adding another phytochemical or health intervention including even CR declines in an already health population as suggested by Novick

 

The observational data in humans is plagued with potential biases but may offer some suggestion of upper limits since so many diets are out there across the globe and time.  Notably the 7th Day Adventists have the benefit of more robust healthcare than in Okinawa.  Comparisons of populations across space, culture, and time are plagued with many potential factors such as this that may be responsible for differences.  Observational datasets while having an important place in the hierarchy of evidence may be riddled despite excellent methodology with not only inaccurate data and missing potential variables/confounders, but also by inadequate granularity in measured variables to fully control for it, and over-controlling by collinear (too closely associated variables) above and beyond the problems with ecologic comparisons between one study group and another.

 

There is also the challenge of applying population data to individual circumstances.  We are dealing aggregate data in a competing cause of death scenario.  In one population CR may have a net minimal favorable impact on survival due to higher infection rates offsetting lower systemic inflammation and slowing of the biologic clock so to speak.  In another population or individual, the risk of infection with public health, the advent of effective antibiotics, etc. may be substantially reduced.  These probabilities are Baysian: the probability in an individual or population are contingent on other variables idiosyncratic to that individual or population.  Notably neither population strictly followed a CRON diet and while the overall populations studied are large, it is not clear to me whether the study had adequate statistical power to discern an effect size at the lowest end of BMI.  Even large numbers of very low BMI may represent inadequate surrogate variables for true CR. 

 

So here's the bottom line as I see it: With the quality of data I have seen so far in humans, I can't say with confidence whether CR extends life in humans or by how much.  I certainly suspect, if there is any, it would be significantly less than, say, some subspecies of the rodent population given the limited absolute range of human mortality dates in the record book so far.  However I also can't rule out some significant effect although the data on compression of morbidity is much more compelling as of today.

 

Usually when there is gray data, a larger range of practices emerges and this certainly applies here taking a poll even in this specialized forum.  All the more so when the dividing line between "healthy, active, non-obesogenic" etc. diet and CR in my mind is a gray one up for interpretation over a wide breadth of practices too. 

 

This suggests to me that above and beyond the non-obese, active, low BMI diet etc. where data is stronger, the pursuit of CR beyond this should ideally enhance rather than detract from quality of life broadly defined by the individual, or if not that, at the very least for the practitioner to be comfortable and at peace with the inherent risks and uncertainties that various degrees of CRON lifestyle represent.  This is very personal.  In my own life, for example, I practice IF (rather than CRON per se) because of the overall health and quality-of-life benefits relative to other lifestyle approaches.  This is a moving target as the literature changes as well as my own preferences, experiences, and goals over time.

 

 

Edited for clarity 6/20/16

Edited by Mechanism

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Dean, I enjoyed reading your original post. It is fascinating! Thank you!

 

You said,

 

“In short, based on the available evidence from primates, rodents, dogs and people, it appears to me that serious CR is unlikely to significantly benefit human longevity relative to a healthy diet eaten in moderation and coupled with an active lifestyle sufficient to avoid obesity and keep a person in the BMI "sweet spot" of ~20-24, or perhaps even 22.5-25.(BMI sweet spot).”

 

I am curious about how you would act upon that conclusion. Would you gain weight from your current BMI 18 to 20 or even 22.5?

Edited by gracezw

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Grace,

 

 I am curious about how you would act upon that conclusion. Would you gain weight from your current BMI 18 to 20 or even 22.5?

 

Good question. In fact I have intentionally gained few pounds over the last couple months. This morning I was 123lbs, or a BMI of 18.5. Whether I'll decide to gain any more weight will depend in part on how my biomarkers look, based on my bi-annual blood test I plan to get in the next couple weeks. 

 

BTW - are you still been unable to figure out how to use the quote button I explained here?

 

--Dean

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Good question. In fact I have intentionally gained few pounds over the last couple months. This morning I was 123lbs, or a BMI of 18.5. Whether I'll decide to gain any more weight will depend in part on how my biomarkers look, based on my bi-annual blood test I plan to get in the next couple weeks.

