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Dean Pomerleau

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

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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?

 

Nobody is saying that CR won't (modestly, at least) extend lifespan in humans. Certainly not me. All I'm saying is that the evidence is far from clear that it will extend it significantly better than a healthy, obesity-avoiding diet.

 

--Dean

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I think the single biggest difference between humans and other animals is that there are billions of humans and we have excellent information regarding how long each human lives and the causes of death.  And we have a lot of historical info as well.  So for humans more than any other animal there is a pretty well defined bell curve of life expectancy.    And as our numbers, knowledge and technology exploded geometrically the outliers at the top of that bell curve have increased rather modestly.  The assumption that an untargeted general reduction in calories is somehow going to magically elevate one to a point outside of that bell curve which comes from a fantastically large pool of genetic and environmental diversity strikes me as wishful thinking.

 

I'm highly sceptical of the expectation that there is going to be a technological breakthrough that is going to provide a jump to immortality or even a massively longer lifespan especially for large numbers of people.  If there is it would likely be a catastrophe.  It's hard to imagine anything more potentially disruptive to our social and environmental structures which are already straining under humanity's explosive growth in numbers and the explosive growth in our ability to exploit and appropriate natural resources.

 

I'll venture out on a limb and say caloric restriction has been proven effective in countering obesity and has a role to play in many health issues with a metabolic component from cardiovascular disease to cancer.  If you know what is killing you early or what your greatest future health risks are likely to be than getting control of one's diet provides a powerful tool for addressing them.

 

If one considers the huge numbers of people suffering from obesity and it's increased risks of diabetes, cardiovascular disease and cancer it's completely reasonable to believe that wide spread adoption of modest caloric restriction would result in a significant upward shift in average life expectancy and might contribute to modestly enlarged numbers at the very top of our life expectancy bell curve perhaps contributing to the possibility for new records of maximum lifespan by an individual.

Edited by Todd Allen

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Maybe the "Obesity-Avoiding" Part Isn't Even Critical...

 

Hot on the heels of the reasonably convincing study [2] (discussed here) that found the optimal BMI for minimizing mortality has shifted upwards dramatically over the last 40 years (from 18 to 26!), comes this new study [1] (popular press account), which makes a pretty convincing argument that healthy lifestyle habits are what count for longevity; one's weight (and by extension, calorie intake) make almost no difference. Blasphemy, I know. But read on.

 

Here is what the study did and found. They followed almost 12,000 adult men and women from the NHANES III cohort for an average of 14 years (during which time about 2300 died) to see how their weight and lifestyle habits correlated with mortality. In particular they assessed the mortality implications of four (self-reported) healthy lifestyle habits as a function of weight. They were:

  1. Consumption ≥ 5 servings of fruits or vegetable/day
  2. Regular exercise > 12 times per month
  3. Moderate alcohol consumption (up to 1 drink per day for women and up to 2 drinks per day for men)
  4. Not smoking

Those habits form a pretty low bar by the standards of people around here, but only a very small fraction of the general population actually meet this meager baseline for a healthy lifestyle. Among the 12K people in this study, here are the percentages for 0,1,2,3 and 4 healthy habits that people self-reported adhering to: 2%, 12.7%, 32.2%, 34.6% and 18.5%. In other words, fewer than 20% of the study population adhered to all four healthy habits. Interestingly, these healthy habit adherence percentages didn't vary much at all across weight categories - e.g. in all three weight categories between 16 and 20% of people reported adhering to all four habits.

 

As you can well imagine, the more of the four healthy habits participants engaged in, the lower their mortality. Compared with folks who followed all 4, people who didn't do any of the healthy habits were over 3x more likely to die during the follow-up period, after adjusting for a bunch of potential confounders. Here are the hazard ratios from Table 2 of the free full text:

 

YY6QQ3H.png

 

Here is which habits helped the most, depending on one's BMI. Interestingly, for normal weight folks (BMI 18.5 - 24.9), exercising more than 12 times per month didn't provide any advantage over exercising 1-12 times per month. Both resulted in about a 40% reduction in mortality risk relative to thin/normal weight people who never exercised.

 

4jkjKM5.png

 

Here is what overall interpretation the author's gave regarding adoption of additional healthy habits:

 

In the pooled analysis that included all individuals in the cohort (normal weight, overweight, and obese), the adoption of each additional healthy habit decreased all-cause mortality between 29% and 85% (Table 2). To put this in perspective, statins decrease all-cause mortality by 12% in individuals at high risk for cardiovascular disease [ref].

 

So quite clearly, the more healthy habit you engaged in, the better. But how did weight or BMI play into these benefits, and how did the benefits compare across weight categories? That's where things get really interesting, and relevant for this thread.

 

Here is the critical graph from the paper, showing mortality hazard ratio (relative to someone of normal weight with all four habits) on the Y-axis relative to the number of healthy habits, subdivided by BMI category, along the X-axis:

 

wy7ceue.png

 

As you can see, there is a dramatic payoff to being thin if you've got a really crappy lifestyle (i.e. zero healthy habits). But once you've adopted even just one healthy habit, you gain no advantage by being thin relative to being overweight (BMI 25-30). Even more surprising, once you've adopted two or more healthy lifestyle habits, it doesn't matter what your weight is. In particular, with two or more healthy lifestyle habits, you gain no mortality advantage from being thin/normal weight relative to being obese.

 

The authors acknowledged a few weaknesses of the study, none of which seem to me to seriously undermine its results. Here is the weaknesses section of the paper's discussion:

 

The study also has several noteworthy weaknesses. First, the cross-sectional nature of the interview portion of the survey did not account for changes in lifestyle habits over time. This may be considered a limitation even though lifestyle habits seem to be relatively stable in adulthood.[refs] Second, the survey was dependent on the accuracy of self report of healthy habits. Third, although healthy habits were associated with decreased mortality, association does not prove causation. Finally, control variables were limited to age, race, and sex in the survival analysis because of uncertainty about how lifestyle interacted with other commonly used control variables such as socioeconomics or marriage.

 

This study seems to drive home the point made in [2], in spades. It really doesn't seem like weight (and therefore calorie intake) has nearly the negative influence on mortality that it apparently used to be, back before the 1970's and 80's - when it really paid to be thin as discussed in the thread about [2].

 

It would have been nice if they'd subdivided the lowest BMI category into 18.5-22 vs. 22-25, but based on [2] (which found in the last couple decades that being really thin had no mortality advantage over being even moderately overweight) I seriously doubt they would have seen any different results, and there probably weren't enough very thin people in the study to break them out for separate analysis.

 

This seems to me like even more compelling evidence that "it's the lifestyle, stupid" and not the calories that count for longevity.

 

So perhaps it's time to simplify the title of this thread, to "Will Serious CR Beat a Healthy Obesity-Avoiding Diet & Lifestyle?" and conclude based on [1][2] and all the other evidence I've presented in previous posts in this thread, that the answer is most likely "no".

 

--Dean

 

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

[1] J Am Board Fam Med. 2012 Jan-Feb;25(1):9-15. doi: 10.3122/jabfm.2012.01.110164.

 
Healthy lifestyle habits and mortality in overweight and obese individuals.
 
Matheson EM(1), King DE, Everett CJ.
 
