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A hunger to live longer

Want to live a long time? Who doesn’t? Quite a number of smart people have staked their hopes for long life on restricting their calorie intake. It’s an idea that rests on a not inconsiderable body of evidence. But some new developments suggest it may be a questionable strategy.

The idea that a diet containing a very modest energy content (measured in Calories or Kilojoules) could dramatically prolong lifespan is based on one of the most replicated findings in all of biology.

As long ago as 1935, researchers reported that lab rats fed dramatically restricted diets lived up to twice as long as rats allowed unrestricted access to food. The lifespan extending effects of dietary restriction appear to come about by delaying the onset of ageing and slowing the cellular damage and onset of diseases like cancers that naturally occur with age.

Since then, similar results have been obtained in mice, Rhesus monkeys, zebra fish, vinegar flies (Drosophila melanogaster), the nematode worm (Caenorhybditis elegans) and even yeast. The fact that dietary restriction prolonged lifespan and slowed ageing in such a variety of organisms strongly suggested that the underlying mechanisms are shared by all animals and possibly even all eukaryotes - the large group of complex organisms that includes animals, plants and fungi.

It didn’t take long for people to spot a potential route to slowing ageing and putting off the inevitable. Roy Walford championed what he called CRON - Calorie Restriction with Optimal Nutrition - in Beyond The 120-Year Diet. He argued that cutting dietary energy while maintaining micronutrient intake would prolong normal lifespan to well over a century, reducing the incidence of the major diseases of aging.

We are not talking here about avoiding overeating or gluttony, but rather about cutting 20 to 40 percent from the energy content normally recommended to maintain a healthy body mass. Walford was among the founders and the chief scientific luminary of the Caloric Restriction Society, the most prominent of many organisations devoted to promoting health through dietary restriction. There are books, and Internet forums and even on-line tools like Interactive Diet Planner and the puntastic CRON-O-Meter calorie tracking software.

While dietary restriction seems to have a lot of scientific evidence in its favour, that evidence remains largely circumstantial. It takes decades to verify predictions of dramatically enhanced longevity. And long-term randomised controlled trials are impossible for a restrictive diet that, according to some detractors promotes “a longer life, not worth living”.

So the case for dietary restriction rests largely on several short-term studies in humans and the evidence that dietary restriction promotes longevity in a wide variety of organisms.

The problem is that a great many studies in a variety of animals show little or no positive effects of dietary restriction on lifespan or ageing. In a recent meta analysis published in Aging Cell, The University of Otago’s Dr Shinichi Nakagawa and his collaborators showed that while dietary restriction significantly increased lifespan across 36 species and 145 studies, the effects were less than straightforward.

First, dietary restriction had more dramatic positive effects in laboratory “model” organisms - like Drosophila, mice, rats and C. elegans - than in non-model species. The truly eye-catching studies in the big journals like Nature and Science are more often on the model species, whereas the null results on animals that fewer people are interested in tend to be in specialist journals.

On top of this, dietary restriction tends to have larger positive effects on females than on males. This makes sense because a constrained diet probably slows down costly female reproduction (gestation and egg-laying) more dramatically than less costly male reproduction. The costs of reproduction are an important determinant of ageing and longevity.

Last, where dietary restriction had positive effects, these were more closely related to restricted protein intake rather than restricted overall energy (caloric) content.

Nakagawa’s findings echo what Sydney University’s Stephen J. Simpson and Massey University’s David Raubenheimer said back in 2007. That while there is plenty of evidence that dietary restriction has positive effects in lab animals, the most important details have yet to be worked out. These include whether the restricted diets work by eliminating calories or by avoiding costly excesses of protein or other nutrients.

The fact that dietary restriction tends to work most dramatically in laboratory models suggests the effect might be more about adaptation to laboratory conditions than a general response shared by all animals. Humans, with agriculture, technology and the ability to escape from hunger might be more similar to lab rats than wild mammals. But then again they might not.

This is an area of research that has a long way to go yet, but things are certainly being shaken up and that can only be a good thing if we are to gather useful knowledge about how to delay ageing and prolong life. I am sure the most cult-like practitioners of caloric restriction won’t change their lifestyle, but it is possible they’ve been reducing the wrong nutrients.

For now, I see no reason to put myself on a dramatic calorie-restricted or protein-reduced diet. Especially given what Simpson and Raubenheimer’s research tells us about the importance of protein in avoiding overeating.

