Finding out what makes muscles waste

We lose about 40 per cent of muscle by the time we're 80

We lose about 40 per cent of muscle by the time we're 80. Can we halt the decline? Researchers have been investigating, writes Rebecca Knowles.

New findings on muscle wasting will pave the way for improved diagnostic testing and treatment of the elderly, researchers at NUI Maynooth believe.

In a recent research project funded by Science Foundation Ireland, scientists compared young and old muscle fibres, thereby gaining new insight into the degenerative process that leads to muscle breakdown as we age.

With increased knowledge of the behaviour of aged muscle cells, future research can focus on the links between factors such as diet and exercise and the resulting retention or wasting of muscle tissue, says lead researcher Prof Kay Ohlendieck, chair of Biology at NUI Maynooth.

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Existing clinical studies have shown humans lose approximately 40 per cent of their skeletal muscle mass between age 20 and 80, making muscle wasting a significant factor in loss of independence and physical disability in old age, he explains.

The Maynooth team hopes its newly discovered "biomarkers of muscle ageing" will help prevent age-related muscle loss, improving quality of life and longevity among older people.

The use of a relatively new technique called proteomics - the examination of multiple proteins in a cell at one time - made the project unique, Prof Ohlendieck says.

"The traditional approach was to study just one gene at a time, but we looked at all the proteins in a cell at once," he said. "You can see entire pathways or whole regulatory mechanisms, so it's a global analytical method."

Using fluorescent tagging of rat skeletal muscle, researchers were able to compare the differences in protein expression between the young and old fibres.

Aged cells, they found, are under enormous stress and demonstrate a slower than normal metabolism. These changes, they concluded, are likely to be the result of a loss of connectivity between muscles and nerves.

The human body's attempts to repair those connections can lead to cellular changes, Prof Ohlendieck explains.

"The biggest insult to the ageing muscle is that disconnect, then the body starts to repair the muscle, creating slightly different forms of the same protein."

Those altered proteins provide the distinguishable difference between young and old muscle which interested the Maynooth team.

The findings also follow closely Prof Ohlendieck's earlier work exploring the relationship between the body's handling of calcium and muscle function, a common theme across a number of neuromuscular diseases.

"In a normal muscle the calcium concentration dictates the excitation/contraction process," but aged muscles suffer from calcium deficiency, inhibiting muscle function, Prof Ohlendieck says.

Importantly, the study has reinforced the complex nature of ageing and the numerous approaches that will be required to effectively combat age-dependent muscle degeneration.

In a paper that will appear in the next issue of biochemical journal Proteomics, the Maynooth team note that while "physical exercise in combination with nutritional intervention is beneficial to elderly patients suffering from moderate muscle wasting . . . such approaches are not sufficient to treat severe cases".

Prof Ohlendieck elaborates: "It's not just one gene, there's a host of factors in elderly muscle wasting, from immunology down through metabolic processes," he says. "We know that altering diet and exercise levels are helpful but, like any muscle disease, it probably also has to be treated with some drugs."