Author information: 
(1)Department of Family Medicine, Medical University of South Carolina,
Charleston, SC 29425, USA. Matheson@musc.edu
 
 
BACKGROUND: Though the benefits of healthy lifestyle choices are well-established
among the general population, less is known about how developing and adhering to 
healthy lifestyle habits benefits obese versus normal weight or overweight
individuals. The purpose of this study was to determine the association between
healthy lifestyle habits (eating 5 or more fruits and vegetables daily,
exercising regularly, consuming alcohol in moderation, and not smoking) and
mortality in a large, population-based sample stratified by body mass index
(BMI).
METHODS: We examined the association between healthy lifestyle habits and
mortality in a sample of 11,761 men and women from the National Health and
Nutrition Examination Survey III; subjects were ages 21 and older and fell at
various points along the BMI scale, from normal weight to obese. Subjects were
enrolled between October 1988 and October 1994 and were followed for an average
of 170 months.
RESULTS: After multivariable adjustment for age, sex, race, education, and
marital status, the hazard ratios (95% CIs) for all-cause mortality for
individuals who adhered to 0, 1, 2, or 3 healthy habits were 3.27 (2.36-4.54),
2.59 (2.06-3.25), 1.74 (1.51-2.02), and 1.29 (1.09-1.53), respectively, relative 
to individuals who adhered to all 4 healthy habits. When stratified into normal
weight, overweight, and obese groups, all groups benefited from the adoption of
healthy habits, with the greatest benefit seen within the obese group.
CONCLUSIONS: Healthy lifestyle habits are associated with a significant decrease 
in mortality regardless of baseline body mass index.
 
PMID: 22218619
 
----------
[2] -----------
[1] 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).
 
 
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

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Dean, thanks for analyzing this 2012 study of Healthy lifestyle habits and mortality in overweight and obese individuals! It is great to hear when I have been having such a hard time losing the same 5 pounds! First I need to suppress my food cravings when I am alone. I am also torn between staying away from home kitchen as planned and being pulled by my 11-year-old son for helping him prepare his food. His eating window is different from mine. And I don’t do well as I should in an already very selected list of social events which unfortunately still have some food sharing themes.

 

I guess I will rest for a couple of days. Then I will keep working on being 5 pounds lighter to reach my college weight. It will be a big personal challenge and a desirable test on my willpower/self-discipline.

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New Rodent Evidence Against Serious CR

 

Hold onto the handrails calorie restriction fans, the "serious CR" boat is about to get seriously rocked once again.

 

This brand new study [1] (also posted by Al to the email list a few days ago) is a massive paper with many moving parts by a bunch of famous CR researchers from many different universities and research institutes. It includes original experiments in yeast, worms and mice - that's how comprehensive this study is. In this post I'll focus on what I consider to be the most important findings which are relevant to this thread - namely their rodent experiments. Everyone is welcome to read the free full text (and accompanying supplemental material) for all the other details I don't cover, especially regarding the biochemistry of the CR response. As you'll see (and probably regret) it is quite a handful just covering all the interesting details from the mouse part of their study.

 

With that intro out of the way, here are the details of the mouse CR experiment they conducted. The researchers tested two common strains of lab mice, C57BL/6J and DBA/2J (herein referred to as B6 and D2, respectively, following the authors' convention) on three different diets - ad lib, 20% CR or 40% CR relative to the ad lib group.

 

The ad lib mice were actually ad lib - i.e. given free access to food 24/7, no minor CR to avoid obesity going on with that group... CR was introduced gradually over 4 weeks starting at 6 months of age (about the human equivalent of age 30 - so not immediately after weaning) and continued until they died. The mice were housed 3-4 per cage at a standard (cold-for-mice) lab temperature of 20-22 °C. 

 

So how'd they do? You'll be surprised, unless you already agree with me that serious CR is a bad idea... Read 'em and weep Michael:

 

pwdMdjJ.png

 

Note: All the black bars & lines throughout this post represent the AL mice, blue ones are for the 20% CR groups, and red are for the 40% CR groups (think danger ☺).

 

First let's look at the survival curves (A), which are broken down into four graphs, by strain and gender on the left of the figure. If you prefer to see the mean, median, 25% and 10% max longevity data, it is available in Table S1 in the supplemental material, which I've captured as in image but not embedded here for clarity & brevity.

 

As you can see, the 50% survival times for both male and female D2 mice (lower survival curves) are identical. On average, D2 mice lived just as long on 20% CR as 40% CR relative to true, pig-out ad lib. Admittedly, the last few surviving D2 CR40 male mice appear to have had a very modest longevity advantage (which wasn't statistically significant BTW, see full table linked above), but look at the even bigger early mortality disadvantage the male CR40 D2 mice had relative to both AL and CR20, pointed to by the red hand icon in the lower right survival graph. Obviously the D2 mice results were far from a ringing endorsement of serious (40%) CR relative to modest (20%) CR. Quite the contrary, there was no mean or max lifespan advantage of CR40 over CR20 in either gender.

 

But it gets even worse for the weep-to-your-knees CR fanboys. Look that the longevity curves at the top from the C57BL/6J mice - which BTW is the canonical strain of mice for CR experiments, not some genetic f*cked up mice that Michael always likes to criticize when the results don't go his way...

 

Here where we see 40% CR really sucked. In fact, in the female B6 mice, not only was their an early mortality effect of 40% CR relative to both 20% CR and ad lib (see top red pointy hand), the females were at a (albeit modest) survival disadvantage relative to ad lib throughout most of their lives, with only the last few percent of CR40 mice able to hang on to barely match the longevity of the ad lib female B6 mice. How pitiful is that!? Meanwhile the female CR20 B6 mice kicked butt in the longevity department (top left green checkmark) living 40% longer than either ad lib or 40% CR counterparts. Hurray for modest CR!

 

A similar, but not as dramatic pattern was seen in the male B6 mice. Here, CR40 was able to beat ad lib, but the CR20 mice beat both ad lib and CR40 groups (right green checkmark), although the CR20 advantage over CR40 wasn't statistically significant in males like it was in female B6 mice.

 

Next let's look at the lifetime weight trajectories of the mice (right four graphs above). As you can see, by 20 weeks of age (human age ~30) all the mice had gotten a little pudgy, having been fed AL up to that point. All the ad lib mice continued to gain weight, getting really obese until late in life when they got sick and lost weight precipitously. The 20% CR groups all did what I'm suggesting is the right way to go for people - namely their weight came down a bit from their young adulthood peak and stayed in a healthy range, not too fat and not too thin. In contrast and not surprisingly, the CR40 mice lost quite a bit of weight over time, and stayed rail-thin throughout the study.

 

In short, across both sexes and two common strains mice, very modest, adult-onset, obesity-avoiding 20% CR (relative to a completely ad lib obesity-producing diet) did at least as well, and often a lot better, than serious 40% CR, in two strains of mice where the CR response is supposed to be most robust and reproducible!

 

So much (once again) for the Weindruch CR study [2] of female C57BL/6J and the sexy survival graph gracing the CRS home page, which I've reproduced below with the the addition of ages in weeks along the bottom to make comparison easier. Next to it is the survival graph of the corresponding group of female B6 mice from [1], reproduced and blown up from above:

 

 

SiIer7d.png2HZMtKB.png

 

There are several things that are really interesting about these two graphs.

 

First, let's compare the survival curves for the ad lib controls (green on the left, black on the right). Both the 50% survival and 10% max longevity were virtually identical in the control groups across the two studies (~120 weeks and ~150 weeks, respectively).

 

Now let's look at modest CR groups in both studies, conveniently represented by the blue lines in both graphs. In the Weindruch study in the left graph, this corresponds to 25% CR, vs 20% CR for the blue line on the right from [1], which are close enough to each other for comparison's sake.

