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How to Keep Muscles Young: Eat Less Food

Caloric restriction and exercise slow muscle decline in mice.
August 6, 2010

The connections between your nerves and muscle deteriorate with age–a phenomenon that may help explain the serious loss of muscle that often strikes old people. New evidence suggests that caloric restriction–a nutritionally complete but low-calorie diet–could help prevent these changes. According to a study published this week in the Proceedings of the National Academy of Sciences, a very-low-calorie diet, and to a lesser extent exercise, can prevent or slow some aspects of muscle decline in aging mice.

Slow decline: In young mice (top), the part of a motor neuron that releases chemical signals (green) and the receptors on the muscle that receive those signals (red) align to create a structure known as the neuromuscular junction. The overlap between these two components is shown as yellow. As the animals age (bottom), the structure begins to deteriorate.

The researchers hope that the findings will point toward new ways to stem loss of muscle mass, one of the most common problems of aging and a major cause of injury. They also say it could help them understand how similar factors affect neural connections in the brain. “Much of the research on aging in the nervous system has been done in the context of neurodegenerative diseases, such as Alzheimer’s,” says Joshua Sanes, a neuroscientist at Harvard Medical School and one of the senior authors of the study. “Remarkably little is known about the basic phenomenon of aging in the nervous system.”

The researchers studied the structure of the neuromuscular junction–the connection between the motor neurons and muscle–in mice that had been genetically engineered to make these neurons glow. Because these junctions are relatively large and tend to have a regular structure, it is easy to see when things go wrong. When the mice were about two years old, roughly the equivalent of a 70- to 80-year-old person, the junctions had clearly deteriorated. “The majority of muscle fibers had abnormal junctions,” says Jeff Lichtman, a neuroscientist at Harvard University and a senior author of the study. The connections were generally smaller, and the nerves and corresponding receptors on the muscle, which are normally aligned, were askew. “They looked old and decrepit, kind of like a person looks old,” says Lichtman.

The findings, hinted at in previous research, could shed light on a major health issue in aging: sarcopenia, or loss of muscle mass. “That is one of the most robust age-related impairments observed across many species, but it’s not really clear what causes it,” says Charles Mobbs, a neuroscientist at Mt. Sinai School of Medicine, in New York, who was not involved in the research. “This study provides evidence that an important mechanism involves neuromuscular junctions and the role of motor neurons.”

To look for factors to stem this decline, the researchers examined animals that had been on a restricted diet most of their lives. This type of diet has previously been shown to extend lifespan in a number of species and to reduce some signs of aging, such as diabetes and heart disease, in some animals. “With caloric restriction, we saw a striking absence of abnormalities,” says Lichtman. “These animals’ synapses looked quite young.”

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

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