Exercise and caloric restriction rejuvenate synapses in lab mice

Aug 02, 2010 By Alvin Powell
A photo of older, more spread-out neuromuscular junctions. Younger ones generally form tighter circles.

(PhysOrg.com) -- Harvard University researchers have uncovered a mechanism through which caloric restriction and exercise delay some of the debilitating effects of aging by rejuvenating connections between nerves and the muscles that they control.

The research, conducted in the labs of Joshua Sanes and Jeff Lichtman and described this week in the journal , begins to explain prior findings that and restricted-calorie diets help to stave off the mental and physical degeneration of aging.

"Caloric restriction and exercise have numerous, dramatic effects on our mental acuity and motor ability," says Sanes, a professor of molecular and cellular biology and director of the Center for Brain Science at Harvard. "This research gives us a hint that the way these extremely powerful act is by attenuating or reversing the decline in our ."

Sanes says their research, conducted with mice genetically engineered so their nerve cells glow in fluorescent colors, shows some of the debilitation of aging is caused by deterioration of connections that nerves make with the muscles they control, structures called neuromuscular junctions. These microscopic links are remarkably similar to the synapses that connect neurons to form information-processing circuits in the brain.

In a healthy neuromuscular synapse, and their receptors on muscle fibers 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. The resulting interference with transmission of nerve impulses to the muscles can result in wasting and eventually even death of . This muscle wasting, called sarcopenia, is a common and significant clinical problem in the elderly.

The new 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 aspects of the synapse disassembly. With exercise, we saw a reversal of most, but not all," Sanes says.

Because of the study's structure -- mice were on calorie-restricted diets for their whole lives, while those that exercised did so for just a month late in life -- Sanes cautions against drawing conclusions about the effectiveness of exercise versus calorie restriction. He notes that longer periods of exercise might have more profound effects, a possibility he and Lichtman are now testing.

Though much of Sanes and Lichtman's work focuses on brain synapses, both have investigated neuromuscular synapses for many years. Neuromuscular junctions are large enough to be viewed by light microscopy, and can be a jumping-off point for brain study, highlighting areas of inquiry and potential techniques.

"These findings in neuromuscular synapses make us curious to know whether similar effects might occur in brain synapses," Sanes says.

While the changes to the synapses through and exercise were clear in the images the researchers obtained, Sanes cautioned that their work was structural, not functional, and they have not yet tested how well the synapses worked.

Explore further: Growing a blood vessel in a week

Related Stories

Low-calorie diet: Longer life?

Apr 05, 2006

St. Louis scientists are starting a 2-year study to confirm a short Louisiana State University trial suggesting low-calorie diets result in longer life.

Laminin builds the neuromuscular synapse

Sep 15, 2008

Like a plug and a socket, a nerve and a muscle fiber mesh at the neuromuscular junction. New work by Nishimune et al published in the Journal of Cell Biology reveals that an extracellular matrix protein called laminin shapes ...

Recommended for you

Growing a blood vessel in a week

Oct 24, 2014

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

Oct 24, 2014

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments : 0