 

The average survival in the two studies for modest 25/20% CR was virtually identical - around 155 weeks. The max lifespan (longest 10%) was actually slightly longer in the current study [1] than in Weindruch (~180 weeks vs. ~160 weeks). This, despite the fact that the mice in [1] weren't started on CR until the human equivalent of 30 years old, vs. immediately after weaning in the Weindruch study (this is weird, since spending more of one's life at a given level of CR is supposed to result in additional longevity benefits, according to conventional wisdom).

 

The fact that the ad lib groups and modest CR groups had virtually identical survival curves, with (if anything) a lifespan advantage in favor of later onset, less severe CR (CR20 vs. CR25) in mice from this new study [1], suggests that the surprising results of [1] (CR20 longevity ≥ CR40 longevity) were not caused by poor animal husbandry, which is the other excuse Michael often likes to trot out to dismiss results he doesn't like...

 

Finally, it's almost too obvious and painful to point out, but the 40% CR mice crashed and burned in the current study [1] (red curve in right graph), while much more severe CR (55% and 65% CR!) worked great for Weindruch (pink and red curves in left graph) - Weindruch saw no early mortality effect from severe CR and a dramatic additional mean and max lifespan extension for truly weep-to-your-knees CR relative to both ad lib and modest CR.

 

So what gives? Why such a stark contrast between the smashing success of severe CR in Weindruch vs. the abject failure of serious CR in similar females from the same strain in [1]?

 

One explanation that won't work is Tom's (and Michael's) so-called "Hunger Hypothesis", and not just for all the reasons I give on the thread about that lame idea. In this case, given the low weight (and low leptin - shown later) of the CR40 mice in [1], it would seem pretty tough (to put it mildly) to argue that the CR40 mice weren't hungry enough, and downright laughable to suggest they were less hungry than the longer-lived CR20 mice. So that's not gonna cut it.

 

Here is one partial explanation the authors' suggest for the failure of CR40 to beat CR20 (my emphasis in this and all future quotes):

 

Here, fasting levels of insulin, glucose, and IGF-1 were reduced with CR across all experimental groups, thus representing a global and consistent effect of CR on improving insulin sensitivity (Mitchell et al., 2015b). In most cases 20% CR was sufficient to produce a dramatic decrease in these parameters with little to no further benefit by 40% CR. 

 

Sure enough, the table below from the supplemental material bears out what the authors say. I've color-coded it the same ways as the graphics above, with black (actually grey) values represent the AL mice, blue ones are for the 20% CR groups, and pink are for the 40% CR. As you can see, in virtually all strains, sexes and important blood biomarkers (including IGF-1, IGFBF-1, Insulin, Glucose, Insulin Sensitivity, Adiponectin, and Leptin), both CR groups have dramatically different values than the ad lib mice, and they are different in what we generally believe to be the "good" direction. In most of the biomarkers, 40% CR resulted in little additional change in the "good" direction relative to 20% CR. But in two important and controversial, closely-related (and inversely correlated) biomarkers (IGF-1 and IGFBF-1), CR40 had a consistently larger impact than CR20 - i.e. CR40 mice had much lower IGF-1, and much high IGFBF-1 compared with both AL and CR20 mice, as you can see from the first two columns of the table below:

KXSPg1y.png

In short, this table, when coupled with the survival data, may explain why CR40 didn't beat CR20 in [1]. In particular, it suggests that the changes in biomarkers the CR20 animals exhibited were sufficient to trigger the "CR Response", and the further changes brought about by CR40 were either negligible, or in the case of IGF-1 and IGFBF-1, where dramatic additional changes with CR40 did occur, they were unnecessary and apparently counterproductive when it came to boosting longevity.

 

In short, CR20 was enough, and CR40 was overdoing it when it came to changes in biomarkers and longevity.

 

But the explanation that CR20 was enough to change important biomarkers sufficiently to boost longevity does not account for the glaring discrepancy between the benefits of very severe CR55 and CR65 in the Weindruch study and the failure in [1] of less-severe CR40 to beat CR20, or even an AL diet in some cases.

 

For that discrepancy, It seems to me the most plausible explanation is the difference in age of CR onset. Specifically, Weindruch started his mice on CR abruptly, immediately after weaning. Study [1] started CR gradually in young adulthood, once the mice were fully growns. Sadly for serious CR believers, this is exactly the state each of us were in when we started CR...

 

Unlike Michael's recent, self-described ex cathedra pronouncement to the contrary, the CR Response really does look pretty fragile and hard to get right. It can be messed up by lots of things, as the authors of [1] clearly point out in the discussion section:

 

CR has long been the measuring stick and gold standard for alternative strategies to improve health and survival in biomedicine by manipulating cellular and molecular mechanisms of aging. However, emerging evidence calls into question the universality of the effects of CR in extending mean and maximal lifespan. These life extension effects may be influenced by common experimental variables such as species, genetic background, sex, macronutrient composition and meal timing, degree of restriction, age of onset, and their interactions. ... Our results provide further evidence that multiple factors alter the response to CR and that while the effect of CR on health appeared consistent across strains and sexes, survival was not correlated with CR in all cases.

 

And they go on to point out with lots of references that "thin isn't always in" when it comes to CR benefits:

 

The universal effects of CR on lifespan were challenged recently in a number of studies in wild-derived mice (Harper et al., 2006), inbred strains (Fernandes et al., 1976, Forster et al., 2003, Goodrick et al., 1990, Harrison and Archer, 1987 and Turturro et al., 2002), and recombinant inbred strains (Liao et al., 2010 and Rikke et al., 2010). Indeed, body weight loss and reduction in core body temperature were not proportional to the number of calories consumed or to survival... Mice that responded the best on survival outcomes were those that preserved their fat mass better into the second year of life, suggesting that there is a minimum level of adiposity that is necessary for the full benefit of CR and that the contribution of this organ to metabolic regulation under CR condition is crucial. These results are congruent with the work of Liao et al. (2011) showing that strains of mice with the lowest reduction in fat under CR were more likely to have extended lifespan. Furthermore, long-lived strains, such as the Ames and Snell dwarf mice, have higher percentages of body fat [and higher BW-normalized metabolic rate - DP] even though they are smaller than their littermates. Indeed, recent work has shown in humans that slight overweight is associated with the lowest level of all-cause mortality (Flegal et al., 2013 and Grabowski and Ellis, 2001).

 

Apparently serious CR, and the rail-thin physique resulting from it, can seriously mess you up if too severe and started in adulthood, at least if you're a mouse. And frankly, if serious, adult-onset CR doesn't work any better than an obesity-avoiding diet in rodents (to say nothing of monkeys), why do people still think it will work in humans better than a healthy, obesity-avoiding diet?

 

It saddens me to argue this - I've spent more than a decade of my life (up until recently) hungry and thin in the pursuit of "traditional", low-calorie CR, hoping it will buy me longevity benefits, as have many people here. But in the sage and seemingly prophetic words of our CRS President Brian Delaney from late last year:

 

The CR Society is committed to being more pro-science than pro-CR. That is, if the science starts pointing to doubts about CR, than the Society needs to acknowledge those doubts.

