Aubrey de Grey and Calorie Restriction
Permalink | View Comments (11) | Post Comment | | Posted by Reason

It's no great secret in the healthy life extension community that biomedical gerontologist Aubrey de Grey - the driving force behind the Strategies for Engineered Negligible Senescence and half the driving force behind the Mprize for longevity research - doesn't think that calorie restriction (CR) is a practical strategy for extending life span to any significant degree in humans. Which isn't to say that he thinks calorie restriction is no good - it's quite clear from ongoing studies that the health benefits are very impressive. April Smith's recent post on the subject is worth reading. Aubrey comments:

For the avoidance of doubt: though I think that CR will probably give humans only 2-3 years of extra lifespan at most, I certainly don't disapprove of it -- the health benefits are clear, as shown in the Holloszy and Fontana work, and even 2-3 years may make a big difference to quite a lot of people. So I approve of CR.

Discussions on the efficacy of CR in extending human life span are a touchy subject in some quarters - but science is science and will keep moving forward towards a definitive answer to match what we know about CR and life span in smaller mammals. You can find Aubrey de Grey's paper explaining his view on CR at his website. As April tell us, Michael Rae - noted CR practioner and also Aubrey's research assistant these days - has penned a rebuttal to that paper that awaits publication:

MR wrote a rebuttal to Aubrey's article about weather and CR that was accepted by Gerontology, but he had to withdraw it due to page charges. Now he's resubmitted it to another journal and is waiting for approval.

I'm looking forward to seeing it; Michael writes a good paper when he sets his mind to it. You can see some of his work at the Longevity Meme and here at Fight Aging!

Comments

What a trade off: feeling hungry your whole 80+3 years, or just enjoy your meals and die at 80...

Posted by: Berend de Boer at August 4, 2005 3:07 PM

What seems to be lacking in the discussion of CR's benefits is mentioning of the curve-squaring phenomenon: 80+3 years of hunger might be better than 80 years of pizza, if those 80+3 years are largely cancer, heart disease, and diabetes free. Of course *something* has to kill CR people eventually. But my impression is that CR squares the curve, so that animals remain quite healthy until they die, and then when researchers autopsy them they look "clean" on the inside. If this is true in humans too, 80+3 years of hunger might not be so bad.

Posted by: Kip Werking at August 4, 2005 3:40 PM

For the journal-ignorant, like me -- what does "page changes" mean?

For some set of assumptions (also dependent upon one's age) about when takeoff velocity is reached 2-3 years is a tremendous underestimate. Don't know how large that set is for a given age.

Posted by: Mike Linksvayer at August 4, 2005 10:06 PM

Aubrey is correct about CR and its limitations, but offers us little understanding why this should be the case. I have written a short paper intended for the journal Functional Ecology addressing last year's paper by Kozlowski and Konarewski appearing in the Forum section of that journal, said paper being dismissive of mathematical biology's quarter power scaling and its relevance to biology. Dr. John Speakman said the K&K paper was scathing for quarter power scaling and its alleged relevance. My response, submitted to the Forum, was rejected for lack of citations and the undertone of disdain for a biology that has yet to see chemical/biological energy as a phenomenon involving electromagnetism and not understandable in thermodynamic terms. The response points out how the secret to longevity easily attainable lies in metabolic rate and the effects on that rate resulting from changes to metabolic efficiency resulting from the clinical application of electrochemistry to trigger nervous system trophism. The response invokes a redox coupling between stomach and nervous system, and suggests that energy capture by a multicellular organism from food sources may be supplemented through the guided discharge of a battery to the site of the peripheral nerve endings. Analysis of the mathematcs suggests that healthy lifespans may be easily extended to well over 150 years with this simulation and supplementation of nervous system trophism. The paper is in microsoft word and available upon request from gokelly@charter.net.

