Relation Between Body Weight and Mortality and Morbidity
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History
It has been known for some time that the relation between mortality and body weight is such that people at extreme weights -- the very thin, and the very fat -- die earlier than people of in-between weights. This led many to believe that CR doesn't work in humans. Most famous among those making such claims within gerontology is perhaps Leonard Hayflick, who, in a thinly veiled attack on Roy Walford's attempts to encourage people to try CR, claimed simply that "we know from insurance data [showing that thin people die earlier than people of average weight] that CR can't work in humans." [1] Many governmental agencies started telling us that it's "ok to gain weight as you age."
Soon, however, it was realized that there was no parallel between the overweight and the underweight. There are very few diseases that cause obesity. Yet overweight itself causes many diseases. The situations is the reverse with thinness: thinness per se causes very few health problems, yet many diseases cause thinness.
Researchers thus started to realize that the advice given to thin people to gain weight might be wrong-headed. They started controlling for diseases that lead to weight-loss, and soon discovered that instead of the U-shaped curve of the relationship between body weight and mortality, the curve they got was more J-shaped. That is, when you remove the people who are thin because they smoke or have been diagnosed with cancer, being thin doesn't look so bad. (And, thus, the advice to people should be: don't smoke, avoid other cancers, etc.; not: eat more!) It still doesn't look as good as being trim but not really skinny. But none of these studies can control for all the possible illnesses that cause weight loss. We hope that researchers will make progress on this front, however.
Problems Applying Mortality Data to the Question of Whether CR Works in Humans
Thus, no conclusions about the benefits of a CR program can be drawn from studies showing a mere correlation between weight and mortality. People trying to draw such a conclusion are basing the conclusion on a serious logical error of the form:
- If p then q.
- q.
- Therefore, p.
Example:
- If I play my guitar too loudly, then my neighbor will scream at me.
- My neighbor is screaming at me.
- Therefore, I am playing my guitar too loudly.
This is of course invalid (there are other reasons why the neighbor could be screaming at me). A valid argument would be to see that I am playing my guitar, and then conclude that the neighbor will scream at me..
In the case of the argument made about mortality/morbidity data, body weight, and CR, we have:
- If someone is on CR, they will tend to be thin.
- We have some thin people.
- Therefore, these thin people are on CR.
This is of course invalid.
CR is not about being thin. Naturally obese mice (ob/ob) on severe CR are still chubby, but live much longer than naturally thin mice not on CR. Energy-restriction shifts resources away from growth and reproduction towards repair and maintenance. The restricted weight of the organism doesn't matter.
Indeed, the assumption (or false conclusion) that "accidental/unintentional CR" is more likely to be found among the underweight is not only wrong, it may even be backwards. People in the countries where these mortality studies tend to be conducted who are naturally thin have less reason to restrict their food intake (and note: food restriction is not the same as Calorie restriction -- though that's a minor point), given societal pressures to be thin.
Ultimately, the question of the relevance of BMI-mortality correlations hinges on the percentage of thin people who are on CR. While concluding p once one has observed (or "affirmed") q is a logical fallacy (generally known, somewhat confusingly, as "affirming the consequent"), it can nonetheless serve as the basis for the generation of hypotheses. If a very large fraction of all thin people are on some version of CR, it wouldn't be unreasonable to hypothesize that CR does not retard aging. (Likewise, if there aren't that many reasons for my neighbor to scream at me, it is a reasonable hypothesis that I am playing my guitar when my neighbor is screaming at me.) However, for reasons indicated above, it seems unlikely that more than a few very thin people in the general population are on CR. Moreover, it only takes a small number of thin people not on CR (but, rather, thin because they are sick with a disease that hasn't be diagnosed, or are "naturally thin," or are heavy exercisers, etc.) to skew the mortality data appreciably.
The best way to determine whether or not CR reduces mortality is of course to look at people on CR and compare them to people not on CR. This is being done. Some initial results include those reported by Fontana [2].
See Also
References
[1] (Ref. needed)
[2] Fontana L, Meyer TE, Klein S, Holloszy JO. "Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans." Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63. Epub 2004 Apr 19.