 

I say 'prophetic' on account of Brian's long recent silence in this community - starting not too long after that post in fact. Checking his account, the user BrianMDelaney hasn't posted to these forums since early March, and was a no-show at the recent CR Conference, without telling anyone he wasn't going to be there, which among other things, wasn't cool. And it's not like he's dropped off the face of the earth. Brian continues to post daily to his personal Facebook account, and more paradoxically, even logs into these forums regularly - in fact as recently as yesterday. His continued public silence around here is just plain weird if you ask me... (sorry to creep on you Brian if you're reading this).

 

As we've speculated about elsewhere, I suspect Michael's nearly complete disengaged with this community and especially Brian's long silence are at least in part a result of their seeing the writing on the wall - namely that serious CR is unlikely to be beneficial in humans, and as a result have lost faith & interest in the topic, and in Brian's case, perhaps the practice as well.

 

Speculating, perhaps they are just too embarrassed by their change of heart to tell the rest of us, and instead choose to simply drift away. As a result the dream of serious CR extending human lifespan is going out with a whimper, rather than a bang, through slow attrition. Hopefully the last true believer (Saul? Al?) will turn off the lights when they leave...

 

As Max Planck said:

 

“A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.” 

 

Or as he put it more succinctly: 

 

“Science advances one funeral at a time.” 

 

Hopefully in our case the 'funerals' Planck speaks of are only metaphorical - former active members actually see the light (or more accurately, see the dim prospects for human CR), and slowly drift away, rather than literally dying.

 

And hopefully literal funerals won't be necessary before the remaining true CR believers come to see the light and shift their perspective; rationally recognizing the increasingly strong scientific evidence that CR will not only be futile, but potentially harmful for humans when started in adulthood and practiced with too much rigor, i.e. much beyond the point of obesity avoidance.

 

But speaking of scientific evidence, and getting back to [1], I don't want to be too much of a Debbie Downer, so I'll try to leave everyone with a ray of hope. Check out the following. First off, recall from my overview above, the mice in [1] were all housed in cold conditions for mice (20-22 °C). I bet some of you can guess where I'm going from that clue...

 

Below I've reproduced the survival curves again, and next to them show the rectal temperatures of all the different groups of mice. The most glaring thing to notice is that the longest lived group of mice, the female B6 mice on 20% CR (blue line in upper left graph), had the highest rectal temperature of any group in the study (leftmost blue bar in the righthand graph). In fact, all of the CR20 mice had higher rectal temperatures than the corresponding CR40 mice, except for the D2 males (last blue bar in right graph), where CR20 and CR40 rectal temperatures were identical. Tellingly, those thermoregulation-impaired D2 males were the only strain / sex combination where CR20 didn't do at least as well as CR40 in terms of max lifespan (blue line in bottom right survival graph). Even there the survival advantage of CR40 relative to CR20 was small, and not statistically significant (see survival table), but it is nonetheless an interesting observation.

 

eIoA12g.png

 

What this shows is that the rectal temperature difference between CR20 and CR40 was positively correlated with survival - when CR20 mice were able to maintain a higher body temperature than CR40 mice, in all cases they lived as long, and generally lived longer, than CR40 mice.

 

This is completely congruous with the point I've been hammering away on in the Cold Exposure thread for many months now. Namely that remaining reasonably lean (but not too lean) while burning calories to stay warm in the face of cold exposure, is the right way to go, and in fact may be obligatory for CR benefits (as born out by the toastier, long-lived B6 CR20 mice of box sexes above). In fact, this thermogenesis-longevity link was so striking and apparent to me when I first read the study that I initially started posting about it to the CE thread, but quickly realized how important this study was for this thread as well. 

 

Further evidence in favor of the hypothesis that thermogenesis explains the longevity advantage of warm CR20 mice in this study comes from the adiponectin level data in the table I posted above. Notice the one group where adiponectin was higher in the CR20 mice than CR40 mice? That's right - in the longest-lived group in the entire study, the B6 females, who also had the highest rectal temperature. What's the connection between temperature and adiponectin? Cold exposure and brown adipose tissue activity elevates adiponectin not only in rodents, but also in humans. Here is the section on adiponectin and cold exposure from my CE Albatross post:

 

Adiponectin Production - Like CR [10], cold exposure increases adiponectin levels. Two hours of cold exposure resulted in a 70% increase in circulating adiponectin in adult men [36]. Study [8] found centenarians and their offspring had genetic mutations that boost adiponectin, and had higher circulating adiponectin, suggesting to the authors "their [i.e. adiponectin-promoting gene mutations] may promote increased lifespan through the regulation of adiponectin production and/or secretion." Study [35] found the same thing in a group of centenarian women - "As compared to BMI-matched [young, ~28 year-old] female controls, female centenarians had significantly higher plasma adiponectin concentrations. In addition, high concentrations of plasma adiponectin in centenarians was associated with favorable metabolic indicators, and with lower levels of C-reactive protein and E-selectin". For those of us who aren't lucky enough to have adiponectin-boosting genes, we can increase adiponectin levels via CR, cold exposure, or both. This video illustrates how wearing the Cool Fat Burner for two hours raises a cold-adapted person's adiponectin level by a whopping 62%!

 

Given how thorough these researchers were, it's really unfortunate and strange that they didn't measure tissue weights or gene expression in any tissues or organs other than the liver. it seems to me almost certain based on rectal temperature and adiponectin levels that the cases where the CR20 mice lived the longest were also the cases where they had the most (active) brown adipose tissue.

 

Interestingly, the authors recognized and addressed the correlation between body temperature (Tb) and longevity in their data, discussing it as follows. First they point out that Dr. Speakman (with all due respect) speaks out of both sides of his mouth (i.e. illogically, given his own data) regarding body temperature and the benefits of CR, as I've pointed out before. The authors of [1] put it charitably for Dr. S.:

 

Interestingly, strains of mice that maintain high Tb are more likely to have extended lifespan under CR (Speakman and Mitchell, 2011). While this is contradictory to the suggestion that lowered Tb is a contributing factor to lifespan extension under CR (Speakman and Mitchell, 2011), it certainly highlights that there is more complexity to the CR phenomenon, especially when performing comparisons across mouse strain and sex.

 

In other words, Speakman is just confused, and everyone but Michael (and perhaps Speakman, whose own data contradicts his assertion) realizes it's not just "calories, calories, calories". Instead, burning calories to maintain a higher body temperature is associated with extended, rather than shortened, lifespan.

 

But the authors clearly don't entirely understand their own data, and in particular their hot little, long-lived female B6 mice. While they recognize that the B6 females were exceptional among all their groups, not just for being the longest lived, but also for having a higher body temperature than either AL or CR40 mice, in fact higher than any other group of mice in their entire study:

 

Our findings are in concordance with previous studies [/size][that CR generally lowers body temperature - DP] [/size], with the exception of B6 female mice on CR. In these mice, [/size]Tb was significantly higher with 20% CR than in B6 females on AL or 40% CR.[/size]

 

but they miss the significance and the likely cause of this increased thermogenesis (namely increased BAT activity):

 

Alteration in heat production or heat loss and change in metabolic rate and/or activity could account for the increased Tb in B6 female mice on 20% CR.The preservation of fat mass means more insulation and lower rate of health decline as these mice age, which may have contributed in having opposing effects on the classical Tb response to CR (Rikke and Johnson, 2007). Even though metabolic rate and activity level were not measured, it is believed that lower Tb contributes to longevity through a direct effect on reducing pathologies (Speakman and Mitchell, 2011). 

 

Not only did they miss the connection between BAT/thermogenesis and longevity, this passage doesn't even make logical sense as a possible explanation for what they observed!

