How calorie restriction and exercise inhibit several aging effects

Researchers from Harvard University have uncovered a mechanism by which calorie restriction and physical activity delay some of the effects of aging by renewing the connections between the nerves and muscles that they control.

Researchers from Harvard University have uncovered a mechanism by which calorie restriction and physical activity delay some of the effects of aging by renewing the connections between the nerves and the muscles they control.

The research, conducted in the labs of Joshua Sanse and Jeff Lichtman, both members of the Harvard Neuroscience Center and professors of molecular and cellular biology, begins to explain the initial findings that exercise and a calorie-restricted diet help stave off the physical and mental degeneration of aging. .

Their research, conducted using genetically modified laboratory mice so that their nerve cells glowed with fluorescent colors, shows that part of the aging phenomenon is caused by the deterioration of connections that nerves make with the muscles they control, structures called "neuromuscular junctions". These microscopic links are strikingly similar to the synapses that connect to neurons to form information processing circuits in the brain.

In a healthy neuromuscular synapse, the nerve endings and their receptors on the muscle fibers are in almost perfect alignment, like two hands placed together, finger to finger, palm to palm. This arrangement ensures maximum efficiency in transmitting nerve signals from the brain to the muscle, which is what causes it to contract during movement.

But as people age, their neuromuscular synapses can deteriorate in a number of ways. Nerves can contract, failing to fully cover the muscle receptors. Prof. Sans said that junctions between the nerves and the muscles can go from a continuous network that looks like a string to a network that resembles a group of beads - which break into individual blocks that are not continuous and interfere with the transmission of nerve impulses to the muscles. Loss of this activity can lead to the depletion and eventually the death of muscle fibers.

The study showed that mice on a calorie-restricted diet largely avoided age-related deterioration of their neuromuscular junctions, while those on a one-month training regimen had already begun to partially reverse the damage.

"With the reduction of calories, we saw a reversal of all these things. With exercise, we've seen a reversal of most, but not all things," Sans said.

Because of the structure of the study—the mice were on calorie-restricted diets for their entire lives, while those who exercised only did so for a month late in life—Sance cautioned against drawing any conclusions about how effective exercise versus calorie reduction is in preventing or reversing synaptic damage. He noted that longer periods of exercise could have more profound effects, a possibility that he and Prof. Lichtman are now investigating.

The study was published online by the Journal of the National Academy of Sciences and funded by grants from the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, and the Allison Medical Foundation.

Beyond this research, neuromuscular junctions are important areas to understand due to the gradual loss of muscle mass and strength, known to scientists as "sarcopenia", a common problem in the elderly, debilitating healthy people who can lose their balance and break a hip or other bones, leading to chain of physical ailments.

While the changes to the synapses through calorie restriction and physical activity were clear in the findings obtained by the researchers, Prof. Sans cautioned that their study was structural, not functional, and they had not yet examined how well the synapses worked.

For information on the Harvard University website