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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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August 29, 2012

Caloric Restriction Flops?

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Posted by Derek

Nature is out today with a paper on the results of a calorie-restriction study that began in 1987. This one took place with rhesus monkeys at the National Institute of Aging, and I'll skip right to the big result: no increase in life span.

That's in contrast to a study from 2009 (also in rhesus) that did see an extension - but as this New York Times article details, there are a number of differences between the two studies that confound interpretation. For one thing, a number of monkeys that died in the Wisconsin study were not included in the results, since it was determined that they did not die of age-related causes. The chow mixtures were slightly different, as were the monkeys' genetic background. And a big difference is that the Wisconsin control animals were fed ad libitum, while the NIA animal were controlled to a "normal" level of calorie intake (and were smaller than the Wisconsin controls in the end).

Taken together with this study in mice, which found great variation in response to caloric restriction depending on the strain of mouse used, it seems clear that this is not one of those simple stories. It also complicates a great deal the attempts to link the effect of various small molecules to putative caloric restriction pathways. I used to think that caloric restriction was the bedrock result of the whole aging-and-lifespan research world - so now what? More complications, is what. Some organisms, under some conditions, do seem to show longevity effects. But unraveling what's going on is just getting trickier and trickier as time goes on.

I wanted to take a moment as well to highlight something that caught my eye in the Times article linked above. Here:

. . .Lab test results showed lower levels of cholesterol and blood sugar in the male monkeys that started eating 30 percent fewer calories in old age, but not in the females. Males and females that started dieting when they were old had lower levels of triglycerides, which are linked to heart disease risk. Monkeys put on the diet when they were young or middle-aged did not get the same benefits, though they had less cancer. But the bottom line was that the monkeys that ate less did not live any longer than those that ate normally. . .

Note that line about "benefits". The problem is, as far as I can see (Nature's site is down as I write), the two groups of monkeys appear to have shown the same broad trends in cardiovascular disease. And cardiovascular outcomes are supposed to be the benefits of better triglyceride numbers, aren't they? You don't just lower them to lower them, you lower them to see better health. More on this as I get a chance to see the whole paper. . .

Comments (13) + TrackBacks (0) | Category: Aging and Lifespan | Cardiovascular Disease | Diabetes and Obesity


COMMENTS

1. David Formerly Known as a Chemist on August 29, 2012 2:04 PM writes...

We can't convince people to decrease their caloric intake enough to avoid becoming grossly obese, so how likely is it they'd be willing to go down to near-starvation levels to extend their lifespan? I never saw the practical application of this body of work. Who wants to live longer if you're always hungry anyway? As long as Big Macs taste good and are cheap, people will get fat and die younger. 4 billion years of evolutionary pressure taught us to eat when food is available.

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2. Anonymous on August 29, 2012 2:54 PM writes...

LDL cholesterol levels are firmly linked to reduced heart disease, which is why that's a registerable endpoint.

To my knowledge, reducing triglycerides is similar to raising HDL -- thought to be a good thing, but not universally accepted as having been proven so. (Unless you have elevated triglycerides or lipidystrophy.)

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3. billswift on August 29, 2012 8:31 PM writes...

So the comparison of the two experiments shows that underfeeding results in life extension over monkeys that over-eat, but not over monkeys that eat a normal diet. Where is the surprise there?

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4. SwedeinOsaka on August 29, 2012 8:39 PM writes...

I would be much more interested in a study that addressed intermittent fasting rather than just a decrease in calorie consumption.

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6. Anonymous on August 29, 2012 11:02 PM writes...

Has anybody seen research that addresses which type of calories to restrict?
IIRC the study was in fruitfly, and they showed that it was actually only 1 or 2 amino acids that required restriction to get the life extension effect, and you could feed a normal calorie diet with just the specific A.a.s restricted to get the effect. Lipid and carb restriction had no effect.
Always thought that maybe there is more to this story than self-flagellation by food....

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7. insilicoconsulting on August 30, 2012 2:11 AM writes...

The idea of Caloric restriction and the benefits of fasting have been around for a long long time, notwithstanding the current surge of interest.

I am not a fan of religiosity but many do advocate fasting. Other than Muslims during Ramadan, the Jain religion/sect in India for example believe in fasting throughout the year. They advocate a strict regimen with no meals or even water after sunset, a full lunch in the morning every second day...etc et.c details may vary sometimes. Their lunch in not typically rich in proteins either.

Hindus too have particular days in the year when they are supposed to fast. However with the advent of the Mac culture, many of these things are not followed.

But minority communities follow religion and thus fasting to a much greater extent.

This phenomenon is certainly worth devoting more time for study, given that these effects may be very difficult to tease out statistically. Perhaps, the Higgs hunters at CERN could use their statistical methods to give the required 0.005 LOC.

How many times have we heard conflicting results from meta-analyses and clinical trials and animal studies? vitaminD, coQ, vitamin E, chocolate etc etc.

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8. Morten G on August 30, 2012 6:57 AM writes...

The difference in the males and females is really interesting. Here's a quick literature overview of using intermittent fasting in women: http://www.paleoforwomen.com/shattering-the-myth-of-fasting-for-women-a-review-of-female-specific-responses-to-fasting-in-the-literature/
tl;dr fasting apparently gives a masculinizing response which is favourable to males but less favourable to females.

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9. Am I Lloyd peptide on August 30, 2012 8:15 AM writes...

I think caloric restriction as a general principle does work and I personally know many people who have lived long and healthy lives mainly by controlling their food intake. As the commenter above mentions though, it's hard to tease out statistically significant factors.

Ultimately, Michael Pollan's pithy one-line piece of advice is probably as good a general principle as any other for living long and healthy lives:

"Eat food. Not too much. Mainly plants."

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10. biologist on August 30, 2012 8:27 AM writes...

I was always sceptical of aging research using mice, fruit flies or C. elegans as "model organisms". The reason is that each one of these is the smallest, fastet-reproducing, shortest-life span in its group. Humans, on the other hand, are a complete outlier within Mammals: we are longer-lived than elephants! The fast life cycle of the model organisms is ideal for most lab research, but not for aging research: one would expect them to have special adaptations to their short life cycle. Therefore, it's no wonder that many aging research results cannot be transfered to large, long-lived animals.

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11. Medicamenta Vera on August 30, 2012 11:47 AM writes...

Another interesting facet to the Wisconsin study was that male rhesus appeared to outlive females. A braut and cheese effect?

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12. DrSnowboard on August 30, 2012 11:51 AM writes...

And the point of living longer is....?
Hands up those who think calorific restriction will prolong their time with the physique and mental capacity of a 28 year old rather than an 88 year old?

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13. DrE on August 30, 2012 1:41 PM writes...

#10--biologist. I agree with you there. I convinced myself of the same after some thinking about evolutionary pressures a couple of years back, when I was considering why mouse models often fail to measure up to people (who should not be confused with an especially large variety of mouse).
In any event, I am no expert in this literature, but at least two gerontology researchers predicted this years ago--see "Why dietary restriction substantially increases longevity in animal models but won't in humans" Ageing Res. Rev. 4 (2005) 339-350
Interesting that this line of thought has been ignored by all the media and many scientists. They all have been sucked into the dietary restriction fountain of youth, I suppose.

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