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Eldorado Desperadoes II

Molecular structure

Because of the four-plus centuries of Ottoman occupation, the folklore of all Balkan nations shares a Trickster figure named Hodja. In one of the countless stories involving him, Hodja has a donkey that’s very useful in carting firewood, water, etc –- but the problem is that he eats expensive hay. So Hodja starts decreasing the amount of hay he feeds the donkey. The donkey stolidly continues doing the chores and Hodja, encouraged by the results, further decreases the feed until it’s down to nothing. The donkey continues for a few days, then keels over. Hodja grumbles, “The bastard! Just when I had him trained to work all day without hay!”

Whenever I hear about longevity by caloric restriction, I immediately think of this story.

But to turn to real science, what is the basis for caloric restriction as a method of prolonging life? The answer is… not humans. The basis is that it appears (emphasis on the appears) that feeding several organisms, including mice and rhesus monkeys, near-starvation diets seems to roughly double their lifespan. Ergo, reasons your average hopeful transhumanist, the same could happen to me if only I had the discipline and time to do the same –- plus the money, of course, for all the supplements and vitamins that such a regime absolutely requires, to say nothing of the expense of such boutique items as digital balances.

I will say a few words first about such beasties as flies (Drosophila melanogaster) and worms (Caenorhabditis elegans) before I climb the evolutionary ladder. Many organisms in other branches of the evolutionary tree have two “quantum” modes: survival or reproduction. For example, many invertebrates are programmed to die or be killed immediately after reproduction, occasionally becoming food for their progeny. In some cases, their digestive tracts literally disintegrate after they release their fertilized eggs. Conversely, feeding an infertile worker bee royal jelly turns her into a fully functioning queen. The general principle behind caloric restriction is that it essentially turns the organism’s switch from reproductive to survival mode.

Cartoon credit: Sidney HarrisMost vertebrates from reptiles onward face a less stark choice. Because either or both parents are required to lavish care on offspring, vertebrate reproduction is not an automatic death sentence. So let’s segue to humans. Due to their unique birth details, human children literally require the vaunted village to raise them — parents, grandparents, first degree relatives, the lot. At the same time, it doesn’t take scientific research to notice that when calories and/or body fat fall below a certain minimum, girls and women stop ovulating. It also takes just living in a context of famine, whether chosen or enforced, to notice the effects of starvation on people, from lethargy and fatigue to wasted muscles, brittle bones and immune system suppression, crowned with irritability, depression, cognitive impairment and overall diminished social affect.

Ah, says the sophisticated caloric restriction advocate, but much of this comes from imbalances in the diet –- missing vitamins, minerals, etc. Well, yes and no. Let me give a few examples.

All vitamins except B and C are lipid-soluble. If we don’t have enough fat, our body can’t absorb them. So the excess ends up in odd places where it may in fact be toxic –- hence the orange carotenoid-induced tint that is a common telltale sign of many caloric restriction devotees. Furthermore, if we have inadequate body fat, not only are we infertile, infection-prone and slow to heal due to lack of necessary hormones and cholesterol; our homeostatic mechanisms (such as temperature regulation) also flag. And because caloric restriction forces the body to use up muscle protein and leaches bones of minerals, practitioners can end up with weakened hearts and bone fractures.

Speaking of fat, the brain has no energy reserves. It runs exclusively on glucose. When starved of glucose, it starts doing odd things, including the release of stress chemicals. This, in turn, can induce anything from false euphoria to hallucinations. This phenomenon is well known from anorexics and diabetics entering hypoglycemia, but also from shamans, desert prophets and members of cultures that undertook vision quests, which invariably included prolonged fasting.

So caloric restriction may make its practitioners feel euphoric. But just as people feel they have comprehended the universe while under the influence of psychoactive drugs, so does this practice impair judgment and related executive functions –- let alone causing physiological problems.

So what about those glowing reports which purport to have demonstrated that caloric restriction doubles the lifespans of mice and rhesus monkeys, as well as giving them glossy pelts? Surely we can put up with a bit of mental confusion, even failing erections, in exchange for a longer life, as long as it’s of high quality –- otherwise we’ll end up like poor Tithonus, who was granted immortality but not youth and dwindled into a shriveled husk before the gods in their whimsical mercy turned him into a cicada. And it does seem that caloric restriction decreases such banes of extended human lifespan as diabetes and atherosclerosis. Well, there’s something interesting going on, all right, but not what people (like to) think.

