Calorie Restriction and an Increased Life Span

Like dark chocolate, which has been shown to lower blood pressure, red wine-derived resveratrol is a feel-good health booster. Ironically, it was a far less pleasant nutritional phenomenon that first brought SIRT1, the gene linked to aging, onto the research radar screen. Numerous studies, dating back to 1935, have shown that severe cutbacks in food intake prolong animals' lives. Known as calorie restriction (CR), the method involves carefully crafting a diet that provides ample nutrients but 30-40% fewer calories than a normal diet. Scientists have tested CR in an array of animals, from fruit flies to mice to monkeys, and, in every species, individuals on CR have lived longer than those that ate normally. Significantly, CR increases not only average lifespan but maximum lifespan, meaning that its effect is not merely to allow more animals to reach old age, but to let them reach otherwise unheard-of ages. CR animals can live as much as 30% longer than the longest-lived members of their species; in humans, this would translate to 150 years. Resveratrol is part of a broader attempt by scientists to mimic CR's effects through less drastic means.

While the mechanism by which CR operates is still being debated, in 2000 a researcher at MIT named Leonard Guarente performed a series of experiments that suggested that the SIRT1 gene plays a major role. Guarente made his breakthrough working with yeast. Using molecular biology techniques to screen for genes related to a particular trait, he identified a gene in yeast that had a strong effect on longevity. Yeast cells that lacked a functional copy of Sir2-a gene highly similar to the mammalian SIRT1-died young, while cells artificially bequeathed an extra copy of the gene were long-lived.

Further experiments showed that Sir2 is activated by a chemical called NAD, which plays an important role in the cellular breakdown of glucose. When cells are short on glucose-as they are during CR-they are long on NAD, because NAD that would normally be tied up in glucose metabolism is free to roam about the cell. Excess NAD turns on Sir2, which in turn stimulates anti-aging pathways such as the anti-apoptosis pathway described above.

To date, no scientific studies have verified whether CR makes people live longer. Such a study is hard to conduct, because it requires keeping track of a large number of people until they die. People are generally not breaking down the doors to enroll in a program that requires them to eat 1,200-1,400 calories a day (assuming a 2,000 calorie baseline-caloric needs vary widely based on gender, height and activity level), and it would take many years to get results. A recent study, however, showed that CR increases lifespan in monkeys, and a small study of middle-aged humans on CR revealed that the subjects had biomarkers, including blood pressure, heart function and levels of inflammatory proteins, typical of far younger people.

The leader of the human study, Luigi Fontana of Washington University Medical School in St. Louis, Missouri, cautioned that CR is beneficial only when the diet is designed to provide adequate nutrients. "Calorie restriction is associated with longevity only when it is coupled with optimal nutrition," he said. "On the other hand, calorie restriction coupled with malnutrition accelerates aging and causes severe diseases." While on the surface, CR and anorexia appear similar-both involve severely limiting food intake-they actually differ radically in goals, methods and outcome. CR should never be practiced without a doctor's supervision.

CR, it should be stressed, is in any case inappropriate for children, teenagers and young adults. This is because slowing the aging process involves a biological tradeoff. However CR operates on a molecular level, researchers agree that the diet switches the body from focusing on growth and reproduction to maintenance and survival. The mechanism most likely evolved as a way for animals to get through periods of famine, in large part by postponing reproduction until times were better. Kids who are still growing, as well as people who want to have babies, should not practice CR.

Sources

Wade, Nicholas. "Yes, Red Wine Holds Answer. Check Dosage." New York Times, November 2, 2006, page A1.

Wade, Nicholas. "Scientist at Work: Leonard Guarente; Searching for Genes to Slow the Hands of Biological Time." New York Times, (September 26, 2006) www.nytimes.com/ 2000/ 09/ 26/ science/ 26PROF.html? ex= 1163912400&en= 886405868974d8ce& ei= 5070.