 

That is good to know! My guess is that even if you gain more weight, your biomarkers and blood test will still look good.

 

 

 

BTW - are you still been unable to figure out how to use the quote button I explained here?

 

Thank you for your nice and clear explanation. I got it. 

 

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If you look at some of the results raw foodists are getting, then you'd see that CR doesn't seem to give that much benefit when you look at objective markers of health. On the other hand, they do seem to be restricted somewhat, or at least they were until the rise in popularity of some in that community who promoting much higher calorie diets rather than moderation. 

My expectations for how much CR will extend lifespan have been lowered, but I still think it's much greater than the most conservative estimates of just two years extra life. Obviously we can't give a number, but we do have data from Seventh Day Adventists, Okinawan's, and also other studies looking at long term lifestyle habits and longevity. 

 

The two monkey studies had problems, like you mentioned. They never responded exactly how rodents or us humans respond to CR, especially the female monkeys in the NIA study. It's hard to also quantify how much some of these inconsistencies can mitigate CR's effect on lifespan. We know in lab animals that you can alter many things and lose some of the benefits of CR. That could be as simple as increasing the ambient temperature, or increasing the intake of AGE's in the diet. So, given that the monkeys didn't respond how we expected, I don't know how much we can translate that to us, since humans seem to respond better. Maybe there was something about the diet, or the level of restriction that prevented some of the differences from occurring, but a pilot study to try to induce these changes at whatever calorie intake might've been helpful. 

 

Just speculation, but I think we can still expect, as a conservative estimate, 10 year extension in lifespan if a person starts at 30 on moderate CR. I don't doubt that many of us who start young will quite easily reach our mid 90s, and many of us reach 100 and beyond. If you look at objective measures of health and various other biomarkers in the offspring of centenarians, then they display more of a CR-like phenotype than the average person. But having seen the results over the years of people on CRON, we still objectively have far better results than those people who 'genetically' are predisposed to increased healthspan and longevity.

I want to also make a comment on species specific mortality. Dogs on CR: many of them were euthanised at some point when they had little quality of life due to severe disease, one being hip dysplasia or arthritis which is something that is more specific to dogs as a cause of death. If CR had a very good effect on prevention of cancer, heart disease, diabetes etc in dogs then it wouldn't matter much if hip dypslasia were to get them in the end, even if biological ageing were slowed, because it's more of a mechanical issue. So who knows how long they'd live otherwise. Just an anecdote, but my dog reached almost 20 years and suffered hip dysplasia / severe arthritis, but was otherwise very healthy for his age... Sadly we had to put him down, but we feed him very well; vegetables, small amount of fruit and meat.

Given the fact that we only have one life, I can't see any other choice right now. I don't regret doing the level of CR I've done over the years. The benefits I feel from the diet make it worth it anyway.

Edited by Matt

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Matt,

 

Thanks for your perspective. I agree with almost everything you say except maybe:

 

Just speculation, but I think we can still expect, as a conservative estimate, 10 year extension in lifespan if a person starts at 30 on moderate CR. I don't doubt that many of us who start young will quite easily reach our mid 90s, and many of us reach 100 and beyond. 

 

I think you are likely right that we could reach mid-90s, maybe even 100 via CR if started in early adulthood and practiced consistently.

 

But even today Seventh Day Adventists, following a healthy lifestyle and eating a clean (mostly) veg(itari)an diet are living to between 87 (men) and 90 (women) on averagewithout significantly restricting calories and with an average BMI around 24.

 

So how does the math work out that starting CR in early adulthood will give us 10 extra years (conservatively) relative to a healthy diet & lifestyle sans CR, by allowing us to live into our mid 90s, when the Adventists are already living nearly that long now and will certainly be living into their mid-90s on average in ~40 years when we are that old?

 

--Dean

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Matt,

 

One other thing your thoughtful response brings to mind. You mention CR in certain breeds of dogs (like Labradors, where CR has been tested) might not work, or work as well, because they die of unusual, species-specific causes, like hip dysplasia. Specifically, you said:

 

Dogs on CR: many of them were euthanised at some point when they had little quality of life due to severe disease, one being hip dysplasia or arthritis which is something that is more specific to dogs as a cause of death. If CR had a very good effect on prevention of cancer, heart disease, diabetes etc in dogs then it wouldn't matter much if hip dypslasia were to get them in the end, even if biological ageing were slowed, because it's more of a mechanical issue.