 

Sure, B6 females on CR20 carried some extra weight (likely at least part of which was fat) relative to the CR40 B6 females, and this extra fat may have contributed (minorly) to their ability to stay warmer. And sure, having a bit more meat on your bones can "lower [the] rate of health decline" in old age, as I've pointed out repeatedly in other threads. But this is very unlikely to be the whole explanation, since across the board the CR20 mice were heavier than the CR40 mice in this study, but it was only CR20 B6 females who lived dramatically longer, and were dramatically hotter, than either their AL or CR40 counterparts. Instead, it seems much more likely it was BAT thermogenesis that was the meaningful difference here.

 

Most inanely, the last sentence of the above passage seems to directly contract their own results. If "lower Tb contributes to longevity" why in heck did the hottest little B6 female CR20 mice live the longest of all the groups in their study? Hint: It's the BAT, stupid(s). 

 

But whether my Cold Exposure Hypothesis (summary - BAT and thermogenesis benefit longevity) is the explanation for why the CR20 groups lived at least as long and often longer than the CR40 groups in this study of (cool-housed) mice, or it's the more mundane explanation that adult-onset CR40 takes too much of a toll on the body, even when started gradually, or mostly likely, a combination of both explanations, one thing seems perfectly clear:

 

Once again we see an obesity-avoiding, mild CR regime is the "sweet spot" for CR benefits, and this is especially true when CR is started in adulthood, when serious CR may not only have no advantage relative to mild CR, it can be downright detrimental to lifespan.

 

I'm looking forward to seeing what responses (if any) defenders of the CR faith can come up with to explain (away) this one...

 

--Dean

 

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

[1] Cell Metab. 2016 Jun 14;23(6):1093-112. doi: 10.1016/j.cmet.2016.05.027.

 

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.

 

Mitchell SJ(1), Madrigal-Matute J(2), Scheibye-Knudsen M(3), Fang E(4), Aon M(5),

González-Reyes JA(6), Cortassa S(5), Kaushik S(2), Gonzalez-Freire M(1), Patel

B(2), Wahl D(1), Ali A(1), Calvo-Rubio M(6), Burón MI(6), Guiterrez V(1), Ward

TM(1), Palacios HH(1), Cai H(7), Frederick DW(8), Hine C(9), Broeskamp F(10),

Habering L(10), Dawson J(11), Beasley TM(11), Wan J(12), Ikeno Y(13), Hubbard

G(13), Becker KG(14), Zhang Y(14), Bohr VA(4), Longo DL(14), Navas P(15),

Ferrucci L(1), Sinclair DA(16), Cohen P(12), Egan JM(7), Mitchell JR(9), Baur

JA(8), Allison DB(11), Anson RM(1), Villalba JM(6), Madeo F(10), Cuervo AM(2),

Pearson KJ(17), Ingram DK(18), Bernier M(1), de Cabo R(19).

 

Free full text: http://www.sciencedirect.com/science/article/pii/S1550413116302492

 

Calorie restriction (CR) is the most robust non-genetic intervention to delay

aging. However, there are a number of emerging experimental variables that alter 

CR responses. We investigated the role of sex, strain, and level of CR on health 

and survival in mice. CR did not always correlate with lifespan extension,

although it consistently improved health across strains and sexes.

Transcriptional and metabolomics changes driven by CR in liver indicated

anaplerotic filling of the Krebs cycle together with fatty acid fueling of

mitochondria. CR prevented age-associated decline in the liver proteostasis

network while increasing mitochondrial number, preserving mitochondrial

ultrastructure and function with age. Abrogation of mitochondrial function

negated life-prolonging effects of CR in yeast and worms. Our data illustrate the

complexity of CR in the context of aging, with a clear separation of outcomes

related to health and survival, highlighting complexities of translation of CR

into human interventions.

 

Published by Elsevier Inc.

 

PMID: 27304509

 

----------

[2] J Nutr. 1986 Apr;116(4):641-54.

 

The retardation of aging in mice by dietary restriction: longevity, cancer,

immunity and lifetime energy intake.

 

Weindruch R, Walford RL, Fligiel S, Guthrie D.

 

Full text: http://sci-hub.cc/http://jn.nutrition.org/content/116/4/641.long

 

We sought to clarify the impact of dietary restriction (undernutrition without

malnutrition) on aging. Female mice from a long-lived strain were fed after

weaning in one of six ways: group 1) a nonpurified diet ad libitum; 2) 85 kcal/wk

of a purified diet (approximately 25% restriction); 3) 50 kcal/wk of a restricted

purified diet enriched in protein, vitamin and mineral content to provide nearly 

equal intakes of these essentials as in group 2 (approximately 55% restriction); 

4) as per group 3, but also restricted before weaning; 5) 50 kcal/wk of a

vitamin- and mineral-enriched diet but with protein intake gradually reduced over

the life span; 6) 40 kcal/wk of the diet fed to groups 3 and 4 (approximately 65%

restriction). Mice from groups 3-6 exhibited mean and maximal life spans 35-65%

greater than for group 1 and 20-40% greater than for group 2. Mice from group 6

lived longest of all. The longest lived 10% of mice from group 6 averaged 53.0 mo

which, to our knowledge, exceeds reported values for any mice of any strain.

Beneficial influences on tumor patterns and on declines with age in T-lymphocyte 

proliferation were most striking in group 6. Significant positive correlations

between adult body weight and longevity occurred in groups 3-5 suggesting that

increased metabolic efficiency may be related to longevity in restricted mice.

Mice from groups 3-6 ate approximately 30% more calories per gram of mouse over

the life span than did mice from group 2. These findings show the profound

anti-aging effects of dietary restriction and provide new information for

optimizing restriction regimes.

 

PMID: 3958810

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All,

 

While waiting hopefully and with bated breath for responses to my post above, I did a short summary of my interpretation of the new study (PMID 27304509), highlighting the cold exposure & thermogenesis angle, over on the Cold Exposure Thread.

 

Anyone who is interested in cold exposure and how thermogenesis might be an explanation for the rather surprising data in the study might want to check it out.

 

--Dean

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At the risk of sounding like a bragger I came to this conclusion a long time ago, posted my reservations about it, and drifted away. I read the forums more out of curiosity now Once a week or so. Dean remains highly interesting to read.

 

Dean you recently remarked to Saul that meat eaters were selfish and petty. That is true enough, but this list and all the efforts of trying to squeeze a few years of life exemplifies our innate selfishness and pettiness. So even the vegans here are self absorbed and petty. I include myself in this criticism.

 

We are humans and based on our wiring we must be intensely selfish, like it or not. Otherwise we would have died out. However I like to think and hope that there may be something we are missing and that scientific determinism will not prevail. It is already shaken by quantum conundrums like locality and uncertainty issues related to the observer effect. Time and space may not be what the determinist insist upon. As you say, paradigms generally hold fast as long as the committed elites who have invested their careers/egos on the current position hang around.

 

My point is this, rather than devoting all of this energy to surviving for an extra year or so, maybe it would be better spent on dare I say it-the meaning of living or life. After all we are capable, unlike all other life forms as far as we know, of seeing into ourselves and even perhaps transcending our selfish, petty nature! Perhaps that is something worth pursuing and devoting our utmost energies. Of course, loving and caring for ourselves is a virtue and feeding our bodies well, exercising etc. Is not to be condemned nor is discussing these issues, but there is a point where it does become a bit ridiculous I think.

Edited by mikeccolella

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Mike,

 

At the risk of sounding like a bragger I came to this conclusion [presumably, that serious CR won't beat a HOADL] a long time ago, posted my reservations about it, and drifted away. 

