Motivation for Practicing CR?

The Observer · August 29, 2016

[Admin Note: Observer (the OP) and others - I apologize for moving this post around. After (nearly) completing a long response, I realize just how interesting Observer's questions are, and how they deserve their own thread in the CR Practice Forum. Thanks Observer! I'll be posting a detailed response shortly. - Dean]

Great, now you guys somewhat discouraged me in throughout this thread. Just when I was getting a little bit more serious about starting a proper CR regime, after ~10 years of hesitation. :angry:

But now you convinced me CR probably doesn't do much for us humans, compared to just eating/exercising healthy and staying slim. I am currently on some mild-CR plan with one 24-hour fast every week and my BMI is 21.5. Was planning on lowering it down do 19-20, but now I don't see a reason for doing it anymore. :(

Before I believed I would gain at least 5-8 additional years, especially because of my own anecdotal evidence. I am somewhat a unique human specieman in that I was basically on CR for most of my life, unknowingly.. I simply rejected food, never liked sweets and was always semi-anorexic. As a result (I guess) I was developing slower as a child and always looked much younger than my peers. Even now in my late 30's people think I look 25-30 and I do agree my biological age must be closer to 30. Then again, what do I know?

Now reading your posts Dean, you seem like a reasonable individual and you convinced me that we probably cannot gain more than ~2 years through CR and possibly even shorten our lifespan.. So the obvious question is, why do you - and others - even continue practicing it? Why not simply live healthy lives?

I'm thinking perhaps I should only concentrate on fasting and autophagy that comes with it? What are your thoughts on that Dean, if you don't mind answering?

Dean Pomerleau · August 30, 2016

Welcome Observer!

First off - Thanks for posting. You'll notice that I've shifted your post from the Dean's Current Diet thread to this one, since your questions and perspective seem much more about motivation / rationale for practicing CR, and if so how severe CR to practice, rather than about what particular foods I or other CR folks are eating these days.

Now reading your posts Dean, you seem like a reasonable individual and you convinced me that we probably cannot gain more than ~2 years through CR and possibly even shorten our lifespan...

Thanks for the vote of confidence Observer. You've fairly characterized my current perspective, but before going further, I want to point out something that may be important.

Those of us who are in our late 40s and 50s, and even (perhaps especially) youngsters like yourself (late 30s), are likely to be on cusp of a revolution in aging over the coming decades. As a result, small changes in our healthspan and lifespan could get amplified, potentially even putting us on one side or the other of "longevity escape velocity". For example, it's possible and extra 2 years of healthy lifespan that CR might provide could get amplified to 10 years as a result of healthcare breakthroughs, which might buy us time to benefit from SENS cleanup and repair therapies, which would buy us even more time, etc.

In short, if you've got the discipline and motivation, even something that ostensibly might appear today to gains you only 2 years might ultimately be very worth pursuing.

But having said that, my skepticism goes deeper than just how many extra years CR is likely to provide. My skepticism stems from my increasingly strong conviction that CR may not provide any additional benefits for humans relatively to a healthy, obesity-avoiding diet, and in fact may even be detrimental to health and lifespan, particularly if pursued too aggressively, and for too long into one's elder years. I won't rehash all the evidence on which I base my perspective. I've been harping on it enough (incessantly?) lately, and the text and tone of your post shows you have clearly heard the message.

Given my skepticism, you pose a really insightful question:

So the obvious question is, why do you - and others - even continue practicing it? Why not simply live healthy lives?

I won't try to answer for others, and I hope they (and you) won't take my response as the ultimate answer, but instead will chime in with their own perspective. But I share the following list of possible motivations as a discussion starter. I'd love to hear what other CR folks think about this list of motivations below, and any I've missed.

Introspecting and after talking with people at the CR conference, I think the hardcore CR folks (of which I was one up until relatively recently, which I roughly characterize as people who've been practicing for > 5 years with a BMI < 19), have quite a few different reasons for their continued diligent practice of serious CR, some explicitly held and some more implicit. Below is a list I came up in the order they came to mind. They are not mutually exclusive - I expect most serious CR folks subscribe to several of these to varying degrees, and the subset will depend on their priorities and the severity of their CR practice:

CR Optimism - Continued optimism that the CR primate studies were a fluke, and that the rodent CR results will scale directly to humans (i.e. 20-40% extension of remaining lifespan = 10-20 human years).
Longevity Amplification - The amplification effect discussed above which might turn a small (e.g. 2 year) life extension into something much larger.
Healthspan Extension - even if CR doesn't add extra years, it will keep us healthier during the years we've got.
Physical Benefits - We like the way CR makes us feel here and now, including things like increased energy, stamina, heat tolerance etc., regardless of what it does for our long-term health and longevity.
Appearance Benefits - Some people are happier with the way they look practicing CR. Obviously this one will depend on the severity of one's CR practice, and the weight one starts at.
Psychological Benefits - While I and others have come to question the lifespan benefits of CR relative to a healthy, obesity-avoiding diet, many of us (including myself) have always appreciated the "calm abiding" demeanor and outlook on life that long-term, serious CR seems to evoke, perhaps as a result of reduced testosterone. I hesitate to point to it, since parts are quite personal, but there is an entire thread about the topic of CR's effects on the psyche and personality, called CR Psychology - The Good, the Bad and the Ugly.
Self and Others' Perception - We've built an identity around our practice of CR, both in our own eyes, and in the eyes of friends/families/colleagues. That, coupled with the reputation we've fostered as being smart and hyper-rational, makes it hard to acknowledge we may have been mistaken, particularly when friends, family and colleagues would love to be able to say "I told you so", when/if we back away from our practice of serious CR. If we back off, we fear we'll either be viewed as having caved, and therefore are weak-willed just like everybody else, or perhaps worse, as having been wrong, which nobody likes to admit to themselves or to others.
Habit - Many of us are creatures of habit, and habits are hard to break. Momentum keeps us going with our practice of CR, even when we sneaking suspicion that it may not be serving us (any longer).
Sunk Costs - We figure we've been practicing CR for so long that whatever damage (if there is any damage) to our physical body and to our social relationships has already been done, and so we might as well stick it out at this point, in hopes it will pay off.
Uniqueness / Exploration - We enjoy being different, or believe there is genuine value in exploring new possibilities, and pushing the envelope of human potential.

I personally went through in my head and ranked/rated these ten motivations for myself, and I'm really curious to hear how important others consider each of them to be for their own practice. In fact, I'm so curious that I've made it easy for people to share their rankings/ratings via a brief survey.

Please everyone, take a few moments now, before reading further, to complete this short Survey of CR Motivations.

I'll summarize the survey results in a couple days, and share my own ranking and the reasoning behind it. I hope it will foster some good discussion. But for now I'm not going to share my ranking to avoid biasing other people's responses.

Instead and in the meantime, I'll try to address your questions rather indirectly Observer:

So the obvious question is, why do you - and others - even continue practicing it? Why not simply live healthy lives?

by discussing briefly the changes I've made to my CR practice relatively recently, based on my evolving perception of the benefits of CR vs. a healthy, obesity-avoiding diet.

As you've obviously seen, I've grown pretty skeptical about whether CR will beat a healthy, obesity-avoiding diet and lifestyle. So I've switched to a what I've come to call "net calorie restriction" (a term that probably really grates on a few people...) - in which I eat lots of extremely healthy calories, virtually ad lib in fact, but only once per day within a 2 hour window to avoid overeating and to gain the benefits of time-restricted feeding (e.g. as discussed here). I also engage in nearly continuous moderate, low-impact exercise and cold exposure to create a net calorie shortfall, which I've argued is what matters for CR benefits.

But so as not to be a hypocrite, and urr, put my calories where my mouth is ☺, I've also increased my net energy balance, resulting in intentional weight gain. As you can see from the graph of my weight over the last year, I've gone from a nadir of around 115 lbs last fall (BMI 17.2, I'm 5'8.5") to my current weight of around 129 (BMI 19.3). This is the weight I'm targeting (for now at least), illustrated by the weight plateau during the last month which included my recent vacation:

I'm pretty happy with the results.

Objectively, my postprandial glucose has never been better (discussed here too), and my latest blood tests appear to still be showing the hallmarks of being the "CR Zone". Subjectively, I feel like I'm firing on all cylinders, both physically and mentally in a way I've never felt in my previous 15 years of practicing absolute (vs net) CR.

Psychologically, I'm happy to report that backing off the severity of my CR and practicing net rather than absolute calorie restriction has preserved what I consider to be the best part of CR-induced psychological changes (in particular that "calm abiding" feeling), while also providing me greater energy and a zest for life. How else could I continue to post so incessantly and optimistically to these forums ☺.

So the short answer to your question:

...why do you - and others - even continue practicing it? Why not simply live healthy lives?

is that some would say I'm not practicing CR (at least in the traditional sense) anymore. Instead I'm trying to live a healthy life by eating quite a bit (some would say stupid high amounts, here too, which I take to be groundless hyperbole) of healthy food, with a ton of exercise and cold exposure to stay lean and healthy.

Finally, Observer wrote:

I'm thinking perhaps I should only concentrate on fasting and autophagy that comes with it? What are your thoughts on that Dean, if you don't mind answering?

