The findings are among the first to show that caloric restriction has a robust effect on the nervous system, which has been a matter of debate. "This paper demonstrates the protective effect of dietary restriction on muscle and the neurons that regulate muscle function," says Mobbs. "It's one of the most convincing papers I have seen demonstrating a protective effect of dietary restriction in neural function."

Those who are disinclined to diet for their whole lives still have hope, however. Mice that exercised for a month in old age also had healthier neuromuscular junctions, though the findings weren't as significant as those for caloric restriction. "Just a month of exercise actually seemed to reverse the course of the downward spiral," says Lichtman.

"If there were ever two scientists who did not want to hear this result, it's us," says Lichtman, of himself and Sanes. "We don't love to exercise, and I find it real torture to starve myself." Because few people want to or are able to maintain a severely restricted diet, scientists and drug developers are searching for molecules that can mimic these health-boosting effects.

Others say the study gives reason for optimism. "The effects are remarkable, given the short time span and late onset time of exercise," says Leonard Guarente, a biologist at MIT who was not involved in the research. "It suggests it's never too late."

It's not yet clear how well the findings will translate to humans. Exercise has been shown to have health benefits for older people, but "many studies demonstrate that exercise cannot restore muscle to the same functionality that a young exercised muscle would have," says Mobbs.

The researchers are now searching for the molecular basis for the decline of neuromuscular junctions, as well as for the benefits of caloric restriction and exercise. "Is there some key molecule that goes away so the synapse falls apart?" says Sanes. "Is it the nerve's fault and muscle is fine, or vice versa? We won't be able to find out [how caloric restriction helps] until we know the normal mechanisms of age-related decline."

It's also unclear whether the two treatments work via the same mechanism or different ones. "I believe that caloric restriction is fundamentally affecting the processes of aging, whereas exercise training doesn't really do that," says Russell Hepple, a scientist at the University of Calgary, in Canada. "An exercise-trained muscle is definitely happier than a sedentary one, but it's not going to affect the processes of aging like caloric restriction does."

Researchers hope ultimately to apply the same approach to study nerve connections in the brain, which is more difficult because these nerves are much smaller and more densely packed. Previous research suggests that the number of connections declines with age, and that caloric restriction can help stem memory loss in older mice.