Lean Mice Have Youthful Cells

Mice on a strict diet not only live longer than well-fed animals, but they also appear to flex muscles whose cells behave much younger than their age. The findings, reported in today's Science, are the best look yet at how energy deprivation leads to healthful molecular changes in aging cells.

Scientists have known for years that mammals, including mice and monkeys, kept on restricted diets tend to live longer than their well-fed peers. Caloric restriction is "the only thing known so far that reproducibly produces such an improvement in health" in mammals, says Richard Miller, an expert on aging at the University of Michigan Medical School in Ann Arbor. Although scientists have suspected that animals that eat less might experience less damage to their cells from the corrosive byproducts of energy metabolism, what actually happens inside cells has remained unclear.

To find out how aging and diet affects cellular machinery and functions, geneticist Tomas Prolla, aging researcher Richard Weindruch, and their colleagues at the University of Wisconsin, Madison, took muscle samples from 5-month-old mice (young adults) and 30-month old mice, which are near the end of their natural life-span. The researchers dabbed the samples onto a microchip that detects activity levels of genes. They found an expected pattern for the old mice: Compared to mice in the prime of their lives, several genes that help to repair damaged genes or proteins were more active in the aged mice, while other genes that play a role in energy metabolism were less active.

In a separate experiment, the team tested muscle from mice put on a restricted diet at the age of 2 months, amounting to 76% of the calories consumed by mice allowed to eat freely. The lean mice had markedly reduced age-associated changes in gene activity; one-third of the changes were completely suppressed, while another third were partially suppressed. It seems that older animals invest much of their energy on cleaning up "the biological mess" caused by the byproducts of energy metabolism, says Weindruch. The calorie-restricted mice, on the other hand, don't need to invest as much energy in repair, he says. Thus, their genes for building proteins and other cellular components were more active than those of control mice.

The study offers the most complete look yet at changes that occur in aging cells, says Miller. If scientists could discover how caloric restriction works at the molecular level in animals, he says, they might eventually be able to mimic the effect in humans--without forcing people to go hungry.