Join the conversation

9 Comments sorted by

  1. Robert Peers

    General Practitioner

    Dr Luigi Fontana's bunch of middle-aged calorie-restricting men in the USA do seem to show anti-ageing effects in their cardiac function, so we can't discount the possibility that caloric restriction (CR) might extend healthy life-span in humans. However, to be really sure of getting to 100 in good shape, a better approach than CR--that is far more sneaky, and also easy for females to follow--is hinted at in the title of Mr Dan Buettner's waffly book on life extension: "Blue Zones: Lessons for Living…

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    1. Paul Rogers

      Manager

      In reply to Robert Peers

      Health benefits and deficits can never be attributed to one nutrient or constituent of diet. The system is too complex, with genes, physical activity and dietary habits contributing to overall health and longevity.

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    2. Emma Anderson

      Artist and Science Junkie

      In reply to Paul Rogers

      That may be true, but a food intolerance and allergy can be attributed to a specific protein (usually) interacting with those complex, interconnected systems.

      Also, when the author mentioned that the costs of reproduction are a determinent in the ageing process, I had a thought that some aging related cancers might be more common in women who have not had children. Might sound counter intuitive, but bare with me. The cost of reproduction in women is probably the ongoing replenishment of the…

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    3. Robert Peers

      General Practitioner

      In reply to Paul Rogers

      In reply to Paul Rogers:

      Here are some single nutrients, deficiencies of which cause serious disease--vitamin A [dry eyes/blindness], vitamin C [scurvy], thiamine [beri-beri], niacin [pellagra], iodine [cretinism], iron [anaemia], vitamin D [rickets], vitamin B12 [megaloblastic anaemia].

      As for dietary constituents, let's take two simple, but potent causes of serious disease:

      1. Saturated fat [dietary ratio of polyunsaturated to saturated fatty acids much below 1.00]. Sources: dairy fat…

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    4. Paul Rogers

      Manager

      In reply to Robert Peers

      Mr Peers, I am well aware that nutrient deficiencies are precursors to disease, that's why we have official nutrient reference values (NRVs). What I suggested is that even if you get this right (comply with recommended nutrient intakes), you still have other factors to contend with, eg, genes and lifestyle characteristics like physical activity, pollution etc.

      Inositol will not be a magic bullet, unless you can point me to anti-ageing effects of this substance in humans, or perhaps a similar mammalian species. Even then, many other factors come into play in real life. In any case, I don't think the worms cut it.

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  2. Paul Rogers

    Manager

    Nice summary, and I agree with the general sentiments.

    I note that recent cohort studies point to increasing mortality with low-carbohydrate, high animal protein diets, so animal protein in particular may not only increase mortality through increasing energy intake excessively, as you suggest, but by associated causal factors.
    http://www.ncbi.nlm.nih.gov/pubmed/20820038

    I have speculated that high levels of physical activity may simulate calorie restriction to some extent, perhaps by affecting favourably glucose and cholesterol levels as well as 'healthy' low BMI. (Cohort studies of mortality, morbidity and BMI get confounded by low BMI due to poor health.)

    BTW, Roy 'doc' Walford died of MND/AML (motor neurone disease / amyotrophic lateral sclerosis) at the age of 79.

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  3. Yolanda Newman

    Learning support coordinator

    Whilst how to live longer is interesting, I am more intrigued by the question of why. My experience of life is that it is not much fun unless lucky enough to have happiness in childhood and good luck in adult hood. I will be glad when it is the end personally.

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  4. Tim Scanlon

    Debunker

    The study I read recently, the author was on the radio (Radio National) talking about calorie restriction and how no one could maintain the level of restriction required. Thus the idea of that being a method to prolong life was flawed. She also mentioned that it was flawed for two reasons: first you couldn't stick to it, second it made you miserable so your quality of life was terrible.

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  5. Sean Lamb

    Science Denier

    My understanding - alas sans references - that general health markers (although which precisely I am not sure) improved in Britain during the period of rationing.

    Straying a bit from the topic, this paper (which some think has question marks over) seemed to show interesting life extension just with olive oil.
    http://retractionwatch.wordpress.com/2012/06/28/controversial-paper-on-life-extending-buckyballs-corrected-after-blog-readers-note-problems/
    My own belief that if the buckyballs are having an effect, it will only be through mediating serum lipid levels and content (being rather hydrophobic and hence coated in fatty acids). Probably the first step for the researchers interested in buckyballs is to find a delivery composition that it is survival neutral. All this is a bit of stretch on the back of a paper with dodgy image practices.
    Although perhaps this points in the same direction
    http://www.ncbi.nlm.nih.gov/pubmed/21472381

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