 

I agree with you - that is one possibility. But I hope you recognize that your argument cuts both ways. If CR helps prevent dog- (or Labrador-)specific causes of morbidity/mortality, it might artificially inflate the apparent effectiveness of CR, relative to how well it would work in other species that aren't afflicted by the same dog/labrador-specific maladies. Happily for dogs and their owners, but sadly for humans in general, that appears to be exactly the case.

 

As you mention, dogs in general, and especially larger dogs, and especially Labradors, suffer from hip dysplasia and osteoarthritis to a degree that it sometimes requires them to be "put down" to prevent suffering. That is precisely what happened quite recently to Roscoe, my neighbor's gorgeous (both physically and in temperament) Burmese Mountain Dog (BMD) - one of the most handsome, but also largest of dog breeds. This is exactly what he (and virtually all of them) look like, except at 7 years old he was quite a bit chubbier:

 

shutterstock_188662199.jpg

 

This picture almost exactly matches what Roscoe looked like near the end - still very handsome, but also pretty chubby:

 

7oUD2rA.png

 

And there is the rub - pun intended. In particular, when dogs get overweight, it puts stress on their joints, and they aren't well-designed to handle it. Being overweight also leads to inflammation which exacerbates their osteoarthritis problems. The bones in their joints rub against each other, then they degenerate, causing dogs to limp and experience pain. It was hard to watch Roscoe try to walk. With lots of pain, they don't walk or run much, so they get fatter, in a viscous cycle. Eventually it gets so bad that we humans euthanize them, out of compassion, a kindness we paradoxically and irrationally don't extend to our fellow humans, since human life is "sacred"...

 

But back to the CR connection. By reducing a dog's weight, and reducing inflammation, CR is particularly well-suited to combating the biggest problem large dogs like Labradors and BMDs face - osteoarthritis (OE). In fact, the same folks from Ralston Purina who did the Labrador CR longevity study [1], also used the same cohort of Labradors in an earlier study of CR and osteoarthritis [2]. They found that indeed, CR dramatically reduced the prevalence, severity and progression of OE in this same group of dogs. They found:

 

Radiographic evidence of osteoarthritis that affected multiple joints
was significantly more common in the control-fed group than in the limit-fed
group. Prevalence of lesions in the hip joint was 15/22 in the control-fed group 
and 3/21 in the limit-fed group. Prevalence of lesions in the shoulder joint was 
19/22 in the control-fed group and 12/21 in the limit-fed group; lesions in this 
joint were generally mild. Severity, but not prevalence, of osteoarthritis in the
elbow joint was greater in the control-fed group than in the limit-fed group.
 

They conclude that:

 

Food intake is an environmental factor that may have a profound effect on development of osteoarthritis in dogs.
 

So if five years earlier than the Dog CR study was published, the same mild CR protocol (i.e. enough to prevent obesity) was preventing / slowing OE in this same group of dogs, and if OE was what eventually causes these dogs to die or be euthanized, it's not surprising that obesity-avoiding mild CR (modestly) extended their lifespan. But since humans almost never die (and are never euthanized!) as a result of OE, even this modest longevity benefit of obesity-avoiding CR observed in dogs wouldn't be evidence that CR will slow aging or extend lifespan in humans - right?

 

More generally, different species die of very different causes. Rodents, almost always die of cancer and (for example) rats overwhelmingly die from one type of cancer - leukemia. As we know, it appears (mostly from rodent studies...) that CR is particularly good at preventing cancer. But dying of cancer in general, and leukemia in particular, is much less common (although obviously not uncommon...) in humans. So this calls into question just how relevant the remarkable benefits of CR in rodents are for humans, a topic I discussed in detail in this post entitled What's Lost in (Rodent) Translation? Here is the most relevant section from that post, where I said:

 

As you can see from the table above, like most rodents, a clear majority died from various forms of cancer, with leukemia being by far the most common single cause. As we all know (and which is graphically illustrated here) cardiovascular disease in its various forms is the #1 killer of humans (at least in the US and other developed nations) - cancer only accounts for 23% of human death. Further, leukemia is only the 6th most common cancer killer in people, accounts for only 5% of all cancer deaths and only ~1% of all causes of death in the US.