Flaskmouse. Photo credit: www.starshipnivan.comIn biology, details are crucial and mice are not humans. In Eldorado Desperadoes I: Of Mice and Men [See Resources], I explained at length why non-human studies are proof of principle at best, irrelevant at worst. Laboratory mice and monkeys are bred to reproduce early and rapidly. They’re fed rich diets and lead inactive lives –- the equivalent of couch potatoes. The caloric restriction studies have essentially returned the animals to the normal levels of nutrition that they would attain in the wild. Indeed, caloric restriction of wild mice does not extend their lives and when caloric levels fall below about 50%, both lab and wild mice promptly keel over, like Hodja’s donkey. In the rhesus studies, lifespans appeared extended only when the investigators counted a subset of the deaths in the animal group they tested.

On the molecular level, much attention has been recently paid to sirtuin activators, reservatrol chief among them. Sirtuins are a class of proteins that regulate several cell processes, including aspects of DNA repair, cell cycle and metabolism. This means they’re de facto pleiotropic, which should give would-be life extenders pause. As for resveratrol, it doesn’t even extend life in mice –- so the longer lives of the red-wine loving French result from other causes, almost certainly including their less sedentary habits and their universal and sane health coverage. That won’t stop ambitious entrepreneurs from setting up startups that test sirtuin activators and their ilk, but I predict they will be as effective as leptin and its relatives were for non-genetic obesity.

This brings to mind the important and often overlooked fact that genes and phenotypes never act in isolation. An allele or behavior that is beneficial in one context becomes deleterious in another. When longer-lived mutants and wild-type equivalents are placed in different environments, all longevity mutations result in adaptive disadvantages (some obvious, some subtle) that make the mutant strain disappear within a few generations regardless of the environment specifics.

When starved of glucose, the brain starts doing odd things, including the release of stress chemicals. This, in turn, can induce anything from false euphoria to hallucinations.

Similarly, caloric restriction in an upper-middle class context in the US may be possible, if unpleasant. But it’s a death sentence for a subsistence farmer in Bangladesh who may need to build up and retain her weight in anticipation of a famine. For women in particular, who are prone to both anorexia and osteoporosis, caloric restriction is dangerous –- hovering as it does near keeling over territory. As for isolated, inbred groups that have more than their share of centenarians, their genes are far more responsible for their lifespan than their diet. So does the fact that they invariably lead lives of moderate but sustained physical activity surrounded by extended families, as long as they are relatively dominant within their family and community.

Human lifespan has already nearly tripled, courtesy of vaccines, antibiotics, clean water and use of soap during childbirth. It is unlikely that we will be able to extend it much further. Extrapolations indicate that caloric restriction will not lengthen our lives by more than 3% (a pitiful return for such herculean efforts) and that we can get the same result from reasonable eating habits combined with exercise. Recent, careful studies have established that moderately overweight people are the longest-lived, whereas extra-lean people live as long as do obese ones.

So what can you really do to extend your life? Well, as is the case with many other quality-of-life attributes, you should choose your parents carefully. Good alleles for susceptibilities to degenerative age-related diseases (diabetes, heart disease, hypertension and dementia) are a great help — as is high income in a developed country with first-rate medical services, which will ensure excellent lifelong nutrition and enough leisure time and/or devoted underlings to make it possible to attend to suchlike things.

The author: Athena AndreadisAthena Andreadis arrived in the US from Greece at 18 to pursue biochemistry and astrophysics as a scholarship student at Harvard, then MIT. In her research, Athena examines a fundamental gene regulatory mechanism, alternative splicing. Her model is the human tau gene, whose product is a scaffolding protein in neurons. Disturbances in tau splicing result in dementia and cognitive disabilities.

When not conjuring in the lab, Athena writes (and used to review) stories and essays, a skill she developed as an unexpected benefit of chronic insomnia. She has always wondered about extraterrestrial life and the future of humanity. Combining all these interests, she wrote To Seek Out New Life: The Biology of Star Trek, a stealth science book that investigates biology, psychology and sociology through the lens of the popular eponymous series. She plans to write more books, if only she can find the time.

70 Comments

  1. Thanks for this article. It’s just what I was searching for. I am always interested in this subject.

  2. I think CR people to be a little ridiculous to be honest. However, it’s just another passing fad and technology is already creating far better solutions.

  3. Thanks all of you for your support! A community meeting sounds like a good idea. Let’s do it. Morris, if you’re up for helping to organize the gathering, I’ll find a server we can use.

