Caloric Restriction and Life Expectancy

Highlights of the 5th European Molecular Biology Organization Interdisciplinary Conference on Science and Society -- Time & Aging: Mechanisms and Meanings; November 5-6, 2004; Heidelberg, Germany

Elena Armandola, PhD

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In This Article

CR in Primates

It seems important at this point to confront this theory with the data available on CR in humans or primates. Is there any evidence in favor or against this hypothesis? The evidence on the effects of CR on long-lived organisms (eg, primates) is scanty, although some studies have been conducted in monkeys.[6,7,8] In these studies, researchers administered a regimen associated with an approximate CR of 30% to 35%.

The results of the physiological findings in the monkeys showed great consistency with the rodent data. However, none of the ongoing non-human primate studies have experienced sufficient mortality to allow the determination of whether CR does indeed extent lifespan in these primates. Of note, preliminary data suggest that deaths due to cardiovascular disease and cancer may be reduced in the CR groups. These findings, however, are preliminary and based only on a small number of animals.

It is clear that performing studies on CR in humans presents methodological and ethical problems. For these reasons, the amount of data in humans is even scarcer. In some parts of the world, human populations have been naturally exposed to CR. Most of these populations, however, are exposed to energy-restricted diets, lacking in proteins and micronutrients. In these populations, CR is usually associated with substantial, adverse physiological effects.

The effects of prolonged CR on health and longevity in the context of an equilibrated diet have been examined in Japan.[9] A study compared data from Okinawa (where the number of centenarians is several-fold higher than in the rest of Japan) with the rest of the population. The researchers found that the total energy consumed by schoolchildren in Okinawa was only 62% of the "recommended intake" for Japan as a whole. In the adults, energy intake was 20% less than in the rest of Japan, although protein and lipid intake was about the same. The rates of death from vascular disease, malignancies, and heart disease were only 59%, 69%, and 59%, respectively, of those of the rest of Japan. The study, however, concluded that besides CR, other factors, such as genetic and environmental factors, were important in explaining these differences.

Another study was conducted to investigate the effects of long-term CR (with a good quality diet) on health and longevity in nonobese humans.[10,11] The study was conducted in 120 men of whom half were randomly assigned to the control group and the other half to the CR group. The control group was fed about 9600 kJ/day, whereas the CR group was fed about 6300 kJ/day (corresponding to a 35% restriction vs controls). The regimen was maintained for 3 years. The data showed less time in the infirmary (123 days vs 219 days) and a nonsignificant difference in the death rate (6 vs 13 deaths) in the CR group vs controls. This gives a hint that CR may affect lifespan in humans.

In all studies, the physiological effects of CR seen in short-lived animals seem to be present also in primates. For example, CR improved glucose metabolism and altered insulin sensitivity, and influenced the secretion of many hormones and the activity of the sympathetic nervous system. CR also appears to alter the gene-expression profile of cells in the muscle, heart, and brain.

CR is hypothesized to reduce oxidative damage by reducing energy flux and metabolism. The role of oxidative stress in aging is suggested by several observations: First, lifespan is inversely correlated with metabolic rate in a variety of animals, and it is directly correlated to the amount of reactive oxygen species produced; second, overexpression of antioxidative enzymes or activation of defensive mechanisms against oxidative stress retards aging and extends lifespan in some organisms; and third, CR reduces oxidative stress in various species, including mammals.

Additional factors that, however, should not be underestimated can be found in the psychosocial environment. Such factors can have a strong influence on individual well-being and can influence physiological parameters directly or indirectly modified by an appropriate diet. The effects of such psychosocial influences are more difficult to evaluate in research studies than CR and can be resistant to modification through intervention programs.

One then is left to wonder whether the isolated implementation of CR in humans, to induce maximum beneficial effects as seen in animals, is indeed a realistic possibility.

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