Posted by: GCOKelly at August 7, 2005 11:02 PM

I would like to add that the response touted by me explains why, in mathematical terms, CR does not work on large mammals. This explanation conflicts with the account offered by Dr. Lloyd Demetrius of Harvard in his paper "Caloric Restriction, Metabolic Rate, and Entropy" publishd last year in the Journal of Gerontology. Dr. Demetrius fails to grasp the completeness of the equation he cites in his paper, what has been termed the master equation of biology which relates metabolic rate to metabolic efficiency and body mass, and which is concordant with the idea that increased metabolic rate translates to increased life span potential. Dr. Demetrius introduces other variables, like species entropy and directionality theory, in the mistaken notion that the master equation is not enough. Dr. Demetrius has never run the numbers on that master equation, nor does he understand that CR increases metabolic efficiency (a ratio of rate of ATP synthesis to rate of electron flow from food sources) by diminishing the denominator, the rate of electron flow from food sources.

Posted by: GCOKelly at August 7, 2005 11:18 PM

The previous comment is a good example of how not to go about this science thing. See "the seven warning signs of bogus science" as line items you should avoid if you want to engage the scientific community:

http://chronicle.com/free/v49/i21/21b02001.htm

Posted by: Reason at August 7, 2005 11:20 PM

Thank you, Reason, for cautioning others about how not to go about 'this science thing.' But you should keep in mind that these are WARNING signs, and do not legislate against the validity of the material. Anyone familiar with the work of the people mentioned would know that: John Speakman of Aberdeen University supports the idea that increased metabolic rate translates to longer life, contrary to long-accepted accounts that high metabolic rate means short life span; Lloyd Demetrius also holds this as the case; and it is the contention of Dr.'s West, Brown, and Enquist (of the University of New Mexico and Los Alamos), who have made quarter power scaling such an important part of mathematical biology. This is a relatively new area of biology, and there is still a great deal of disputation about whether body mass scales exponentially by 2/3 or 3/4 when considering matters of energy distribution in an organism or biological system. The paper proffered is an attempt to explain, by means of mathematical analysis, why, if life span potential is a consideration, metabolic rate is NOT basal metabolic rate, and mitochondrial efficiency is NOT metabolic efficiency, with basal metabolic rate scaling exponentially to the 2/3 power of body mass, while METABOLIC RATE, which is the rate at which the organism captures and distributes energy from food sources, scales to the 3/4 power of body mass.
It just so happens that West, Brown, and Enquist, in their discussions of the model, not the mathematics, say it describes the distribution of ENERGY born by an organism's vascularity. The criticism of Kozlowski and Konarewski is that the math is irrelevant because the model is misleading, its biggest weakness being the invariance of size of capillaries across species, and how this limitation prevents activity, which depends upon higher metabolic rates than those that are basal, from being accounted for. What the proffered paper suggests is that this limitation can be avoided if instead we treat the nervous system as the deliverer of energy harvested from food sources in an act of electrochemical chemoheterotrophism rather than blood flow. The latter delivers chemicals, but not energy. When I asked Dr. Speakman to review this paper, which was in keeping with the increasingly accepted notion that energy levels are the key factor in aging, he responded that things must be really boring in the world of physics. When submitted to the journal Functional Ecology I was told by the editor that there were not enough citations. He never said how many were enough. The work, being original, did not have many papers to cite, and focused on a study of the numbers and their implications, a study the likes of which is available nowhere. Dr. West, who has almost singlehandedly made mathematical biology a contender in the world of biology, is a physicist. Speakman, Kozlowski, and Konarewski are biologists who resent what they see as they encroachment of physics on the world of biology, a study they want to keep special in view of its subject matter. And that is why they all claim that the seeming ubiquity of West's quarter power scaling is based upon a flawed model and has no relevance whatsoever for the study of biology. What I show in the paper is that the flaws in the model can be corrected, but the mathematics are right on target. I am faced with telling West, Brown, and Enquist that their model is wrong, but their mathematics is correct, and with telling Speakman, Kozlowski, and Konarewski that their premature dismissal of quarter power scaling is shortsighted, that the physicists are onto something very important. I am ignored by both sides.
Thank you for poisoning the water. I would like to point out that success in 'this science thing', if you are familiar with the history of science, has never been dependent upon formulaic approaches to methodology. Indeed, Max Planck observed that science advanced with each funeral because of the heat he took over the idea that energy was quantized. Einstein, who, 100 years ago this year, published the papers that would make him famous in the world of theoretical physics, chose to remain working in the patent office for several years more. He was convinced that in the academic world the pressure to publish contributed to superficiality. And it is superficiality I see everywhere. Dr. Demetrius, who received his Ph.D. from the University of Chicago in the 1960s, postures now as a mathematical biologist, yet he has never run values for the variables in the quarter power scaling equations he cites. If he had he would know why Caloric Restriction does not work on large mammals, and it has nothing to do with the entropy of species, said entropy addressing litter size and percentage of time in life span during which an organism can reproduce. I have not encountered one biologist who understood electromagnetism, was told by an emeritus professor of microbiology that electromagnetism had no relevance for biology despite its concern with the role of the electron in chemistry and as the bearer of energy, and was told by a retired neuroscientist that the neurophysiological definition of electricity was 'beyond the scope of physics.' Sure as hell this is superficiality. I am convinced now that this superficiality extends to the sciosophists who moderate this site, who tout Aubrey de Grey as an expert despite his lack of specifics and vague pronouncements about the effectivenss of caloric restriction.

