Putting elderly mice on a very low-calorie diet for as little as four weeks reversed many of the changes in the activity of various genes that had occurred during normal aging, according to a new study.
The research, which used a new technology to pinpoint which genes are active in mice at different ages, may help scientists understand how calorie restriction extends animals' lifespan and, eventually, to develop longevity therapies for humans.
"My work shows that calorie restriction not only prevents [age-related] changes" in gene activity, "but very quickly reverses the majority of the changes that take place with age," said Stephen R. Spindler, a professor of biochemistry at UC Riverside and an author of the study.
Huber Warner, associate director of the biology of aging program at the National Institute on Aging, said the results were interesting but needed to be confirmed. Until recently, he said, scientists have been able to examine aging's effects on relatively few genes, but the new technology enables a "vast number of genes [to] be looked at" simultaneously.
Severe calorie restriction is the only treatment that consistently has been shown to extend mammals' lifespan, although its effectiveness in people is unproven. In animals, it lowers the incidence of cancer and delays the onset of other age-related diseases. Although scientists have theorized that low-calorie diets may reduce age-related cell damage and decrease levels of cancer-promoting growth factors, they have only recently been able to examine how such diets affect many of the approximately 30,000 genes in a mouse or human.
Spindler and colleagues used a method called microarray technology to analyze which of 11,000 genes were expressed--or used to provide instructions for making proteins--in the livers of young and old mice. They also tested the effect of calorie restriction on gene expression. Some mice were fed a low-calorie diet--just enough to prevent starvation--from the time they were weaned; others were switched from a normal to a low-calorie diet for four weeks starting when they were 34 months old.
The scientists found 20 genes whose expression increased with age. Several were associated with inflammation, a process that in the liver can contribute to the development of cirrhosis or cancer. In 14 of the 20 genes, long-term calorie restriction completely or partially prevented the age-related changes.
Switching mice to the low-calorie diet at 34 weeks of age reproduced about 70% of the effect of keeping animals on a low-calorie diet lifelong, Spindler said. That suggests that if there are health benefits of calorie restriction in humans, some of those benefits could be obtained by reducing calories even in old age.