There do appear to me to be some benefits of intermittent fasting (i.e. ≥ 1 day), including autophagy. But sometimes autophagy isn't so great, and fasting causes your body to catabolize brown fat (bad news in my book), as opposed to my preferred practice, Time-restricted feeding (TRF), which boosts brown fat. As a result, I'm not convinced intermittent fasting will have the same benefits as TRF, and perhaps more importantly, as far as I can tell and last I knew, neither is Michael (added bashing here). Like me, it appears Michael does endorse TRF, or at least large time gaps between daily meals.

Welcome once again to the CR forums Observer!

--Dean

Michael R · September 2, 2016

Dean, and all:

Introspecting and after talking with people at the CR conference, I think the hardcore CR folks ... have quite a few different reasons for their continued diligent practice of serious CR ...

CR Optimism - Continued optimism that the CR primate studies were a fluke, and that the rodent CR results will scale directly to humans (i.e. 20-40% extension of remaining lifespan = 10-20 human years).

Dean, you're developing a habit of caricature which is not productive. The only person that I know who thinks something at least close to "that the CR primate studies were a fluke" is Saul, and he has explicitly said that he's not in it for the life extension anyway.

What I, for one, think is that, first, the UWisc study is not at all a fluke, but it's also non-evidentiary. If you take it as a CR study, it would be great news, showing substantial life extension (particularly when looking at age-related cauases of death) and dramatic anti-aging effects across multiple systems. The problem, of course, is that it's in retrospect not at all a CR study, but an obesity-and-junk-food-avoidance study, and therefore can only be presented at as evidence of the translatability of CR dishonestly, self-deludingly, ignorantly, or with extreme caution in specific findings.

Second, as discussed in extensive detail, and given even more striking weight by additional information revealed by Richard Miller at the last CR conference, the failure of the NIA study to demonstrate extended lifespan was also not a fluke, but was also inconclusive, first and foremost because of the combination of having been statistically underpowered from the outset to report a life extension outcome (that not having been its original intent) and the animals having been never much more than 20% CRed and not much more than 10% for most of the study — plus many other details, as discussed.

Dean Pomerleau · September 2, 2016

Michael,

You're developing habits of question-beggary and nitpickery which are not productive. ☺

The only person that I know who thinks something at least close to "that the CR primate studies were a fluke" is Saul, and he has explicitly said that he's not in it for the life extension anyway.

Saul hasn't spoken for himself or filled out the survey, so I can't say exactly what he thinks now, and we can debate about how rational or consistent Saul's views are. But I'll acknowledge that perhaps "fluke" was the wrong word to characterize Saul or anyone's perspective on the CR primate studies. But the fact is Saul has repeatedly criticized dismissal of the CR primate results as:

"ONE study. ... Single studies are of very limited use -- especially when they're small and not extremely carefully executed."

On this I agree with Saul and with you - the disappointing results of the CR primate studies may not be a good reason to dismiss human CR outright (due to methodological flaws), but neither are they any sort of evidence in favor of continued optimism or motivation for personal practice. But that doesn't stop some people... Rodney would be another such long-timer who seemed to be in the "CR Optimism" camp, suggesting recently that:

...restriction of calories is more important than everything else combined by, perhaps, nearly an order of magnitude...

But stepping back a moment from the particular words I chose to characterize the gist of the "CR Optimism" mindset, once again Michael you've missed the forest for the trees. Regardless of people's perspective on the monkey study results, I stand by my observation that "CR Optimism" is one possible motivation for some long-time CR practitioners continuing to practice, and as such is clearly worth including in a survey of this type, if for no other reason that to see how far optimism about human CR's life extension potential has fallen since those salad days of heady confidence, back when books with titles like Beyond the 120 Year Diet: How to Double Your Vital Years and programs like The 125 Year Plan didn't seems so naive.

And speaking of missing the point - not only did your post not address the topic of this thread (our personal motivations for continuing to practice CR), but you didn't even bother to fill out the 3-minute survey on CR Motivation, despite obviously having read my post about it. You and Al are two of the very few active (or at least semi-active) people around here who are still practicing serious CR. Al filled it out (thanks Al!) and gave some interesting responses, which I strongly encourage him to elaborate on in a post to this thread if he's willing.

Why the silence from you on your personal CR motivations? I think if there is anyone around here that people would really like to hear from about their motivation for continuing to practice severe CR, it would be you Michael.

Sadly, I suspect your message above will be another in your long line of "one and done" posts, and that this missive to engage with us in discussions about personal CR motivations will fall on deaf ears. That would (or will be) too bad, given how people (including me) look up to you, and given your leadership role in the CR Society, now that it's more visible leaders (Brian and Bob¹) have stepped away. I for one would really like to hear your perspective since we didn't get much of a chance to chat at the recent CR Conference.

--Dean

---------

¹Interesting Aside: Saul was also wrong about our in absentia Chairman of the Board (Bob Cavanaugh), who he predicted would win his bid for a seat in Congress, bringing CR advocacy to the national political stage. Bob didn't make the final republican primary ballot in his NC district, a fact that was public knowledge at the time Saul made his optimistic prediction in May. Probably just as well IMO, since Bob is the chairman of his local Tea Party chapter... But to his credit, Bob did talk up calorie restriction and his leadership role in the CRS as part of the experience and perspective he'd bring to Congress during his campaign in 2010, which also came up short. Perhaps it's no wonder he lost. But still I'm a bit surprised. At least back in 2010 his rhetoric sounded an awfully lot like someone else who has had frightening success in the public spotlight lately:

Current figures place the number of illegal aliens in the US between 12 and 20 million. From my travels around North Carolina, I would almost believe that there are 12 million in our State alone... It is imperative though that the physical US/Mexico border fence be completed as a national priority. I believe this would stem the flow of not only illegal aliens but it would also make a major impact on drug smuggling into this country. It would also limit the ability of terrorists to enter this country.

Better watch out. Next thing you know there'll be taco trucks on every corner. Sorry but I couldn't help pointing out a great example of rational priority setting in action...

Pea · September 2, 2016

Your survey and discussions remind me of Jonathan Haidt’s book “The Righteous Mind”.

Though the book is about “why good people are divided by politics and religion”, it is his explanation about what he considers to be a deeper awareness of decision making and human nature that appeals to me.

Like Hume’s notion that reason is slave to our passions, Haidt argues that people are fundamentally intuitive, rather than rational.

Using the metaphor of a rational rider atop an irrational elephant, (conscious intellect being the rider and gut instinct the elephant) Haidt claims the rider can only nudge the elephant in any one direction, but the elephant is ultimately the one in charge of where we wind up.

According to Haidt, people don’t really use their power of reason like judge or teacher, weighting evidence in order to make the best decisions. Instead, we more often than not, use reason to justify our decisions and actions.

What’s the “Motivation for Practicing CR?”

I think the survey is great and I like the well thought out questions. To use Haidt metaphor, why is the elephant taking us down the CR path?

Like this quote by Richard Feynman “Physics is like sex, it may give some practical results, but that’s not why we do it”.

I have been practicing a mild/moderate form of CR without realizing there is a whole community of folks doing this conscientiously. I have used various arguments to justify my actions to myself over the course of the last 20+ years. The justifications have changed, in part because advice about diet and exercise have changed (quite drastically!) but at least for me, I suspect the fact that I care so much about these things has a lot more to do with the elephant I am riding than it does with my conscious rational self.

-Pea

Dean Pomerleau · September 3, 2016

Pea,

Your survey and discussions remind me of Jonathan Haidt’s book “The Righteous Mind”.

I love Jonathan Haidt (not to mention David Hume). His investigation of "moral dumbfounding" never ceases to amuse and amaze me. I also think his characterization of the values stressed by conservatives vs liberals (video below), without the typical academic bias in favor of the later, is really refreshing.

Using the metaphor of a rational rider atop an irrational elephant, (conscious intellect being the rider and gut instinct the elephant) Haidt claims the rider can only nudge the elephant in any one direction, but the elephant is ultimately the one in charge of where we wind up.

I actually like Haidt's "press secretary" metaphor better. Our conscious mind is the analog of the press secretary for our true, complete self, which is largely nonconscious. Our conscious mind is obligated to speak out and put a 'spin' on our actions, in order to explain them not just to others, but to ourselves as well. There is a lot more going on outside our conscious awareness than we realize. If you're into this stuff, I highly recommend the recent book called The Opacity of Mind: An Integrated Theory of Self Knowledge by Peter Carruthers, discussed here.

As a result, I'm a bit skeptical that we can introspect and figure out our real motivations for anything, including practicing CR. It's something we do, and then rationalize to ourselves and others why. But polls like this one can be fun and informative nonetheless, for those willing to participate. On that note, I just checked SurveyMonkey, and we're up to 21 responses, including most of the long-timers and active folks on the forums. Thanks everyone! I'll report the results tomorrow. But we still haven't gotten responses from Saul or Michael, based on the demographics of people who've participated. Perhaps I'll ping them both directly.

--Dean

Sthira · September 3, 2016

The problem, of course, is that it's in retrospect not at all a CR study, but an obesity-and-junk-food-avoidance study, and therefore can only be presented at as evidence of the translatability of CR dishonestly, self-deludingly, ignorantly, or with extreme caution in specific findings.

I agree "fluke" is a peculiar word; but the (UW) study has only one interpretation, are you sa-saying? "Science" (as practiced here along the soft edges) is entangled with art, which refuses one interpretation, no?