 

Congratulations Mike. You were far ahead of many of the rest of us. I'm glad you've stuck around, even though I picked on you (somewhat unfairly, since you redacted it from your post) as well as Saul for your omnivorous ways. 

 

...even the vegans here are self absorbed and petty. I include myself in this criticism.

 

There is a difference between self-interested, selfish, and "self-absorbed and petty". As you point out, being self-interested is inevitable - it's baked into our nature by evolution. I'm as self-interested as the next guy (or gal). IMO such an attitude becomes selfish and "self-absorbed and petty" when we chose to put our own trivial self-interests ahead of the welfare of other sentient creatures.  That is what makes eating meat unconscionable from my perspective.

 

However I like to think and hope that there may be something we are missing and that scientific determinism will not prevail.

 

I love the thought-provoking ideas in this quote and the rest of your post.  I'm going to finish this reply over here, where it seems more appropriate, where we can "let our hair down" (this is the CR Science & Theory Forum, after all), and where you and I have engaged in these kinds of discussions before. I hope you (and others) will follow and continue the discussion over there.

 

--Dean

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I've been on an extended (8000 mile) epic road trip across America, seeing some of the most amazing sights our country has to offer.  Finally getting back to "normal".  I've enjoyed catching up on some of the newer content including this thread.  Recently I've been turned on to "Quora" mostly because of the odd & fascinating tangents it seems to send me down once I start reading an answer - but I love its "upvote" system and seemingly heavy participation from various experts.   At any rate, I found a "quora" related to this thread:  Does calorie restriction extend life in humans? that you might be interested in, even Aubrey De Grey chimes in...  the reason I post this is because I see even in this very thread there are still people that seem to give too much credit to CR "mythology" - I am referring to the comments/quotes along the lines of "if it doesn't work in humans we must be pretty unique" or "what about all those 1000's of studies out there showing that it works?".  CR doesn't even work in most mice!  And as Dean has adeptly pointed out, when it DOES work, there is probably a very important connection with BAT/thermogenesis that should not be ignored or dismissed.  

 

I've stated elsewhere, but when I'm trying to help someone that wants to be healthier, I always just steer them toward the plant based whole food diet, no need to even discuss calories.  If they ask for more info, I send them the Kaiser Permanente guide to plant based diets.  If they are even more serious, I tell them about time restricted feeding (tRF).  Its extremely difficult for an overweight person NOT to lose weight lots of weight on a plant based diet, so just let it happen and let them get excited and happy about it.

Edited by Gordo

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All,

 

Since this thread is a clearinghouse for evidence regarding the question of whether or not serious CR will beat a healthy, obesity-avoiding diet and lifestyle, I figured it's worth pointing to other recent threads / posts on the forums that are relevant to this question.

 

So here are a few - with a brief summary of each:

  • Optimal BMI - Meta-analysis of studies involving 4 million healthy non-smokers that found a BMI of 22-24 was optimal for longevity, and that excluding early years of followup (to prevent penalizing low BMIs for sick thin people), made only a minor difference and did not change the fact that a BMI less than 21 was always worse than a BMI in the 21-25 range when it came to longevity. Low BMI was particularly detrimental in men.
  • Eat More and Do More to Live More - Study of the NHANES folks over 60yo found that 1) people who ate the most, lived the longest, and 2) people who were most active lived the longest, and 3) people who ate the most and were most active lived longest of all.
  • CALERIE Study - In an randomized control intervention of CR in middle-aged, healthy people (by Luigi), very modest (9% CR over 2 years) was sufficient to induce modest weight loss (BMI 25 → 22.5), reduce markers of inflammation without compromising immunocompetence.
  • Impaired Glucose Tolerance - A discussion of the likely mechanism(s) by which serious CR results in impaired glucose tolerance in people. It could be serious CR trashes the pancreas so that it can't / won't release enough insulin to cope with post-meal glucose. But it is likely also a result of having too little muscle mass and/or (healthy brown) fat mass to serve as a sink for the glucose (see here for discussion of how BAT serves a glucose sink). Other recent discussion of the problem, and potential solutions.

 

Those are all the places I can think of (besides this thread) where we've recently discussed the relative merits / dangers of serious CR vs. a healthy, obesity-avoiding diet and lifestyle.

 

--Dean

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I've been on an extended (8000 mile) epic road trip across America, seeing some of the most amazing sights our country has to offer.

Wow, hey, congratulations on travelling -- always good for the soul, I feel, as long as travelling remains whimsical and not just "for work" and paying the man. This country is so beautiful -- I love America -- the US, Mexico, and Canada have so much natural physical beauty and friendly people -- I'm happy you're able to appreciate!

 

...the reason I post this is because I see even in this very thread there are still people that seem to give too much credit to CR "mythology" - I am referring to the comments/quotes along the lines of "if it doesn't work in humans we must be pretty unique" or "what about all those 1000's of studies out there showing that it works?"

I guess my response to this is yes, I agree, but what other choices do we have to slow aging? Sure CR probably doesn't work to extend lifespan in people; but it's not like we're brimming to overflow with any other options, right? Maybe if we did have other ways to slow, stop, or reverse aging we'd all drop this annoying CR business and eagerly pick up whatever.

 

But so far: nothing. Nothing works better here in good ole 2016 to prolong healthspan than CR. And maybe not even that. Being perpetually cold seems like a really cruel option -- but maybe that's what we puritanicals require in order to prolong lifespan? Suffering not just hunger, but also shivering with cold misery? Suffer ye seekers...

 

Wow, so if all here is like a computer simulation (or whatever Dean is saying) then it looks to me like these giant cosmic scientists studying us poor schmucks are just as cruel and unusual to us humans as we are cruel and awful to the poor animals we must study in our own useless experiments.

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"I guess my response to this is yes, I agree, but what other choices do we have to slow aging? "

 

A healthy obesity avoiding diet would be the primary current choice. CE another. There are LOTs of interesting things coming down the pipeline, immediately or very soon, and countless others will follow. Perhaps one of the most important roles these forums could play is to just keep track of everything IN the pipeline.  Some things I've been reading about recently along these lines:

 

 


 

(I am captivated by CRISPR, can't wait for the future when anyone can play with this tech)


 

Numerous new ways of removing senescent cells are in the pipeline, and this will undoubtedly lead to longer lifespans.


 

I'm skeptical of the following, but Rory Blake claims only a pending patent is keeping his product "proven to halt aging" (I'd love to see this proof in the form of a clinical trial published in a reputable peer reviewed journal) from being on the market already (I think his nutritional theory of aging is an oversimplification but may be a small piece of the puzzle).

 

And of course there are always going to be mad scientists doing crazy things that may one day prove useful, like getting a whole new body when the first one wears out. Along similar lines, the singularity/rise of machine intelligence may ultimately be what it takes to crack what I believe to be the very solvable problem of aging.  Sometimes I wonder why I'm still writing software for "big pharma" instead of software for "big picture".

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Perhaps one of the most important roles these forums could play is to just keep track of everything IN the pipeline.

 

Good idea. It's hard for lay people to know what's going on in these labs, what's under development in startup companies, and how to separate hype from non-fiction prose.

 

Danger: more Sthira rant ahead :-(

 

It's annoying how big promises suddenly jolt forward, and only a few days later are eclipsed by more sudden wordy jolts. We hear great promises, then they disappear, then new great promises appear, then they're replaced by more, others, over and over. Hey, after enough of these (what feels to a lay person, non-scientist like I) empty promises these breathless announcements begin to feel like teases.