Posted by: GCOKelly at August 8, 2005 2:37 PM

I rest my case. Whatever the merits of your material, you are approaching the subject here in a way that is unhelpful to your cause.

You may find some of the scientific types at the Immortality Institute willing and qualified to critique and/or discuss your work:

http://www.imminst.org/forum/

Posted by: Reason at August 8, 2005 3:32 PM

It would seem that the greatest problem CR presents to de Grey's SENS approach is a short-term competition -- a method of achieving some semblance of life extension without waiting for the gifts that science and nanotechnology may present to our grandchildren.

The "plus three" argument in and of itself is a bit misleading as well: most people that approach any sort of diet are pretty unhealthy to begin with -- so the inference that adapting the CR approach to food-intake will give me just a couple more years than retaining my extra poundage and the eating fast-food and beer will . . . even if CR turns out to be crock, that inference is patently untrue.

Posted by: aexapo at August 25, 2007 1:51 PM

There's another aspect to what is being called the "+3" conclusion drawn by Aubrey. One poster mentioned that with calorie restriction, one could only hope to live to "80+3" years. However, I think Aubrey refers to an increase in *maximum* lifespan of +3 years - and "maximum human lifespan" is currently defined as "the oldest recorded human" - 122 years. So the 80+3 argument greatly underestimates (by over 50%) one's potential lifespan with calorie restriction. In contrast, I understand Aubrey to be saying that caloric restriction will "only" get you to 125 years, maximum (122, "+3").

Here is an interesting point about the "persistent hunger during life" argument. I practice CR (when I can stick to it), and I often struggle with feelings of hunger. However, I have learned to compare "lifetime hunger vs. maximum lifespan" in a different way. I think that by not doing *everything* I can to *maximize* my lifespan, I increase the likelihood that I "miss the boat" for longevity therapies. That is, if one assumes that anti-aging therapies that greatly extend lifespan *will* come into existence at some point, the only problem is that one must *survive* until these therapies exist. So yes, hunger may be frustrating, but I imagine the day when I don't have to worry about counting calories because interventions exist to repair the damage done by metabolism. So the practice of CR can be a way by which to *maximize* the chances of surviving until the time that rejuvenation therapies exist. And at *that* time, one can relent on the strict diet and enjoy food a bit more, along with so many other things.

I developed this way of thinking about CR, hunger, and lifespan from reading interviews with Michael Rae, in case anyone is interested.

Posted by: Max Peto at April 10, 2009 11:44 PM

If you're eating a diet of pizza and fast food, you're life span won't be 80 years, it will be more like 40-50 years. And those years will be miserable because you will be suffering from diabetes/heart disease/cancer, etc.

Caloric restriction not only extends MAXIMUM lifespan, it also greatly reduces the incidence of disease.

The Okinawans are a great model, because of their diet and lifestyle, the earlier generations saw a lifespan of over 100 years. Unfortunately their children have adapted to an American lifestyle/diet and are dying before their parents/grandparents.

If you're young (under 50) and follow caloric restriction/healthy diet and lifestyle, that alone might give you a lifespan of 100-120 years. And if these therapies that De Grey has proposed are possible, then a lifespan of 1000 years might be possible for those under 50 if they follow the above.

However, don't hope to live forever. Even stars die. Accept death and enjoy your life.

Posted by: Otis at April 16, 2012 6:20 AM
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