And what does (the UW study) "...can only be presented at as evidence of the translatability of CR dishonestly, self-deludingly, ignorantly, or with extreme caution in specific findings..." mean? These are emotional words, and I ain't catching your drift yet. But I'd like to!

...I'm a bit skeptical that we can introspect and figure out our real motivations for anything, including practicing CR. It's something we do, and then rationalize to ourselves and others why.

Post jungle trip it may be interesting to revisit this (what is it, "conviction")?

The Observer · September 3, 2016

Thank you for your extremely thorough answer, Dean. I almost feel like I stole hours of your life away from you, and we all know how special time is for us futurists waiting for LEV. :)xyz

Then again, I've been browsing the forum and I get the feeling you probably don't mind discussing these things and even repeating yourself for the gazillionth time to a noob such as myself. I can sense your passion emanating through your words, not to mention your knowledge that is truly impressive.

But where does this leave me?

I've stumbled across CR every now and then during the last decade. Mouse studies, monkey studies, IGF-1, autophagy, sedentary vs active lifestyle, ~18 vs ~23 BMI... At first you find mostly positive arguments about all these things, but then when you look into them, they start falling off one by one. It seem to me each of these coins have two sides and the end total is close to null.

Even autophagy. I did put my last money on autophagy because it really sounds like a scientifically bullet proof method for at least a moderate amount of life extension. But now you (almost) took even autophagy away from me, by pointing out the possible negative side effects of autophagy. :huh:

And then there is my personal experience. Like I said I am quite different. As a child I rejected food and was always the smallest, always lagging behind. I probably hit puberty only at the age of ~18 and today, comparing my skin to other people and researching the web, I would say I must be more like 28-30 biologically, having no wrinkles whatsoever, not the actual 38. Well, perhaps I am 50 inside, who knows. :D I just don't know what to think of it all. Or looking at celebrities like Jared Leto, who I think also attributes his youthful appearance to his eating habits.

Anyway, for now I'm staying with my current plan, which is one 24-hour fast, 1-2 CR days and 4-5 normal eating days every week, which should allow me to settle at around 20-21 BMI.

Will add one slightly off topic question I've been obsessing about lately: When do you guys think humanity will conquer or bring under control major diseases like cancer, dementia and cardiovascular diseases? I've been following scientific progress in medicine and I personally believe this date to be around 2050, which should then help many of us, who are younger than ~65 today, live to be 100+ and drastically increase our chances of catching the Longevity Escape Velocity train. Do you think this date to be overly optimistic?

10x. May all of you live long and prosper.

Edit: P.S.: I completed the survey and selected for being a long time practitioner of mild-CR (21-30 years), even though I practiced it unknowingly and unwittingly.

Dean Pomerleau · September 3, 2016

Observer,

I almost feel like I stole hours of your life away from you, and we all know how special time is for us futurists waiting for LEV.

No worries Observer. I enjoy talking about this stuff (obviously), or I wouldn't do it!

When do you guys think humanity will conquer or bring under control major diseases like cancer, dementia and cardiovascular diseases?

If I had to speculate, I think 2050 is not a bad guess for getting major forms of dementia and CVD under control - those two are pretty circumscribed diseases. Cancer on the other hand is likely to be more of a challenge because it is so diverse, sneaky and likely to be exacerbated by other treatments that may be important for boosting longevity (e.g. stem cell therapy, telomerase expression).

But 35 years is a long time. I'd say there's a chance that substantial portions of the SENS strategy with bear fruit by then, despite the pessimism I've expressed recently.

--Dean

Michael R · September 3, 2016

All:

Michael,

You're developing habits of question-beggary and nitpickery which are not productive. ☺

I don't think there's any conceivable sense that I've engaged in question-beggary, and this is a large lyme-bearing tick, not a nit.

The only person that I know who thinks something at least close to "that the CR primate studies were a fluke" is Saul, and he has explicitly said that he's not in it for the life extension anyway.
I agree with Saul and with you - the disappointing results of the CR primate studies may not be a good reason to dismiss human CR outright (due to methodological flaws), but neither are they any sort of evidence in favor of continued optimism or motivation for personal practice. But that doesn't stop some people... Rodney would be another such long-timer who seemed to be in the "CR Optimism" camp, suggesting recently that:

...restriction of calories is more important than everything else combined by, perhaps, nearly an order of magnitude...

Nowhere in Rodney's post does he even mention the results of the primate studies as a basis for CR optimism, nor (to my quite specific point) did he rely on the contention that their outcomes were "flukes" in order to sustain such optimism.

But stepping back a moment from the particular words I chose to characterize the gist of the "CR Optimism" mindset

This is a bit of Lucy-pulls-the-football. The substance of those words are the very thing to which I'm objecting.

CR Optimism - Continued optimism that the rodent CR results will scale directly to humans (i.e. 20-40% extension of remaining lifespan = 10-20 human years), since rodents lose weight on CR and so do humans.

Get my drift?

once again Michael you've missed the forest for the trees. Regardless of people's perspective on the monkey study results, I stand by my observation that "CR Optimism" is one possible motivation for some long-time CR practitioners continuing to practice

Of course it is. Nowhere did I object to your suggesting that "'CR Optimism' is one possible motivation for some long-time CR practitioners continuing to practice:" indeed, it's my assumption that some degree of such is an important reason for nearly all such adherence, and have been surprised in cases where people have continued to practice without it (such as you, when you first stopped following the List, continuing CR entirely for the emotional tranquility it gives you, despite disengagement from life extension as a source of motivation). What I quite specifically objected to, very explicitly, is your suggestion that such optimism relies on the notion that the CR primate studies can be dismissed as "flukes." They cannot: the UWisc study — on its face, support for such optimism — has to largely be disregarded for other reasons, and the NIA study is a complex evidentiary puzzle with which we have to self-critically grapple and continue to incorporate along with the wider body of CR evidence — emergent. rediscovered, and re-interpreted.

Why the silence from you on your personal CR motivations?

I really can't imagine that this isn't clear to all concerned, and I certainly made them clear at the Conference in a quite public way on several occasions, including while standing at the front of the room leading the group discussion on future pathways for the Society with you. CR optimism (albeit of a more cautious sort than I had from say 2009 to 2012) it is my main reason by a very wide margin (with several of your other motivators actually being facets of that overriding one). But I am not so ignorant or self-deluded as to sustain that optimism by dismissing the NIA study as a "fluke."

I didn't bother taking the poll because I was instead busy taking you to task for grossly caricaturing the basis that people have for sustaining such optimism.

Better watch out. Next thing you know there'll be taco trucks on every corner. Sorry but I couldn't help pointing out a great example of rational priority setting in action...

Once Trump is defeated, maybe Bob will see his ways and work to get those streetside entrepreneurs to start offering low-Calorie, extra-veggie, Quorn grounds-packed lettuce-leaf-wrapped burritos.

The problem, of course, is that it's in retrospect not at all a CR study, but an obesity-and-junk-food-avoidance study, and therefore can only be presented at as evidence of the translatability of CR dishonestly, self-deludingly, ignorantly, or with extreme caution in specific findings.

I agree "fluke" is a peculiar word; but the (UW) study has only one interpretation, are you sa-saying? "Science" (as practiced here along the soft edges) is entangled with art, which refuses one interpretation, no?

I don't think there are any credible interpretations that don't include this basic one, no.

And what does (the UW study) "...can only be presented at as evidence of the translatability of CR dishonestly, self-deludingly, ignorantly, or with extreme caution in specific findings..." mean? These are emotional words, and I ain't catching your drift yet.

The only ways that a person could argue that the results of the UWisc study support the idea that the anti-aging effects of CR seen in rodents will also be observed analogously by humans practicing CR are (a) dishonestly, by consciously saying such when one knows that they don't; (b] self-deludingly, by half-consciously convincing oneself that they do when some part of you recognizes that they can't; (c] ignorantly, by not actually being informed about the details of the study; or with extreme caution in specific findings, by looking at a specific finding very carefully and in the context of a lot of other data, to come to some narrow balance-of-evidence conclusion on a defined question that would be ridiculous to reach on the primary basis of such or that would be problematic to assert without first explaining its compatibility with the UWisc result in question.

Dean Pomerleau · September 3, 2016

Wow Michael,

Once again you've got my head spinning, particularly with that response to Sthira at the end.

But first, regarding your objections to my earlier post. I still think you're engaging in nitpickery, but I think I understand your specific objection better now. I'll acknowledge that suggesting people may remain optimistic about CR longevity benefits as a result of viewing the CR primate study as a 'fluke' probably isn't accurate at least for rational folks. Instead they may (and in any case should) view the CR primate studies as weak and equivocal (but on the whole not positive, and perhaps even somewhat negative) evidence due to their methodological flaws, but may nevertheless still harbor optimism for human CR longevity benefits based on other evidence, e.g. the hope that the CR rodent data will translate to humans, or (heaven forbid) epidemiological evidence alleging to show a human CR longevity effect like the Okinawans. Whether they should rationally harbor such hope is debatable IMO...

To wit, you wrote:

CR optimism (albeit of a more cautious sort than I had from say 2009 to 2012) it is my main reason by a very wide margin (with several of your other motivators actually being facets of that overriding one). But I am not so ignorant or self-deluded as to sustain that optimism by dismissing the NIA study as a "fluke."