 

Based on this cause-of-death mismatch, these leukemia-prone rats, and cancer-prone rodents in general, don't seem like a very good model of the "diseases of aging" that kill people. As a corollary, the fact that CR40 significantly reduced leukemia deaths relative to CR10 in [ref] seems unlikely to "move the bar" for human longevity, even if these results would translate directly to people.

 

So the takeaway message from this one seems to be that even CR rodent results, which have always been the best data we have to support large additional lifespan benefits of 'serious' CR relative to simply avoiding obesity, may be open to question both in terms of the magnitude of the benefit, and their translatability to humans.

 

And note - that rat study didn't employ an unusual, leukemia-prone strain of rats. They were standard F344 rats used in a large portion of CR rodent studies. In F344 rats, 50-75% of them die of various forms of cancer.

 

In short, mammal species where CR has been (more or less) consistently demonstrated to extend lifespan (i.e. rodents) die as a result of very different distribution of diseases than humans. So even if CR does work in rodents, and we assume the same benefits we see in rodents translate directly to humans, it's not clear how much extra lifespan CR will provide human beings because of the mismatch between causes of in our species vs. theirs. In fact, it's pretty commonly acknowledged that curing all cancers, without improving prevention/treatment of other causes of death, would only add a couple extra years to the average human lifespan.

 

Now obviously I believe CR also helps prevent or delay our #1 killer too, cardiovascular disease. What I'm not convinced about is whether weep-to-your-knees 25-40% CR will be any better at combating cancer, CVD or any of the other major causes of human mortality than a healthy, obesity-avoiding diet and lifestyle, since there is very little evidence to support this idea in other mammal species, and quite a bit of evidence suggesting serious CR isn't required to gain the extra ~10 years of life that optimistic human CR practitioners are hoping for, most notably evidence from the comparison of Adventists vs. Okinawans.

 

--Dean

 

--------------

[1] J Am Vet Med Assoc. 2005 Jan 15;226(2):225-31.
Influence of lifetime food restriction on causes, time, and predictors of death
in dogs.
 
Lawler DF(1), Evans RH, Larson BT, Spitznagel EL, Ellersieck MR, Kealy RD.
 
Author information:
(1)Néstle Purina PetCare Research, 835 S 8th St, St Louis, MO 63164, USA.
 
 
OBJECTIVE: To describe effects of lifetime food restriction on causes of death
and the association between body-mass characteristics and time of death in dogs.
DESIGN: Paired-feeding study.
ANIMALS: 48 dogs from 7 litters.
PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than
its pair mate from 8 weeks of age until death. Numerous morphometric and
physiologic measures were obtained at various intervals throughout life.
Associations of feeding group to time and causes of death were evaluated, along
with important associated factors such as body composition components and
insulin-glucose responses.
RESULTS: Median life span was significantly longer for the group that was fed 25%
less food, whereas causes of death were generally similar between the 2 feeding
groups. High body-fat mass and declining lean mass significantly predicted death
1 year prior to death, and lean body composition was associated with metabolic
responses that appeared to be integrally involved in health and longevity.
CONCLUSIONS AND CLINICAL RELEVANCE: Results were similar to results of diet
restriction studies in rodents and primates, reflecting delayed death from
species- and strain-specific intrinsic causes. Clinicians should be aware that
unplanned body mass changes during mid- and later life of dogs may indicate the
need for thorough clinical evaluation.
 
PMID: 15706972
 
----------

[2] J Am Vet Med Assoc. 2000 Dec 1;217(11):1678-80.

 
Evaluation of the effect of limited food consumption on radiographic evidence of 
osteoarthritis in dogs.
 