  4. For most of its existence, humanity has remained close to starvation (which shortens life), except the top of the social pyramid. Only after the technology has surplus of almost everyone and the poor have begun to overweight from foods saturated with cornstarch will be thin is a sign of economic and social privilege – and worked outside the pale of the poor the field and, conversely, when the poor as a work in factories.

  5. An interesting point about calorific restriction being viewed in the context of your suroundings. It is all very well restricting a diet if you have the pick of what you eat. A varied diet with good exercise habits seems common sense really.

  6. I enjoyed reading the article THIS much. The whole process of aging and the modern way to find ways to overcome old age are becoming more advanced. There is something funny with age and the natural cycle of life must not be broken for anyone.

  7. I’ve always wondered why the human race waited until now to discover that almost starving helped us live longer. It seems like a round, we should have found an end long ago.

  8. here many people said almost every thing so i am thinking that what should i say about your listing and i have no more words for your post but in the last i must say your article is excellent… have a good day. Thanks

  9. I am not sure of the ethics behind my position. But if I was diagnosed with a terminal condition I would have absolutely no qualms with taking compounds that are not fully tested if their was even a remote chance there positive aspects would outweigh the negative.

  10. Our human bodies are very complex – Even today i think we have still to discover much more then we have learnt – there will never be an era that we will not learn new things about the human body

  11. Maybe a bit of normal, logical human sense would help prevent experiments which costs way too much. I mean, come on, how could a near starvation diet help someone to live longer…? lets at least put our money into experiments that seem to be possible, please.

  12. I really do not get this mentality. There are reasons to live healthy and not be lazy. Feel better. Their quality of life is better as it ages. I do not want to be a bum 300 pounds all his life. When you are 60 years and facing a knee replacement and type II diabetes, life sucks. But what kind of sick shit starve themselves so that instead of living the typical 80 or 85 years, which can live 100. I mean seriously, is the quality of life between 80 and 100 is sufficient to justify a lifetime of misery? These people are like monks behind. At least monks are doing for the next life.

    • Great info.I like all your post.I will keep visiting this blog very often.It is good to see you verbalise from the heart and your clarity on this important subject can be easily observed. registry cleaner review

  13. Everything that makes you live longer, it makes life impossible.
    Oh well, I guess the good news is that the increase in men anorexic women will mean more to ordinary men.

  14. Really great. It seems like a trick we should have figured out a long, long time ago. Thanks!

  15. I would also love to see the true study of when a moderately over weighed person has a longer life expectancy

  16. I have read many books on reduced caloric intake and its affects on the extending life. Being in the Health and Nutrition field and doing a lot of my own reading I have a hard time coming to the same conclusions, but one thing I know is the body does funny things when faced with challenges. Interesting reading.

  17. I wouldnt want to live forever … and even immortality couldnt experience everything, because he could experience sex, so any way you can not have it all. Immortality sounds terrible to me too. I bet it would be fun for a couple hundred years, and thats about it.

  18. Than you, Athena, for countering the undeserved hype this story has been getting.

    I first heard about this study on the Nature podcast, and while it was a fascinating result, even then it was made clear that its crippling effect on the human immune system alone meant that we were, at best, a long way off from getting any practical benefit. It never hurts to be reminded of the weaknesses of animal models.

  19. I know over weight people that are in their 80’s and still healthy so I am not sure how accurate this study is…

  20. Wha is meant with eldorado?
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  21. ok whats the point of immortality if you cant enjoy the finer things in life? It would be like intentionally cursing yourself if you ask me.
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  22. Scientifically is the right way to approach this kind of life extension technique and I think that it is evident that eating until full has only a detrimental effect on our overall health and is 100% not helpful in extending life.

  23. I will say a few words first about such beasties as flies (Drosophila melanogaster) and worms (Caenorhabditis elegans) before I climb the evolutionary ladder. Many organisms in other branches of the evolutionary tree have two “quantum” modes: survival or reproduction.

    • About a week ago, the Internet went wild with the announcement that a “fountain of youth” drug had been found that extends life by about 10%. I picked a site at random and read the report, knowing full well what I would find buried somewhere in the story. Sure enough, there it was, tucked at the end of a paragraph halfway down: the study was done on mice.

  24. When I first heard of Ray Kuzweil’s ideas, I assumed he was a science fiction writer. After all, the sort of transhuman future he envisioned is stock sci-fi fare. I was mildly surprised when it turns out that he is quite serious about (and well paid for expressing) his views. I was somewhat more surprised to learn that he has quite a following. Of course, I wasn’t too surprised-I’ve been around a while.