I didn't bother taking the poll because I was instead busy taking you to task for grossly caricaturing the basis that people have for sustaining such optimism.

Thanks for clarifying that and thanks especially for filling out the poll now that you've (presumably) finished chastising me ☺.

Despite not including your name, it's obvious to me from comments accompanying the survey that the most recent response was almost certainly from you Michael. I'm planning to post a summary of the results tomorrow, and I was planning to (anonymously) share some of the comments and motivations people wrote about in the comment box. But I realize that your response is pretty distinctive that it would be fairly obvious to anyone with a long history around here that you wrote it. I know how important privacy is to you, so please let me know whether I should or shouldn't include your (anonymized) comment about CR motivation in my summary.

Including responses directly from people reading this thread, and responses to my post about the survey on the CRS Facebook group, we're now up to 25 total responses - a new record for any of the surveys I've done! The results are really interesting, and I'll try to parse and share them with everyone tomorrow. If you haven't yet filled it out there is still time - so please do!

(Saul, I'm looking at you, although there is one recent anonymous response that might fit your profile...).

--Dean

Sthira · September 4, 2016

The only ways that a person could argue that the results of the UWisc study support the idea that the anti-aging effects of CR seen in rodents will also be observed analogously by humans practicing CR are (a) dishonestly, by consciously saying such when one knows that they don't;

Check. No one being dishonest, presumably.

(b] self-deludingly, by half-consciously convincing oneself that they do when some part of you recognizes that they can't;

In the face of inconclusive evidence, we dream CR because it's the best option we have so far?

(c] ignorantly, by not actually being informed about the details of the study;

Check. Anyone here not informed about the details?

or with extreme caution in specific findings,

To which specific findings should we exercise extreme caution?

by looking at a specific finding very carefully and in the context of a lot of other data, to come to some narrow balance-of-evidence conclusion on a defined question that would be ridiculous to reach on the primary basis of such or that would be problematic to assert without first explaining its compatibility with the UWisc result in question.

What specific finding are you looking at very carefully? Is context CR extends LS in many other species that aren't primates?

Dean Pomerleau · September 4, 2016

Sthira,

Michael wrote:

...with extreme caution in specific findings, by looking at a specific finding very carefully and in the context of a lot of other data, to come to some narrow balance-of-evidence conclusion on a defined question that would be ridiculous to reach on the primary basis of such or that would be problematic to assert without first explaining its compatibility with the UWisc result in question.

What specific finding are you looking at very carefully? Is context CR extends LS in many other species that aren't primates?

I confess I'm about as baffled as your are by Michael's word salad on that one. And while I'm extremely hesitant to put words in Michael's mouth (n^th bitten, n^th+1 shy...), I'll go ahead and live dangerously by taking a crack at it.

Michael might mean something like the following (which I'm making up): "the balance of evidence from rodents and other species suggest that CR extends lifespan if and only if accompanied by X (where X might be 'low IGF-1' or 'hunger' for example). Since the CR monkeys didn't show X, it's not surprising they didn't enjoy lifespan benefits from CR. At least some human CR folks exhibit X, so CR might still work in people, despite the disappointing, or at best ambiguous monkey CR results."

Let's see if Michael gets angry enough at my caricature this time to continue engaging with us if for no other reason than to castigate me again... ☺

--Dean

Michael R · September 4, 2016

All:

Despite not including your name, it's obvious to me from comments accompanying the survey that the most recent response was almost certainly from you Michael. I'm planning to post... some of the comments and motivations people wrote about in the comment box. But ... it would be fairly obvious to anyone with a long history around here that you wrote it. I know how important privacy is to you, so please let me know whether I should or shouldn't include your (anonymized) comment about CR motivation in my summary.

Thank you very much for being respectful on this. But yes: please feel free to quote (and, for clarity, attribute) my comments.

If you haven't yet filled it out there is still time - so please do!

(Saul, I'm looking at you

That's a pretty neat trick from across the state border ... No sign of macular degeneration yet, I take it ;) .

(Seriously: sorry to drift off-topic, and feel free to start a new thread, but speaking of which: have you seen the two prospective cohort studies finding that olive oil consumption is linked to a rather dramatically lower risk of macular degeneration?).

The only ways that a person could argue that the results of the UWisc study support the idea that the anti-aging effects of CR seen in rodents will also be observed analogously by humans practicing CR are (a) dishonestly, by consciously saying such when one knows that they don't;
Check. No one being dishonest, presumably.

Alas, some people sure seem to be. At least, it seems more plausible than that the specific individuals in question are ignorant or self-delusional.

(b] self-deludingly, by half-consciously convincing oneself that they do when some part of you recognizes that they can't;
In the face of inconclusive evidence, we dream CR because it's the best option we have so far?

Well, of course — but that needn't rise to the point of self-delusion, even if it tends to color your view. "In the face of inconclusive evidence," I for one lean toward thinking that CR will translate, and certainly the reason I take the risk of engaging in a radical lifelong self-experiment with an unproven, difficult, and risky intervention is "because it's the best option we have so far" — but I don't delude myself into thinking that the UWisc study is good evidence supporting such.

(c] ignorantly, by not actually being informed about the details of the study;
Check. Anyone here not informed about the details?

Goodness gracious: lots of people, some of whom really ought to know better.

or with extreme caution in specific findings,
To which specific findings should we exercise extreme caution?

ALL OF THEM! Read teh whole sentence, and remember what you originally asked, silly ;) . You can't take any of the UWisc findings at face value, because (again) the UWisc study is not really a CR study.

Michael wrote:
...with extreme caution in specific findings, by looking at a specific finding very carefully and in the context of a lot of other data, to come to some narrow balance-of-evidence conclusion on a defined question that would be ridiculous to reach on the primary basis of such or that would be problematic to assert without first explaining its compatibility with the UWisc result in question.

I confess I'm about as baffled as [sthira] by Michael's word salad ...

Michael might mean something like the following (which I'm making up): "the balance of evidence from rodents and other species suggest that CR extends lifespan if and only if accompanied by X (where X might be 'low IGF-1' or 'hunger' for example). Since the CR monkeys didn't show X, it's not surprising they didn't enjoy lifespan benefits from CR. At least some human CR folks exhibit X, so CR might still work in people, despite the disappointing, or at best ambiguous monkey CR results."

In context, I couldn't possibly have meant that, since I was talking about interpreting the results of the UWisc study, and the UWisc primates did (read naïvely) enjoy life extension. Tautolgically, there's no need to decide why life was not (as your made-up interpretation posits) extended in UWisc when it was. But of course — again! — the UWisc study wasn't a CR study, but a junk-food-and-obesity-avoidance study. The life of the "CR" animals wasn't extended: it just wasn't shortened by diet-induced metabolic mayhem.

OTOH, there is obviously a need to explain the non-extension in the NIA study. One such explanation is, of course, that CR doesn't translate to primates. And for the NIA study, it's definitely worthwhile exploring exactly the kind of analysis that you've just suggested (as, of course, I did in some sections of my SENS Research Foundation blog post on the monkey CR studies.

Dean Pomerleau · September 4, 2016

Thanks for the clarification Michael, and the permission to post and attribute your survey comment. I'm afraid my report on the survey will be delayed a day. I got a bit distracted by cows today ☺.

(Seriously: sorry to drift off-topic, and feel free to start a new thread, but speaking of which: have you seen the two prospective cohort studies finding that olive oil consumption is linked to a rather dramatically lower risk of macular degeneration?).

Drift away!

Seriously, thanks for the studies, and for remembering that risk of macular degeneration is apparently one of my achilles heels based on 23andMe data and to some extent, on OCT scans I've had showing a relatively thin macula for someone my age. I'll definitely read the papers. Fortuitously, I've got my yearly opthamologist appointment in a couple weeks during which I'll get another OCT scan. I'll definitely take a look at those two studies ahead of my appointment so I can ask my doctor about them, and start a new thread if appropriate based on them and/or my scan results.

Finally, thanks once again for clarifying what you were saying about the CR primate study(ies). I'd be interested to hear your insights about cow CR as well, seeing as they were also part of your mega blog post about CR in primates.

--Dean

The Observer · September 5, 2016

Just found this short video presentation https://www.youtube.com/watch?v=h7fs33Jewsg of Michael from 2010 (I apologize if I just violated his privacy by posting this, in which case feel free to remove the link or delete the whole post) and in it he emphasizes how every calorie is toxic and the fewer calories you consume, the longer your lifespan is extended.

Oh, how I wish this would be a scientific fact of life. I would go berserk practicing CR. I truly would, especially since it implies (or at least that's how I took it) some substantial gains in terms of additional years of life. But I reckon we cannot really confirm that today. Wonder if Michael still stands by this words today and if so, what is he basing them on. After all, the publication of the NIA monkey study results came out in 2012? and therefore after his presentation I linked. If someone can point me to the right direction, perhaps a link?

Anyways. It seems to me you guys, Dean and Michael, are/were somewhat on the opposite sides of the spectrum, when it comes to CR optimism. That is, unless he too evolved his opinion over the years. You two must have had some epic battles over the years. I glanced over some of them, but that's about it. Must go search through the forum archives right away. :P

Dean Pomerleau · September 5, 2016

Observer,

Just found this short video presentation https://www.youtube....h?v=h7fs33Jewsgof Michael from 2010 (I apologize if I just violated his privacy by posting this, in which case feel free to remove the link or delete the whole post)

Not at all Observer! Anything on YouTube is fair game as far as I'm concerned, especially when it was a public talk like that one.

