CRAN DIET

Fred Ringel sent us a clipping from HARVARD MAGAZINE. It questions some of the claims that Calorie Restric-tion (CR) proponents make.

Research on rats and mice has shown that reducing their food consumption by 50 percent, while maintaining adequate nutrition, can lead to a 30 percent increase in longevity. Because the human mean life span in the United States is 75 years and the maximum life span potential is 120 years, CR might add 15 and 20 years, respectively, to those numbers, But will what works for mice also work for men?

Lloyd Demetrius, an associate of the department of population genetics in the Museum of Comparative Zoology, writes in the current issue of the Journal of Gerontology that the answer lies in understanding just how (CR) acts m an organism to extend its life, Traditionally, CR has been thought to work by lowering the metabolic rate, the rate of oxygen consumption, This "rate of living" theory, as it is sometimes called, was advanced in 1928 by biostatistician Raymond Pearl, who observed the effects of CR on domestic animals. Extrapolating from a very small sample, Pearl argued that metabolic rate determines longevity, and the slower the rate of metabolism, the longer an organism will live, In 1954, Dr, Denham Harmon. proposed a mechanism to explain how the rate of living theory might work, postulating that oxygen radicals cause damage resulting in aging and death. This gave "a certain molecular respectability" to Pearl's idea, Demetrius says.

But the empirical evidence does not support Pearl's theory: antioxidant supplementation does not increase longevity. Some birds with twice the rate of metabolism of equivalent-size mammals, which should live half as long, instead live at least three times longer. Furthermore, Pearl's qualitative theory predicts that CR should reduce the metabolic rate across all living species.

But in some experiments, CR has had no effect on metabolism, and might even increase it. If a slowed metabolism is not the reason mice and rats on a restricted diet live longer, how can the phenomenon be explained? Demetrius believes he has the answer, he feels that human beings will respond differently to caloric restriction than rats and mice do. A mathematical biologist, Demetrius argues analytically that the rate of aging is determined not by metabolic rate but by metabolic stability, which is a measure of a cell's ability to maintain stable ratios of certain critical cellular metabolites in the face of stress.

In order for a cell to perform its function," he says, it must maintain the ratio of these cellular metabolites within a certain range." Otherwise, the cell's function is compromised. CR increases metabolic stability. An organism's metabolic stability, he argues, is determined by its evolutionary history, so researchers can predict what the metabolic stability of a species will be if its history is known - and hence predict just how much CR might extend its life.

Mice and rats, for example, are "opportunistic species," says Demetrius. They experience periods of relative food abundance punctuated by prolonged periods of scarcity, and therefore undergo episodes of rapid, exponential population growth followed by periods of decline.

The bad news or perhaps good news (depending on your fondness for food) is that your already high metabolic stability means CR will not lead to dramatic life extension, as it does for mice Demetrius predicts a one to five year gain in human life span, largely attributable to reductions in rates of cardiovascular disease and diabetes.

Mice, with their low metabolic stability, have "lots of room for improvement." Demetrius cautions that studies on ca-loric restriction and longevity were, done on healthy-weight animals. Being obese is not healthy. "Drastic changes in the eating habits of healthy-weight individuals," he says, will not make any critical difference in longevity."

We asked that most famous CR practitioner, CI President Ben Best, what he thought of all this. His reply:

I hate to sound harsh, but Dr. Demetrius should stick to mathematical biology, because he fails to understand many basic facts of gerontology. First, Pearl's long-discredited "rate of living" theory is not equivalent to the free radical theory of aging. Birds live more than twice as long as mammals the same size partly because their mitochondria are more efficient -- produce fewer free radicals. The rate of living theory does not account for more efficient mito-chondria, better DNA repair, better insulin control and many other factors.

Antioxidant supplements do increase longevity in the sense of average life-span, even though antioxidants do not increase maximum lifespan. Both calorie restriction and the longevity of birds is compatible with the free radical theory of aging, because those practicing calorie restriction also have more effi-cient mitochondria. Antioxidants are limited in their effectiveness partly be-cause the body has homeostatic mecha-nisms that reduce antioxidant enzyme production when external antioxidants are introduced. It is far better not to produce free radicals in the first place (by calorie restriction, efficient mitochondria) than to try to quench them once produced (an ounce of prevention is worth a ton of cure).

Nonetheless, the best hope for longevity treatment in the next few years is substances that will increase the body's production of natural antioxidant enzymes. I wouldn't categorically exclude the claim by Dr. Demetrius that maintaining ratios of critical metabolites is important, but I have not heard this theory before and the details would need to be ex-plained before I could give it more credence.

 For more detail on Mechanisms of Aging, see: http://www.benbest.com/lifeext/aging.html

Ben Best