  25. While I would say that some of the possible side-effects of CR in humans, do suggest it might not necessarily extend human lifespan significantly. Supplements like resveratrol are a completely different game. Such compounds have never before been widely available in as highly concentrated and purified forms.

    When I saw, if I’m not mistaken, the ability to triple survival of human cells exposed to gamma radiation, I saw a glimpse of what such compounds could do in humans. We humans have been blessed with countless longevity mechanisms thanks to the needs of our young(for example a recent study suggested brain volume does not decrease with age in individuals with healthy brains, that is when you discount those suffering from some degenerative|diseased state.).

    Giving a boost to the repair|maintenance mechanisms may or may not do much for us, time will tell. But let’s just say the evidence, is promising, that closely related species have been seen where one is negligibly senescent(aka for all practical purposes biologically immortal, iows, ageless), and the other ages(suffers from aging). Even within some species exponential differences in lifespan of individuals exists… obviously the result of different expression patterns of mostly the same genes(same genes, due to being the same species.). This suggests that a small difference in upkeep|maintenance may be enough to confer biological immortality for all practical purposes.

  26. I’ve always found the CR people to be a little ridiculous to be honest. However, it’s just another passing fad and technology is already creating far better solutions.

  27. Well here is the thing, If humans could no longer have sex we would have to live forever or we would quickly become extinct. If we had eternity to live and no longer had to fund cancer research and so on I’m sure all time and money would be put into developing a pill that gave us the same pleasure as sex 😉 Jill Bradlie

  28. Why why why would anyone WANT to do that!

  29. While I would say that some of the possible side-effects of CR in humans, do suggest it might not necessarily extend human lifespan significantly. Supplements like resveratrol are a completely different game. Such compounds have never before been widely available in as highly concentrated and purified forms.

    When I saw, if I’m not mistaken, the ability to triple survival of human cells exposed to gamma radiation, I saw a glimpse of what such compounds could do in humans. We humans have been blessed with countless longevity mechanisms thanks to the needs of our young(for example a recent study suggested brain volume does not decrease with age in individuals with healthy brains, that is when you discount those suffering from some degenerative|diseased state.).

    Giving a boost to the repair|maintenance mechanisms may or may not do much for us, time will tell. But let’s just say the evidence, is promising, that closely related species have been seen where one is negligibly senescent(aka for all practical purposes biologically immortal, iows, ageless), and the other ages(suffers from aging). Even within some species exponential differences in lifespan of individuals exists… obviously the result of different expression patterns of mostly the same genes(same genes, due to being the same species.). This suggests that a small difference in upkeep|maintenance may be enough to confer biological immortality for all practical purposes. cna certification

  30. I don’t get this mentality. There’s reasons to live healthy & not be a slob. You feel better. Your quality of life is better as you get older. You don’t require to be some 300 lbs slob your whole life. When you are 60 & facing a knee replacement & type II diabetes, life sucks. But, what kind of sick screw would starve themselves so that than living the typical 80 or 85 years, they can live 100. I mean seriously, is the quality of life between 80 & 100 lovely to justify a lifetime of deprivation? These people are like retarded monks. At least monks are doing it for the next life.BUY XANAX ONLINE

  31. “I’ve often thought that if you could describe to women that on CR, men will improve their sexual performance but decrease their skirt-chasing behavior so they only have eyes for you, who they’re in love with, women would be like, ‘I’m cutting your calories, honey. Half your dinner tomorrow,’” April [Michael’s calorie restrictor wife] resumes.gold buyers Houston

  32. Or the third option….You can have only have sex four times, but when you do it is guarunteed to be great.. You then die immediately afterwards. You will continue to live until you select to have sex, but you will continue to age until 78, & then you will continue to live in this condition.
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  33. Neat article, reminds me of a article about feast and famine and genetic memory a while back and how they linked it to diabetics and generational linking of the gene set that mutated during a feast famine disparage from years through. And I like the reference to “Of mice and men” I read that as a book in school a long time ago. Now if we could just understand better, the genetic memory encoded in the folding and bundling of protein chains for the right chemical expressions to be further translated out. Also genetic imprinting for genetic memory or physical therapy and replacement, or even genetic imprinting for cognitive construction and such. Protein folding and chemical docking, Where is my memory enhancement going to come from first? Just 2 cents for the kettle

  34. Athena, I love the clarity and color with which you express yourself. I learn much from you.

    • Glad you enjoyed it, Joe!

      • I have read many books on reduced caloric intake and its affects on the extending life. Being in the Health and Nutrition field and doing a lot of my own reading I have a hard time coming to the same conclusions, but one thing I know is the body does funny things .

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