In fact, I've edited your post to embed the video at the bottom so everyone can watch it more easily. Of course you won't be surprised to learn that we've talked about that video before, and the optimism Michael expresses that CR will be able to get us over the hump until real treatments to stop and reverse aging (presumably based on SENS) become available. That was quite a sales job. I liked the part about CR enabling us to "spend a lot more time on the golf course and tennis courts in the meantime" (4:30). ☺

Of course Michael's talk was in 2008, several years before the disappointing results of the CR primate studies were known. To his credit, Michael has since tempered his advocacy of the "Calories, Calories, Calories" mantra which he so boldly and eloquently expressed starting at 5:15 in that video (my emphasis):

It is a simple mathematical relationship. Calories, Calories, Calories. Another way to put this is that every calorie you put in your system is toxic. The fewer calories you consume, the longer your lifespan is extended until you get to the very, very, very, very [yes, that was four very's. I counted - DP] edge of starvation when you're not dying of aging, your dying because you can't carry out the basic cellular functions of life.

Funny, no mention whatsoever of exercise...

Moreover, I've always thought I was making it up and therefore being a bit unfair when I've chided Michael and others on a couple occasions (e.g. here, here, here, here, here, here, here, here, here, here, here and here) for (formerly?) subscribing to the "Calories, Calories, Calories" mantra. I thought I was simply drawing a humorous parallel with the "Location, Location, Location" mantra in real estate. I never knew (or remembered) that Michael actually said it, and said it boldly and confidently in a widely-viewed public forum, no less. Glad to clear that up. I feel better now. ☺

Wonder if Michael still stands by [these] words today and if so, what is he basing them on. After all, the publication of the NIA monkey study results came out in 2012? and therefore after his presentation I linked. If someone can point me to the right direction, perhaps a link?

Michael has responded to at least a couple of my recent chides linked to in those here's above, clarifying his current perspective. It seems he has indeed curbed and qualified some of his CR enthusiasm since that time, although as he expressed above (and I'll discuss more later today I hope...), Michael remains perhaps the most optimistic of any well-informed, long-term CR practitioners or researcher I know regarding the likelihood and magnitude of CR's effects translating to humans. I certainly could be wrong, but it seems to me his attitude may be based more on psychology and public perception than confidence in the underlying scientific evidence at this point.

It seems to me you guys, Dean and Michael, are/were somewhat on the opposite sides of the spectrum, when it comes to CR optimism.

Ya think!? ☺ Seriously, Michael and I have a good time. At least I do... I consider him a friend, and that goes for Saul as well, who I tussle with almost as much as Michael, and often more harshly to boot! ☺ From my point of view, it's all intended to be good fun and to attract eyeballs.

You two must have had some epic battles over the years.

Sadly (for me), our battles of late have been rather one-sided. In fact, sometimes it seems I'm tilting at windmills.

I like to think it's because either Michael agrees with me or can't counter my arguments, but I suspect (and hope) it's because he's just too damn busy actually doing something at SENS to defeat the scourge of aging to bother engaging with the likes of me...

But let me try once more to raise Michael from his dogmatic slumber...

Dean wrote previously (putting hypothetical words in Michael's mouth):

"the balance of evidence from rodents and other species suggest that CR extends lifespan if and only if accompanied by X (where X might be 'low IGF-1' or 'hunger' for example). Since the [NIA] CR monkeys didn't show X, it's not surprising they didn't enjoy lifespan benefits from CR. At least some human CR folks exhibit X, so CR might still work in people, despite the disappointing, or at best ambiguous [NIA] monkey CR results."

to which Michael responded:

OTOH, there is obviously a need to explain the non-extension in the NIA [CR primate] study. One such explanation is, of course, that CR doesn't translate to primates. And for the NIA study, it's definitely worthwhile exploring exactly the kind of analysis that you've [Dean] just suggested (as, of course, I did in some sections of my SENS Research Foundation blog post on the monkey CR studies.

Michael, I know you realize this, but for the newcomers among us.

The two X's I suggested for filling in the blank (i.e. "low IGF-1" and "hunger") in order to keep alive the hope that CR will work in humans despite apparently not benefitting the monkeys in the NIA CR study, were complete straw men.

Ironically, it was you, Mr. CR Optimism, who burst my bubble about the hope of no change in IGF-1 in the CR monkeys. IGF-1 apparently did go down in the NIA CR monkeys, as it does in rodents and CRed people, but that didn't help the NIA monkeys to live any longer than controls. So it appears we can scratch IGF-1 off the list of hopeful differences between the NIA monkeys and human CR folks.

Regarding hunger, Michael, I think you and I both know by now how paper-thin is the evidence supporting the so-called "hunger hypothesis" (HH - namely that for CR to work you've got to not only restrict calories, but experience hunger while doing it). For those of you who aren't familiar with the HH or the evidence surrounding it, start here. Be prepared to be disheartened if you're a HH fan, or heartened if you are like me and enjoy that feeling of fullness after a big, high-fiber, meal.

Be sure not to miss this key post debunking some vague ideas some people have about the HH. But most of all, if you like passive-aggressive arguments (which it sounds like you do Observer) you won't want to miss this point (from Michael) and counterpoint (by me) on Michael's key argument to support the HH based on evidence about the so-called hunger hormone NPY. I'll leave it as an exercise for the reader to judge who won that particular skirmish...

So what is my last remaining hope for the "X Factor" that was missing from the NIA primates that could explain the failure of CR to extend their lifespan and keep alive the hope for human CR benefits?

It is, you guessed it, cold exposure. As discussed here, unlike the rodent studies where CR usually works at least if the mice are kept at a chilly (for them) temperature, the NIA monkeys were housed at an average daily temperature that was slightly higher than thermoneutrality. If, as I hypothesize and the evidence strongly suggests, it is CR + CE synergy that might (modestly) extend lifespan in warm-blooded mammals, it should come as no surprise that the warm-housed CR monkeys in the NIA study didn't live any longer than controls.

P.S. Responses to the CR Motivation Survey keep rolling in. Four new ones came in overnight - including Saul's. Thanks Saul! So I'm going to keep the poll open for at least one more day before summarizing. Stay tuned, and fill out the survey if you haven't yet!

--Dean

Michael R · September 5, 2016

All:

Wonder if Michael still stands by [these] words ["Calories, Calories, Calories," etc] today and if so, what is he basing them on. After all, the publication of the NIA monkey study results came out in 2012? and therefore after his presentation I linked. If someone can point me to the right direction, perhaps a link?

It sounds like you're confusing two different questions. One is the role of different putative factors independent of energy intake per se in the mechanisms of CR (which, as I recently clarified, continue not to fly :

"Calories, Calories, Calories" is about the mechanism of CR: it's about Calorie intake, and not (as people have often postulated) specific sources of energy (protein, carbs, and fat have all been fingered by different people), nor negative energy balance (exercise, UCP-2, etc's uniform failure to extend max LS demonstrates this), or (except to a minimal degree) reduction in adiposity.

The big problem with extra Calories in, of course, is that it normally leads to obesity [sNIP]

The other is the translatability of CR, for which the primate data are obviously important, albeit unfortunately inconclusive and a bit of a shambles.

As to what "CCC" is based on: well, a lot of things, really, but amongst them are the failure of reasonable-seeming alternative explanations (like the above) to pan out when tested, and the actual mathematical relationship between energy intake and lifespan extension across studies:

Michael remains perhaps the most optimistic of any well-informed, long-term CR practitioners or researcher I know regarding the likelihood and magnitude of CR's effects translating to humans. I certainly could be wrong,

You are ;) .

but it seems to me his attitude may be based more on psychology and public perception than confidence in the underlying scientific evidence at this point.

No, it's based primarily on the science, but reinforced by a lot of other things (as you know, as Holder of the Survey Data). One's confidence needn't be overweening to be adequate, particularly when reinforced by other factors.

the balance of evidence from rodents and other species suggest that CR extends lifespan if and only if accompanied by X (where X might be 'low IGF-1' or 'hunger' for example). Since the [NIA] CR monkeys didn't show X, it's not surprising they didn't enjoy lifespan benefits from CR. At least some human CR folks exhibit X, so CR might still work in people, despite the disappointing, or at best ambiguous [NIA] monkey CR results."

there is obviously a need to explain the non-extension in the NIA [CR primate] study. One such explanation is, of course, that CR doesn't translate to primates. And for the NIA study, it's definitely worthwhile exploring exactly the kind of analysis that you've [Dean] just suggested (as, of course, I did in some sections of my SENS Research Foundation blog post on the monkey CR studies.

Michael, I know you realize this, but for the newcomers among us.

The two X's I suggested for filling in the blank (i.e. "low IGF-1" and "hunger") in order to keep alive the hope that CR will work in humans despite apparently not benefitting the monkeys in the NIA CR study, were complete straw men.

You have, of course, been in the habit of making straw men of my arguments and positions of late, and also misunderstanding my clear statements and taking them out of context so often that I have to begin to wonder if it's intentional.