 

I signed up for a Harvard Med School newsletter health living word mess -- why oh why bother -- and these writers are still talking about the evils of trans fats and saturated fats and go get ya some good sunshine but be sure to cover up cancer prone skin with hats and chemicals and hide in the shade, and be sure to cultivate positive healthy relationships (with obese crazy people half-strung on pharmaceuticals, I guess?). Wear my bike helmet: thanks, Harvard; eat more brightly colored f&v: thanks, Harvard; don't club and do drugs: thanks, Harvard; go to church: thanks, Jesus C. Harvard, what is this fucking 1950?

 

Meanwhile, I read that for Greg Fahy's group "...The fundamentals (of thymus-based regen) were proven in 1990, and have been verified to work in many preclinical animal models, yet no one has chosen to apply this method to human patients. We think this lack of clinical application is egregious, and we intend to overcome it by carrying out the first clinical trial of intrathymic islet transplantation for the cure of type 1 diabetes in human patients..."

 

http://interveneimmune.com/?p=1125

 

What is going on in labs, what is under development in startups, and how do we find out? Yakking on and on about purifying diet and lifestyle is fun, entertaining, sometimes useful but it isn't helping repair the damages caused by aging.

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 Perhaps one of the most important roles these forums could play is to just keep track of everything IN the pipeline.

Good idea. It's hard for lay people to know what's going on in these labs, what's under development in startup companies, and how to separate hype from non-fiction prose.

 

I agree - that is a good idea. While I'm pretty skeptical of most of the developments Gordo has outlined (along with Liz Parrish's telomerase + myostatin gene therapy, Elysium's NAD+ boosting supplement blend, etc.) it's exciting to watch and keep tabs on them. It's like a cambrian explosion of anti-aging interventions. Yes Sthira, most of them don't / won't amount to much (including human CR ☹), but maybe one or two of them will.

 

Imagine the alternative. Imagine we lived in the middle ages, where there was absolutely no hope of a scientific route to immortality. We're fortunate to live at a time when we can legitimately harbor hope (however small) of living indefinitely. So don't be too discouraged, bitter or resentful about the slow progress, unless it prompts you to do something about it. Instead, like the rest of us, do your best to keep healthy through safe, mostly natural, common-sense methods for now, and keep your eyes peeled for interventions that might prove effective at giving us many more years. 

 

Danger: more Sthira rant ahead :-(

 

Rant away Sthira. I can certainly share your feeling of frustration. In some ways, the medievals who knew they were going to die, no ifs ands or buts about it, had it better than us, since they had one less thing to worry about, and to cry out in frustration about - "where is that damn immortality pill they've been promising us!". Today, indefinite lifespan sometimes feels so close we can taste it. But alas, that is probably an illusion. The harder we look, the more complicated the body, and the aging process, appear to be. There probably are no low-hanging fruit or silver bullets when it comes to delaying aging significantly, otherwise nature would have found and exploited them already. I think Aubrey & co are on the right track with their engineering approach to repairing damage. Sadly, they are probably far too optimistic about the timeline.

 

But if you allow for the possibility of whole body cryopreservation / vitrification to give the smart scientists a couple more centuries to figure it all out, I think there is a non-zero chance that indefinite lifespan will happen for people alive today.

 

--Dean

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You might say that I am one of those severe chronic CR injured war veterans that Dean talks about.  Below is my recent X-ray exam report and are previous X-ray reports of my lungs and vertebra.  But, I was surprised that the current report did not say I have osteoporosis, only osteopenia.  Maybe it is because it is a different lab and radiologist exam.

 

Re how do I feel about my health, with what I have done to myself, it is fortunate that I am alive, but it could have been worse.  I take no medicines, whereas my siblings and mother do and father did.  I have not died from cancer like my 2é6 siblings.  I have not required a stent in my heart due to 90 percent block of my coronary artery like my 18-month older brother or had a heart attack like my younger brother, nor his pancreatitis, apparently from his diet.

 

I wonder if it might be expedient to have one of those surveys Dean initiates, this one comparing the health of those of us who CR with our siblings.  These data might highlight our health compared with genetically related people.

 

Re a healthy obesity-avoiding diet and lifestyle, and its application especially in the elderly, the other thing is whether things such as intermittent fasting also benefits elderly folks.


Al Pater 27/6/16 X-ray report:
X-ray radiologist report
CERVICAL SPINE
    Visualization is obtained to C7 with cervicothoracic junction poorly visualized.  There is a slightly exaggerated cervical lordosis.  There is moderate narrowing of the C5-6 disc space.  Vertebral body heights are maintained.  Bones appear somewhat osteopenic.  No prevertebral soft tissue swelling.
THORACIC SPINE
    There is levoconvex scoliosis of the upper thoracic spine but fairly marked kyphosis.  There are numerous compression fractures of the thoracic spine, essentially involving every level to some degree, with the exception of perhaps the superior most thoracic vertebra.  The bones are osteopenic.  I suspect old rib fractures, though those are not well evaluated on these limited views.
LUMBAR SPINE
    Bones ore osteopenic and it is difficult to determine how many lumbar vertebral bodies there are.  A mild dextroconvex curve is noted.  Again, there are compression fractures of multiple lumbar vertebra, I believe L1-5 in particular.  There is moderate posterior disc space narrowing, which may relate to back extension in part.  

18/01/13  My X-rays showed:
FINDINGS: Comparison: Oct ‘09
The heart is not enlarged.  There is some chronic volume loss in the right middle lobe.  The lungs are otherwise clear apart from scarring of the apices.  The nodule seen in the right upper lung zone previously is not apparent today.
The bones are markedly osteoporotic and there are multiple compression deformities in the thoracic spine giving rise to an increased dorsal kyphosis.  These have progressed since October ’09.
====================================================

08/10/09 X-rays.
FINDINGS: The heart is not enlarged.  Streaky opacities are again present in the right middle lobe but recent CR revealed http://en.wikipedia.org/wiki/Atelectasisand http://en.wikipedia.org/wiki/Bronchiectasis in this area and this would account for the finding.  No definite pneumonia demonstrated.
Patient has developed a small nodule in the right upper lung zone, measuring 13m mm in diameter.  It may overlie the aortic arch on the lateral view.  I cannot identify it on the previous exam.  CT suggested for further assessment.
There are multiple compression deformities in the thoracic spine and increased dorsal kyphosis is noted.
IMPRESSION:  http://en.wikipedia.org/wiki/Bronchiectasisin the right middle lobe as seen on CR.  No definite pneumonia.
             Nodule in the right upper lung zone.  CT is suggested.

