Researchers at Harvard University in Boston, US, have uncovered a mechanism through which caloric restriction and exercise delay some of the debilitating effects of ageing by rejuvenating the connections between nerves and the muscles that they control.

The research, conducted in the labs of Joshua Sanes and Jeff Lichtman, both members of the Centre for Brain Science at Harvard and professors of molecular and cellular biology, begins to explain prior findings that exercise and restricted-calorie diets help to stave off the mental and physical degeneration of ageing.

Sanes said their research, conducted through laboratory mice genetically engineered so their nerve cells glow in fluorescent colours, shows that some of the debilitation of ageing is caused by the deterioration of connections that nerves make with the muscles they control, structures called neuromuscular junctions.

In a healthy neuromuscular synapse, nerve endings and their receptors on muscle fibres are almost a perfect match, like "two hands placed together, finger to finger, palm to palm". This lineup ensures maximum efficiency in transmitting the nerve’s signal from the brain to the muscle, which is what makes it contract during movement.

As people age, however, the neuromuscular synapses can deteriorate in several ways. Nerves can shrink, failing to cover the muscle’s receptors completely. Sanes said the intersections between the nerves and muscles can go "from a continuous network that looks like a pretzel to one that resembles a bunch of beads — broken into discontinuous individual lumps, interfering with transmission of nerve impulses to the muscles". This loss of activity can result in wasting and eventually even death of muscle fibres.

The work showed that mice on a restricted-calorie diet largely avoid that age-related deterioration of their neuromuscular junctions, while those on a one-month exercise regimen when already elderly partially reverse the damage.

“With calorie restriction, we saw reversal of all of these things. With exercise, we saw a reversal of most, but not all,” said Sanes.

“There’ve been quite a few reports that caloric restriction and exercise delay cognitive decline, but people don’t know much about the cellular reasons behind them.”

“These findings in neuromuscular synapses make us curious to know whether similar effects might occur in brain synapses.”