Ironically, it was you, Mr. CR Optimism, who burst my bubble about the hope of no change in IGF-1 in the CR monkeys.

Right. So why put it into my mouth as an example of the kind of argument I would make? Yes, your ventriloquist-doll Michael is making a reasonable KIND of argument, but the specific example is, as you say, contrary to the data, and you know that I've pointed this out myself. So why do that? And why do it and then come back in a subsequent post and act as if I'd actually said it and you need to patiently explain it to newcomers?

Regarding hunger, Michael, I think you and I both know by now how paper-thin is the evidence supporting the so-called "hunger hypothesis" (HH - namely that for CR to work you've got to not only restrict calories, but experience hunger while doing it). For those of you who aren't familiar with the HH or the evidence surrounding it, start here. Be prepared to be disheartened if you're a HH fan, or heartened if you are like me and enjoy that feeling of fullness after a big, high-fiber, meal.

Be sure not to miss this key post debunking some vague ideas some people have about the HH. But most of all, if you like passive-aggressive arguments (which it sounds like you do Observer) you won't want to miss this point (from Michael) and counterpoint (by me) on Michael's key argument to support the HH based on evidence about the so-called hunger hormone NPY. I'll leave it as an exercise for the reader to judge who won that particular skirmish...

HH, OTOH, is still a quite viable hypothesis to note. Part of what you seem to genuinely not be distinguishing here and in your linked critiques is that there is a difference between signaling via NPY and similar mediators (which the HH hypothesizes to be involved in the mediating role of such factors between reduced energy intake and slowed aging or particular aspects of the CR effect), subjectively experienced hunger (to the extent that that is a sound construct in most non-human animals), and eating behavior and weight gain induced (or not) by that signaling in the presence of food. And yes, in this case, I do plead guilty to leaving behind something that actually is cryptic ;) .

But you seem to still be not paying attention to the overriding thing about the NIA non-result, which I pointed out again in this very thread:

as discussed in extensive detail, and given even more striking weight by additional information revealed by Richard Miller at the last CR conference, the failure of the NIA study to demonstrate extended lifespan was ... inconclusive, first and foremost because of the combination of having been statistically underpowered from the outset to report a life extension outcome (that not having been its original intent) and the animals having been never much more than 20% CRed and not much more than 10% for most of the study — plus many other details, as discussed.

Reference
Speakman JR, Mitchell SE, Mazidi M. Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone. Exp Gerontol. 2016 Mar 19. pii: S0531-5565(16)30069-9. doi: 10.1016/j.exger.2016.03.011. [Epub ahead of print] Review. PubMed PMID: 27006163.

Gordo · September 5, 2016

One thing that I still don't understand is the belief by some that CR is the only thing "proven" to extend lifespans or healthspans. When you start digging in and doing research, first you find that the evidence for CR in and of itself is not impressive, even in mice, let alone primates. But you do find evidence for many things that should increase lifespans and healthspans in humans: time restricted feeding, cold exposure, exercise, diverse plant based diets (and their related amino acid profile - i.e. lower than typical methionine, more generally lower than average protein intake and lower IGF-1), reducing advanced glycation end products (including avoiding high blood sugar), etc. It seems like most of the folks here already do "most of the above" and that is one reason why I read & participate here. I doubt that in primates any given single factor from this list would be all that impressive in and of itself, but a combination of all of the above plus a reasonable BMI (based on the exhaustive meta analysis that have been published) is probably the best humans can do right now as we await technological solutions that can remove accumulated damage and regenerate healthy cells & tissue.

If you want a longer life, you should be thinking about the top causes of death. In particular the first focus should be on avoiding atherosclerosis, which is best accomplished by content of diet in my opinion, eat plant foods noted in research to lower LDL, and get your heart pumping vigorously at least once a day, and you won't die from heart disease or stroke. Eat plants noted for their anti-cancer and anti-inflammatory properties, and you are less likely to die from cancer or develop arthritis (avoid foods noted for their links to cancer). Achieve superb blood sugar control through diet, time restricted feeding, exercise, and cold exposure (personally I think cold exposure is the 'easy' way) and you will avoid diabetes and possibly Alzheimer's as well as avoiding the damage caused by advanced glycation end products (which likely plays a role in heart disease, in particular causing endothelial damage which starts the process of plaque formation). Get enough sleep, especially rejuvenating, profound, deep sleep, and let your body repair itself daily (again in my opinion the best way to do that is via cold exposure - although as far as I know there haven't been studies on this yet). In my opinion, the only value for CR in and of itself is to achieve/maintain an ideal BMI for your age and build.

-Gordo

Sthira · September 5, 2016

...evidence for many things that should increase lifespans and healthspans in humans: time restricted feeding, cold exposure, exercise, diverse plant based diets (and their related amino acid profile - i.e. lower than typical methionine, more generally lower than average protein intake and lower IGF-1), reducing advanced glycation end products (including avoiding high blood sugar), etc.

Anything else to add here? Hit RDAs, maybe water-only fasts every now and then, experiment with wildcard placebo stuff (maybe resveratrol, pterostilbene/NR, metformin... recognizing of course there's probably no there there in any of it) sunscreen, seatbelts, smile and cheer the hell up, all ye disappointed tribemates... One thing I need to watch in my own behavior is trying to do too much (unproven shiz...) due to frustration, impatience, OCD...

It seems like most of the folks here already do "most of the above" and that is one reason why I read & participate here. I doubt that in primates any given single factor from this list would be all that impressive in and of itself, but a combination of all of the above plus a reasonable BMI (based on the exhaustive meta analysis that have been published) is probably the best humans can do right now as we await technological solutions that can remove accumulated damage and regenerate healthy cells & tissue.

If you want a longer life, you should be thinking about the top causes of death. In particular the first focus should be on avoiding atherosclerosis, which is best accomplished by content of diet in my opinion, eat plant foods noted in research to lower LDL, and get your heart pumping vigorously at least once a day, and you won't die from heart disease or stroke. Eat plants noted for their anti-cancer and anti-inflammatory properties, and you are less likely to die from cancer or develop arthritis (avoid foods noted for their links to cancer). Achieve superb blood sugar control through diet, time restricted feeding, exercise, and cold exposure (personally I think cold exposure is the 'easy' way) and you will avoid diabetes and possibly Alzheimer's as well as avoiding the damage caused by advanced glycation end products (which likely plays a role in heart disease, in particular causing endothelial damage which starts the process of plaque formation). Get enough sleep, especially rejuvenating, profound, deep sleep, and let your body repair itself daily (again in my opinion the best way to do that is via cold exposure - although as far as I know there haven't been studies on this yet). In my opinion, the only value for CR in and of itself is to achieve/maintain an ideal BMI for your age and build.

This is all great advice, but unfortunately as you know the real solutions are out of our lay hands. I suspect researchers with lab access are trying compounds and approaches secretly on themselves (think Fahy and the thymus) and they just can't or won't tell anyone. And with billions being pumped into Calico, much more is happening there than just pharma-centered study. But who's saying anything edgy and with freedom just because of the shitty litigiousness of this stupid culture, the FDA.. blah...

Aging celebrities with money and connections are people to watch, and we are watching, of course. Their careers are often based on their youthful appearances.

Dean Pomerleau · September 5, 2016

Michael,

Right. So why put it [i.e. the possibility that CR failed in NIA monkeys because their IGF-1 didn't drop, which (unfortunately) it did - DP] into my mouth as an example of the kind of argument I would make? Yes, your ventriloquist-doll Michael is making a reasonable KIND of argument, but the specific example is, as you say, contrary to the data, and you know that I've pointed this out myself. So why do that? And why do it and then come back in a subsequent post and act as if I'd actually said it and you need to patiently explain it to newcomers?

Sorry I pretended it was coming from you, but I was quite sincere in my concern that newcomers would get the impression from my ventriloquist act that both of us thought IGF-1 was still on the table as an explanation for why CR might have failed to extend lifespan in the NIA monkeys but still succeed in humans. Since in your response you didn't dispel IGF-1 (or the hunger hypothesis) as credible explanations for the NIA CR monkey disappointment, I followed up to clarify, and to see just how much stock (or doubt) you are putting in both these explanations these days. The fact that you've previously dismissed the IGF-1 hypothesis in a post buried on another thread, would be little help to newcomers. Even I had a bit of trouble tracking it down, and I recalled the precise context.

Similarly for your stance on the HH, which I thank you for clarifying (somewhat) in your latest post. I see the distinction you point to between NPY signalling, the feeling of hunger, and eating behavior / weight gain resulting from the feeling of hunger. Further, I can understand in theory how the decoupling of these three distinct phenomena might influence the CR effect. Extrapolating (perhaps dangerously) from your (self-acknowledged) cryptic words, it's conceivable that it is NPY signalling, independent of hunger, which mediates the lifespan benefits of CR, at least in part. But if so, these questions remain:

Why call it the 'Hunger Hypothesis' if hunger is irrelevant and it's NPY that's doing the heavy lifting?
What evidence is there that NPY signalling (whether independent of hunger or not) mediates longevity? Don't give me your PMID 24682105 again, which is so full of holes that it's beyond conceivability to me that you could still think it relevant. The skin cancer study? P-u-l-lease. Speculations about possible NPY-mediated mechanisms? Get serious. Until I see a credible study showing either lifespan extension by upregulation of NPY[-signalling] or CR benefits being wiped out by NPY-knockdown (not -knockout) in otherwise normal, not genetically f*cked up rodents, it seems to me that suggesting NPY is involved in longevity is nothing more than idle speculation / wishful thinking.
Where is the evidence that NPY was actually not altered in the NIA CR monkeys? Food disappearance studies? Food motivation studies? Blood pressure!? Come on... You've got to do better than that, especially if you are proposing a break in the linkages between NPY, subjective hunger and eating behavior. Otherwise it's again just pure speculation.