Aug 11, 2008 CT scan of chest and abdomen
Known liver http://en.wikipedia.org/wiki/Hemangioma
Mild to moderate left and tiny right http://en.wikipedia.org/wiki/Pleural_effusionis noted.  There is also mild to moderate ascites as well as generalized increased density with the visualized subcutaneous fat.
http://en.wikipedia.org/wiki/Bronchiectasisand http://en.wikipedia.org/wiki/Atelectasis is noted within the right middle lobe.  Bilateral apical scarring is seen.  There is left greater than right lower lobe atelectasis.
Some debris is noted within the distal trachea which is presumably mucosal secretion.
The bones are demineralized and there is loss of height of several thoracic vertebral bodies with accentuation of the thoracic kyphosis.  No convincing lymphadenopathy.
A 10 mm nodular lesion is present within the right lobe of the liver (segment VII centrally).  This demonstrates some globular peripheral enhancement and is likely a hemangioma.  No other focal liver lesion identified
Nonobstructing 8 x 4 mm calculus is present within the lower pole of the right kidney.  [http://www.ncbi.nlm.nih.gov/pubmed/25463995kidney stone] The left kidney is unremarkable.
Incidental infrarenal left IVC is noted.
IMPRESSION:
1.  Left greater than right pleural effusions and ascites of uncertain origin.  Right middle lobe atelectasis and bronchiectasis with biapical scarring which is presumably chronic.
2.  A 10 mm lesion centrally within segment VII of the liver would be most compatible with a hemangioma.
3.  Nonobstructing 8 x 4 mm right lower pole renal calculus.

An Oct. 27, 2007 chest X-ray report said:
Exam:  WC chest two views
Compared to Oct.'07
Right middle lobe consolidation continues to progress.  There is now more involvement in the lateral segment.  If antibiotic coverage is considered adequate, perhaps further assessment with bronchoscopy is indicated.

15/9/06 X-ray
     "Exam:  WC CHEST TWO VIEWS
     Compared to previous Oct, 2005.
     The patient has developed another significant compression fracture in one of the mid-thoracic vertebrae at the junction of the mid and lower thirds with about 60% loss of height anteriorly.  This is resulting in a more increased dorsal kyphosis.
     There is some persistent volume loss in the right middle lobe which is unaltered since the previous examination.  The lungs are otherwise clear."

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Al,

 

It is good that you are still with us. Around the mid-2000s, I was quite worried you weren't long for this earth.

 

I always have trouble reading your posts with your biometrics and blood tests. Are there any insights you can share about what (if anything) you changed as a result of the health challenges (osteoporosis, pneumonia) you experienced back then, that may have helped you get to where you are now? Or alternatively, what you might have done differently back then knowing what you know now?

 

--Dean

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I didn't see it mentioned in this thread, or elsewhere in the forums, but I just stumbled upon a recent BLOG (not video)  post from Dr. Greger related to this topic where he takes a little shot at CR:

 

 

Caloric Restriction vs. Plant-Based Diets

Written by: Michael Greger M.D. 

on July 14th, 2016

 

"Researchers recruited vegans from the St. Louis Vegetarian Society, and went to the Calorie Restriction Society to find folks practicing severe caloric restriction. What did they find?Only the vegan group got a significant drop in IGF-1. These findings demonstrate that, unlike in rodents, long-term severe caloric restriction in humans does not reduce the level of this cancer-promoting hormone. It’s not how many calories we eat, but the protein intake that may be the key determinant of circulating IGF-1 levels in humans; and so, reduced protein intake may become an important component of anti-cancer and anti-aging dietary interventions."

 

I know there are lots of Greger critics here and elsewhere, but I think he has a point in this case although I don't even think its fair to blame "protein" in general, its specific sources of protein that contain the amino acids that boost IGF-1, namely animal protein (and some vegan sources as well like seaweed/spirulina).  I'm not sure what CRS members were tested for the above referenced study, but this goes back to the idea of there not really being any particular "standard" or even definition for what CR is.  By my definition all of the St. Louis Vegetarian Society members were probably also practicing CR (assuming they consume fewer calories than the average american of their height and gender).

Edited by Gordo

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All:
 

I didn't see it mentioned in this thread, or elsewhere in the forums

 

Did you use the search ;) ?
 

, but I just stumbled upon a recent BLOG (not video)  post from Dr. Greger related to this topic where he takes a little shot at CR:
 
 
I know there are lots of Greger critics here and elsewhere, but I think he has a point in this case although I don't even think its fair to blame "protein" in general, its specific sources of protein that contain the amino acids that boost IGF-1, namely animal protein (and some vegan sources as well like seaweed/spirulina). 


There's a tiny point in there, which he then misrepresents for the sake of advancing a predetermined agenda. See Dean's gentle takedown here, and his previous takedown of Greger making the same pseudo-point based on the same misrepresentation of the same study here.

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Type "Caloric Restriction vs. Plant Based Diets" or the URL to the article or even part of the URL into the search box, the only thing that comes up is my post above ;)

Also both of your links pre-date Gregers post so they aren't a response to it, although I guess they are related, I'll check that out, thanks.

 

EDIT to say: Yea, I see now Greger just "recycled" some older material he had written and gave it a new title (lame).  And I think I was just searching this thread instead of all threads (my mistake).

Edited by Gordo

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Michael wrote: 

See Dean's gentle takedown here, and his previous takedown of Greger making the same pseudo-point based on the same misrepresentation of the same study here.

 

Thanks Michael!

 

Nice to see you aren't hold too much of a grudge over my recent (unwarranted) personal gibes (not jibes or jives!). For once we seem to be in agreement. 

 

Dr. Greger was playing a bit fast and loose using Luigi's IGF-1 study of you, me and other CR folks. In particular, he made it seem it that the study suggested reducing IGF-1 required reducing consumption of animal protein, when the best interpretation of the study was simply that reducing total protein was sufficient to lower IGF-1.

 

I still think it's pretty clear from other studies though that there is an advantage to getting one's protein from plants rather than animals, as the new JAMA study (discussed here) suggests, as well as the study discussed here. But it may not be the animal protein per se but the other bad things that come with animal products (saturated fat, cholesterol, trans fats, TMAO-boosting choline & carnitine, endotoxins, PCBs & other pesticides, mercury, arsenic, parasites, etc.) that are most detrimental.

 

I think this is something else we can agree on, namely it doesn't make much sense to focus on individual nutrients (e.g. animal protein) rather than whole foods, which come as complete packages.

 

But while I've got your ear, I'd love it and I know other would as well if you could tell us your thoughts about the recent sucralose / artificial sweetener study, which really has me scratching my head.

 

--Dean

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Type "Caloric Restriction vs. Plant Based Diets" or the URL to the article or even part of the URL into the search box, the only thing that comes up is my post above ;)

Hm. Were you mistakenly (self-recursively) searching "this topic"? When I do that search, I get yours, and also this. (It's best to always use the advanced search IAC).

 

But, IAC: simply searching by a title or headline is not likely to to get you good search results (though it works fine in this case). recalling these previous instances, I searched "fontana greger IGF-1" (no quotes). And I selected to see posts rather than threads to avoid having to wade thru' them.

 

Also both of your links pre-date Gregers post so they aren't a response to it, although I guess they are related, I'll check that out, thanks.

Sorry: I mis-linked that first one. I meant (again) to link to this, which is exactly about the Greger "Caloric Restriction vs. Plant Based Diets" blog post.

 

EDIT to say: Yea, I see now Greger just "recycled" some older material he had written and gave it a new title (lame).

In one of them, yes. But the real problem isn't the recycling, since the two were on slightly different overall topics, but the misrepresentation of the findings.

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From the old CR Society homepage:

 

Since the 1930s extensive scientific research has shown that calorie restricted (CR) diets improve health and extend lifespans of nearly every species tested, including worms, spiders, rodents, dogs, cows and monkeys. 

 

As discussed earlier in this thread, we can cross out dogs and monkeys from the list of species where CR has been shown to work, and we should put a big question mark next to rodents as well, at least compared with a healthy, obesity-avoiding diet and lifestyle. Now we can scratch off cows too.  Worms seem pretty safe though, and hopefully we can hold the line at spiders...

 

--Dean

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