Kealy RD(1), Lawler DF, Ballam JM, Lust G, Biery DN, Smith GK, Mantz SL.
 
Author information: 
(1)Pet Nutrition Research Department, Ralston Purina Company, St Louis, MO 63164,
USA.
 
 
OBJECTIVE: To determine prevalence of radiographic evidence of osteoarthritis in 
4 diarthrodial joints of dogs with restricted feed intake, compared with dogs
without restricted feed intake.
DESIGN: Paired feeding study.
ANIMALS: 48 Labrador Retrievers.
PROCEDURE: Dogs in litters from 7 dams and 2 sires were paired by sex and weight 
within litters and randomly assigned to a control-fed group or a limit-fed group 
that received 25% less food than the control-fed group. Radiographic evaluation
of prevalence and severity of osteoarthritis in the hip, shoulder, elbow, and
stifle joints was performed when dogs were 8 years of age.
RESULTS: Radiographic evidence of osteoarthritis that affected multiple joints
was significantly more common in the control-fed group than in the limit-fed
group. Prevalence of lesions in the hip joint was 15/22 in the control-fed group 
and 3/21 in the limit-fed group. Prevalence of lesions in the shoulder joint was 
19/22 in the control-fed group and 12/21 in the limit-fed group; lesions in this 
joint were generally mild. Severity, but not prevalence, of osteoarthritis in the
elbow joint was greater in the control-fed group than in the limit-fed group.
CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence and severity of osteoarthritis in 
several joints was less in dogs with long-term reduced food intake, compared with
control dogs. Food intake is an environmental factor that may have a profound
effect on development of osteoarthritis in dogs.
 
PMID: 11110459

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This has sort of come up in this thread but hasn't been explicitly stated.  I actually think there is a third, fourth, and even fifth, etc. 'vs' here.

 

They question of a serious DR/CR diet vs. a healthy obesity avoiding lifestyle is interesting. It would be incredibly fascinating to know how the following would do:

 

Serious CR/DR vs. obesity avoiding vs. ad lib WFPB (at 0%, 5%, 10% animal products) vs. intermittent fasting vs. SAD vs. raw foodist vs. low GI CR - and to take it a step further, every permutation of those listed.  Of course the idea that such data could ever exist feels like a pipe dream.

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This has sort of come up in this thread but hasn't been explicitly stated. I actually think there is a third, fourth, and even fifth, etc. 'vs' here.

 

They question of a serious DR/CR diet vs. a healthy obesity avoiding lifestyle is interesting. It would be incredibly fascinating to know how the following would do:

 

Serious CR/DR vs. obesity avoiding vs. ad lib WFPB (at 0%, 5%, 10% animal products) vs. intermittent fasting vs. SAD vs. raw foodist vs. low GI CR - and to take it a step further, every permutation of those listed. Of course the idea that such data could ever exist feels like a pipe dream.

My opinion is what diet works best for you is the diet that's targeted to your own intimate issues. We have some good thumbnails -- eat a whole foods plant based diet rich with leafy greens, a wide variety of cruciferous veggies, legumes, nuts, seeds, non-sweet fruit like berries, eat loads of fiber. We "know" this on a large scale for many people:,"eat food, mostly plants, not too much." But this is just the starting point (a broken record repeated over and over in the literature -- replicating ad infinitum is fine for undergrads seeking another thesis but for us it's wasting time, money, energy, patience...) for you as an individual. From this presumably solid starting point (WFPB), find your own specific dietary shortcomings that are particular to you. Cronometer is helpful here (if we agree on RDA science, which appears to be the best info we've got?) because maybe you need more B12 and D and selenium. Maybe you're fine on those but need more choline and dietary calcium and biotin. Why bother with more general studies investigating which diet is better for the human masses -- CR or vegan or raw... We already have a solid foot here on this turf. Now the challenge becomes: do it. Eat WFPB diet every day for the rest of your 147 years remaining before the bicycle crash that finally sends your body to Alcor. Edited by Sthira

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I second Sthira's thumbnail sketch of a healthy and (hopefully) life-prolonging baseline diet. Yes Drew, there are lots of minor variations on this baseline. But in the grand scheme of things, my gut tells me none of the tweaks you listed will make a huge difference either way. As someone I respect a lot says, the human body is a flex-fuel vehicle. It can do pretty well on lots of different diets, as long as the core is there, which Sthira does a good job enumerating. I will say this though. Some will say I'm biased, but one thing seems pretty clear to me based on the Adventist data - the less animal products the better. 