But perhaps I've got it backwards, and you are (cryptically) suggesting the opposite, namely that it is hunger independent of NPY that mediates the CR longevity effect. In that case, I'm even more baffled by a) the lack of apparent evidence for this version of the HH, b) the lack of a putative NPY-independent, hunger-mediated, longevity-promoting mechanism, and c) your decision to change horses midstream from NPY to 'pure hunger' (or something else hunger-related?) that promotes longevity.

Finally, a point of agreement between us. I completely concur that by the end of the study the NIA monkeys were on pretty mild calorie restriction. Unfortunately, that fact, coupled with its other shortcomings, makes the disappointing results of the NIA monkey study less than the final verdict on the prospects for human CR.

But it does strongly suggest that if CR is going to have a chance of working better in people than a healthy, obesity-avoiding diet (like the NIA control monkeys ate), it will require quite serious, lifelong CR, which IMO becomes quite risky, especially as one enters one's senior years...

--Dean

Pea · September 6, 2016

Conflicting results in these types of low volume studies are common place. I'm way behind you guys, but it seems like we don't have enough numbers to determine life span conclusively, one way or the other.

On the other hand, the results of these studies do seem to suggest the monkeys who ate less were healthier and suffered less from age related disease, regardless of how long they lived.

Satan gathered his advisors and asked them how to destroy the meaning in people's lives. One said, "Tell them there is no god". Another, "Tell them their actions have no consequences." A third, "Tell them they can't improve their situation." Satan responded, "No, Those things won't matter to them. All we need to do is tell them .... There is plenty of time."

-Pea

Dean Pomerleau · September 7, 2016

CR Motivation Survey Results

First off, thanks to everyone for filling out the CR Motivation Survey. Between responses from people who read this thread, and those who saw my post about the survey on the CRS facebook group, we got 30 total responses. I had to eliminate one response because they left too many fields blank, giving us 29 total responses. Here are a few demographic facts about the respondents overall:

Gender: 25 men, 4 women - sadly, pretty typical of our group

Mean Age: 49 years

Mean BMI: 21.3

Mean CR Duration: 11 years

Looking over the data, there was a good split between people who've been practicing a relatively short time (which I defined for purposes of this analysis as < 8 years) and the long-timers, which I defined as 8+ years practicing CR. Given this definition, there was about an even split - 14 short- and 15 long-timers, giving us a good sampling of each. In the remainder of the discussion I'll analyze the data from the two groups in parallel. The so-called short-timers are represented by green (i.e. 'greenhorns' ☺) , and the long-timers by red in the discussions below. First, the demographics, broken down by short vs. long-timers:

These differences all look like we might expect - a higher ratio of men, lower BMI, greater age and longer time practicing CR in the long-timers. As you can see, the later three differences between groups are quite dramatic. Almost half (6/14) of the short-term folks have been practicing CR for under 1 year, and the vast majority (11/14) have been practicing 3 years or less. In short, we are truly looking at relative newcomers vs. seasoned veterans of CR.

Here is the real data everyone cares about - the weight folks in the two groups gave to the 10 different motivations for practicing CR. For people who don't remember what the different motivations represent, I've included the definitions at the bottom of this post:

These results are fascinating. I'll try to highlight some of the important overall results and difference between the short-term group (ST) and long-timers (ST) .

By far the two most popular reasons for practicing CR among both ST and LT groups were health-related, not longevity-related:

#1 was healthspan extension, described as "even if CR doesn't add extra years, it will keep us healthier during the years we've got.".

#2 was physical benefits, described as "We like the way CR makes us feel here and now, including things like increased energy, stamina, heat tolerance etc., regardless of what it does for our long-term health and longevity."

The #3 most important motivation was another health & well-being oriented reason - psychological benefits, described as "we appreciated the 'calm abiding' demeanor and outlook on life that long-term, serious CR seems to evoke, perhaps as a result of reduced testosterone." I assume people (especially mild, short-term CR folks) broadly interpreted this one to include all the good feelings CR gives them in terms of self-esteem, a sense of personal mastery, etc.

Next up (#4) among both groups was the first longevity-related item - Longevity Amplification which people will recall is the idea that CR give us a couple extra years, and life extension advances over the next few decades might turn a small (e.g. 2 year) life extension into something much larger. It seems both ST and LT folks put quite a bit of stock in Aubrey's idea of "Longevity Escape Velocity" (LEV).

Next up is the place where the two group first diverge. #5 for the ST folks was Appearance Benefits, described as "Some people are happier with the way they look practicing CR. Obviously this one will depend on the severity of one's CR practice, and the weight one starts at." It is probably no surprise that this is a higher priority (reaching the "moderately important" threshold on average) for ST folks than LT folks, since a) the ST folks are a lot younger, and presumably more interested in they way they look and b) the LT folks are a whole lot skinnier than the ST folks, and generally have a physique that is scrawnier than would be considered ideal, particularly for men in our culture.

For the LT folks, #5 seems a bit sad. It was Habit / Momentum, described as Many of us are creatures of habit, and habits are hard to break. Momentum keeps us going with our practice of CR, even when we have a sneaking suspicion that it may not be serving us (any longer). Acknowledging that we see ourselves as locked into a behavior that is probably no longer serving us seems rather unflattering, and a bit surprising since I generally consider us to be a pretty rational and self-reflective bunch. But apparently we're at least reflective enough (when probed) to recognize we sometimes run on autopilot and it may not be the wisest thing to do...

Nearly tying for #5 in the LT folks was my personal favorite Uniqueness / Exploration, described as "We enjoy being different, or believe there is genuine value in exploring new possibilities, and pushing the envelope of human potential." I realize now that I should have included "contributing to the scientific understanding of human aging and CR." as part of the description for this one. If I had, I suspect it would have pushed this one higher than Habit / Momentum, since I think the scientific contribution we think we might be making (e.g. via participating in Luigi Fontana's published studies of human CR) are an important motivation. At least it is for me.

Finally, coming in at #7 among LT folks, and #8 in ST folks was CR Longevity Optimism, described as Continued optimism that the CR primate studies were a fluke <sic>, and that the rodent CR results will scale directly to humans (i.e. 20-40% extension of remaining lifespan = 10-20 human years). After the discussion earlier in this thread with Michael, I realize the "fluke" part was likely an unfair and unfortunate characterization of the primate study, since it may have discouraged people from rating this one more highly. Nevertheless, I actually didn't expect this one to come in quite so low, especially among the LT folks, since it (presumably) is the motivation that got most of us started on this whole CR adventure in the first place.

For grins, and given Michael's permission, I decided to plot my responses (blue), his responses (orange) and the average of the long-timer responses (red again) in the graph below:

It will probably come as no surprise that Michael maxed out on the CR Longevity Optimism motivation giving it a "very important" rating, while I considered it not important at all. Clearly consensus means nothing on a subjective survey like this, but I found it interesting that there were only two people out of the 30 that took the survey who rated CR Longevity Optimism a 4 (Very Important) - Michael and Saul. In fact, 26 out of 30 rated CR Longevity Optimism to be "Moderately Important" or lower, and over half (18) said it was either of "no importance" or "minorly important" in their motivation for practicing CR.

Interesting to me, Michael rated as "moderately important" both Habit / Momentum and Sunk Costs (the latter defined as "We figure we've been practicing CR for so long that whatever damage (if there is any damage) to our physical body and to our social relationships has already been done, and so we might as well stick it out at this point, in hopes it will pay off").

He amplified some of his perspective on this in his candid and heartfelt comment in the text box at the bottom of the survey. Again with his permission, Michael wrote:

I was going to put "Self and Others' Perception," until I read the explainer in the Forum post. I don't continue to practice for those reasons, but I do take into account that if I — as a very prominent and long-term CR practitioner — were to quit, it would likely cause others who are now practicing CR to waver, or others who are just on the verge of giving it a shot to not take up the practice, in which case I might well have their aging and premature death on my hands. I also continue to practice in hopes of contributing to human CR science, potentially helping to more firmly establish or rebut translatability and informing the development of longevity therapeutics.

I'm in complete agreement with Michael on that last part "I also continue to practice in hopes of contributing to human CR science, potentially helping to more firmly establish or rebut translatability and informing the development of longevity therapeutics." I admire his dedication to the science, and personally consider contributing to understanding human aging and longevity science one of my own main motivations for continuing to practice the eclectic, CR-ish diet and lifestyle that I do.

But I found the first part of his comment both noble and a bit troubling at the same time. Michael, I totally understand how and why you feel a greater sense of responsibility for carrying the "CR torch" than the rest of us. At this point, given the MIA status of our President..., you are the person most prominently associated with the human practice of serious CR for it's potential longevity benefits. I actually feel a bit badly for you in this regard. From your CR Longevity Optimism rating, you clearly are still a "true believer" in the efficacy of CR, but I worry you might someday feel yourself caught an predicament analogous to that of the priests and ministers that Dan Dennett is trying to help with his Clergy Project, and whom he discusses in his paper titled Preachers Who Are Not Believers and in the book he co-authored called Caught in the Pulpit: Leaving Belief Behind. The stories of these clergymen and women are heartbreaking, as Dan discusses in this video, saying:

They are actually quite wonderful people, but they are caught in a terrible trap, because they wanted to do good, they wanted to help other people, and they thought this [becoming a clergyperson - DP] was the right way to do it. They piled diplomacy on diplomacy [in maintaining a facade with their parishioners - DP] until it became hypocrisy and there's no bright line between the two. They found that they were devoting their life to doctrines they no longer believed in order to carry on their good works. They had people that were deeply dependent on them and that they had made lots of promises to. So they were really caught in a set of circumstances that they had created not to get rich, but to help their fellow human beings. It's a very painful and very lonely place to be.

Make no mistake - I'm not equating belief that CR will (or may) provide a dramatic longevity benefit with belief in a bearded man in a white robe judging us from a throne somewhere beyond the clouds. I'm just saying that sometimes people lose their conviction in a formerly held sincere belief but find it hard to come out the closet about it for fear of the impact such an admission might have on other people who look up to them. In fact, in some ways your (hypothetical) dilemma is trickier and more heart-wrenching than preachers who've lost their faith. In the preacher case, since they've lost their faith in an afterlife, they don't feel the guilt that they might otherwise feel if they still thought "coming clean" with and thereby "corrupting" their parishioners would result in their parishioners' everlasting damnation.

You on the other hand, would not be so lucky, should you ever start to harbor serious doubts about the prospects for human lifespan extension via CR. Having serious personal doubts, but at the same time still thinking there is a chance for significant life extension via CR, and therefore hope for virtually unlimited lifespan via the LEV-driven longevity amplification effect, would leave you in an unenviable and perhaps even untenable position. You would naturally feel a heavy burden of responsibility, as you suggest in your response to the survey - "If I were to quit ... I might well have their aging and premature death on my hands".

But at the same time, as an extremely rational and compassionate person, you wouldn't want your CR advocacy to harm anyone either, should it turn out to have be mistaken or overly rosy in its portrayal. This would be especially burdensome due to the fact that there are quite a number of people who aren't as well-informed or as well-equipped to evaluate the evidence as you are, and who therefore might place a substantial amount of "blind faith" in your judgement about whether the potential benefits of serious CR outweigh the risks.

Even more troubling would be the worry that not only may these acolytes be ill-informed about the tradeoffs between risks and rewards of doing CR right, they may actually end up zealously doing it wrong (e.g. persevering too long into their senior years, not tracking their nutrient intake and/or not eating enough calories/protein, thereby compromising their muscle mass, immune system health, bone health etc..), and seriously harming themselves as a result.

In short, you'd be caught between a rock and a hard place should serious doubts about CR's efficacy ever start to percolate in your mind. As a leader, your attitude and actions get amplified as a result of their effects on your followers.

Interestingly, as of late I've thrust myself into a position not entirely unlike your own, although obviously without your considerable stature or influence within the broader life-extension community, by assuming the role of "resident skeptic" when it comes to human CR and its benefits. By your logic, I should feel seriously conflicted, since I have serious doubts about, but don't completely rule out, the possibility of substantial CR longevity benefits. It seems likely that my vocal skepticism about CR (not to mention my incessant 'Michael-badgering'...) has discouraged at least a couple people from pursuing CR with as much rigor as they otherwise might have. So if it turns out serious CR really works to significantly extend lifespan, in your words "I might well have their aging and premature death on my hands".

So why don't I too feel such a burden? Introspecting, I think it is either or both of the following:

I think both my doubts about CR benefits and my concerns about serious negative side-effects (particularly among more senior CR practitioners) have become so large that I've come to sincerely believe that the likely good I'm doing outweigh the possible harm I'm causing through my efforts to talk people out of practicing serious CR.
I feel my contributions serve as a healthy dose of skepticism to counter the general optimism, blind faith, and inertia at least a few long-term CR folks seem to exhibit around here.

In a sense, I see the two of us serving as "good cop / bad cop", counterbalancing each other and forcing others to assess the evidence for themselves, rather than relying on a single perspective, or almost as bad, no discussion at all. I readily acknowledge that I might be overdoing it at times, and my "Michael-badgering" may rub some people the wrong way (as Sthira just expressed so well here - thanks Sthira, I hear you). I also realize you do your best to show both the upsides and downsides of CR, in your own, unique style.

But from my perspective, it seems that a few folks could stand to benefit from a blunt, swift 'kick in the pants', to wake them up from their complacency and semi-blind confidence (some of which you've instilled in them, intentionally or not, through both compelling oration like your IdeaCity talk, as well as your unwavering commitment to the practice of CR over the years) that CR can't (or is at least unlikely to) do them any harm. You're not prone to delivering such a blunt message, it's not in your nature. It seems to me someone should. So I do.

I apologize if I've read entirely too much into your brief, but seemingly significant, comment on the survey. Thank you Michael for engaging in this dialog, and thanks to everyone for participating in the survey. I hope if nothing else it's been a thought-provoking exercise. It certainly has been for me.

--Dean

-----------

Description of the 10 CR Motivations included in the survey:

CR Optimism - Continued optimism that the CR primate studies were a fluke, and that the rodent CR results will scale directly to humans (i.e. 20-40% extension of remaining lifespan = 10-20 human years).
Longevity Amplification - The amplification effect discussed above which might turn a small (e.g. 2 year) life extension into something much larger.
Healthspan Extension - even if CR doesn't add extra years, it will keep us healthier during the years we've got.
Physical Benefits - We like the way CR makes us feel here and now, including things like increased energy, stamina, heat tolerance etc., regardless of what it does for our long-term health and longevity.
Appearance Benefits - Some people are happier with the way they look practicing CR. Obviously this one will depend on the severity of one's CR practice, and the weight one starts at.
Psychological Benefits - While I and others have come to question the lifespan benefits of CR relative to a healthy, obesity-avoiding diet, many of us (including myself) have always appreciated the "calm abiding" demeanor and outlook on life that long-term, serious CR seems to evoke, perhaps as a result of reduced testosterone. I hesitate to point to it, since parts are quite personal, but there is an entire thread about the topic of CR's effects on the psyche and personality, called CR Psychology - The Good, the Bad and the Ugly.
Self and Others' Perception - We've built an identity around our practice of CR, both in our own eyes, and in the eyes of friends/families/colleagues. That, coupled with the reputation we've fostered as being smart and hyper-rational, makes it hard to acknowledge we may have been mistaken, particularly when friends, family and colleagues would love to be able to say "I told you so", when/if we back away from our practice of serious CR. If we back off, we fear we'll either be viewed as having caved, and therefore are weak-willed just like everybody else, or perhaps worse, as having been wrong, which nobody likes to admit to themselves or to others.
Habit / Momentum - Many of us are creatures of habit, and habits are hard to break. Momentum keeps us going with our practice of CR, even when we have a sneaking suspicion that it may not be serving us (any longer).
Sunk Costs - We figure we've been practicing CR for so long that whatever damage (if there is any damage) to our physical body and to our social relationships has already been done, and so we might as well stick it out at this point, in hopes it will pay off.
Uniqueness / Exploration - We enjoy being different, or believe there is genuine value in exploring new possibilities, and pushing the envelope of human potential.

TomBAvoider · September 8, 2016

Thanks for the writeup, Dean, a lot of interesting info. What would've been interesting is to find out how many people started CR with the idea of CR optimism, and subsequently "lost faith", and how many never had the faith to begin with. I know I had high hopes for CR life extension back when I first read Walford's book. Back then, I'd have answered your survey very differently. But of course, we live in a different world now.

Dean Pomerleau · September 9, 2016

TomB,

What would've been interesting is to find out how many people started CR with the idea of CR optimism, and subsequently "lost faith", and how many never had the faith to begin with. I know I had high hopes for CR life extension back when I first read Walford's book. Back then, I'd have answered your survey very differently. But of course, we live in a different world now.

I agree. I suspect many people's motivations have shifted over the years. I checked all the comments people wrote in the comment box of the survey, and yours was the only one that explicitly mentioned becoming less regimented in your CR practice (e.g. when travelling) as your skepticism about CR lifespan benefits has grown.

It certainly would have been interesting to ask if people have had similar shifts, and if it equated with a growth in skepticism about longevity benefits.

I didn't mention it in my own survey response (since I was the only one who'd be reading it!), but I've gone through a similar loosening up (obviously). For example, compare what I ate on my recent Niagara Fall trips with the fact that I was so anal in 2002 that I brought all my own food in a rolling cooler on the plane when I visited WUSTL for Luigi's testing, despite the very kind and competent dietitian offering to formulate custom meals for me (and all participants) and have their well-stocked kitchen make them for us during our stay based on our usual diets.

Life is too short and there are too many interesting places to go (like Costa Rica!) to always be pinned to the same diet.

Or in the immortal words of John Lennon, "Life is what happens to you while you're busy lugging 'round your plants" - or something like that.

--Dean

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