 

Sthira wrote:

...eat loads of fiber.

 

Coincidently, I'm putting the finishing touches on a long (and hopefully controversial) post about this very topic (fiber). In fact, I'd be done by now if I hadn't spent most of yesterday chewing on my phone. ☺

 

Stay tuned.

 

--Dean

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Hi Matt!

 

I agree with everything that you said -- and I disagree strongly with Dean (who I respect and admire in most ways).  I think that Dean put too much stock in the NIAA study -- as noted by Dr. J. at CR IX, who indicated that he had been involved in that study, it  was flawed in many ways  --  e.g., monkeys of different races added in the middle, unbalanced in sexes, etc.  That study should be ignored -- flawed, and also much too small.

 

Prof. Spindler had a nice statement:  If CR doesn't extend lifespan in humans, then it makes humans a unique animal.

 

  --  Saul

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I will say this though. Some will say I'm biased, but one thing seems pretty clear to me based on the Adventist data - the less animal products the better.

And that's because we're healthy eating vegans. Emphasize the "healthy" in "vegan" because obviously we can also be unhealthy vegans. French fries and pop! I'm vegan first because I love animals and hate how they're abused just because people are willfully ignorant and lazy, and because multinationals are busy poisoning food supplies for profit and fun.

 

But eating as a healthy vegan doesn't work in everyone's particular situation. Some fish (low food chain, young fatty sardines, eg) some of the time (if you're confident they're relatively unpolluted -- ha!) for some people under some particular circumstance is probably healthy. Or not. Depends. Same probably goes for eating insects, eating lab chow, eating shit like quorn, lab-created artificial meat, eating organic eggs, grass-fed red meat -- whatever that is -- or dairy, or swilling wine, tippling alco, rolling herb, or tripping on medicinal mushrooms twice per year as needed, or wasting money on experimental unregulated possibly dangerous nootropics, or ballzin down with micro or macro doses of LSD, n1 self trials with experimental pharma (metformin for healthy young people?), experimental supplements (resveratrol? NR? pterostilbine? C60 olive oil, down down down we go the rabbit hole whee..)

 

I don't eat animals not because I believe eating animals is necessarily unhealthy; I don't eat animals because animals are cool and animals "deserve" to not be treated like shit, tortured, then eaten for fun. They live their own lives. We can eat just fine without sacrificing animals for greedy earth-gobbling human appetites -- so why sacrifice land and trees and jungles and pollute streams and air and foul up water for everyone when vitamin B12 is cheap and easily bought?

 

I also think (since you're still reading Sthira rant here) that more dietary studies are a waste of time, effort, and money. Perfect your diet from birth to death, and maybe, perhaps, as de Grey repeats over another pint of whatever he's stinging down, maybe you'll get a few extra years of healthy lifespan. Eat well to protect your good health; eat well not to have much hope that eating perfectly will help you live any longer. For that, we need new pipeline stuff out of labs.

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Prof. Spindler had a nice statement: If CR doesn't extend lifespan in humans, then it makes humans a unique animal.

That's a great quote. Got a reference and context for it?

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Sthira wrote:

And that's because we're healthy eating vegans.

 

I don't know about you, but I haven't eaten a vegan in at least a couple weeks ☺.

 

I'm vegan first because I love animals and hate how they're abused just because people are willfully ignorant and lazy, [more right righteous vegan ranting...]

 

Here here! I couldn't have said it better myself. 

 

Some fish (low food chain, young fatty sardines, eg) some of the time (if you're confident they're relatively unpolluted -- ha!) for some people under some particular circumstance is probably healthy.

 

Fish are friends, not food. And they can recognize our faces.

 

--Dean

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