Drugs May Revive Ageing Muscles, Study Suggests

Drugs could one day be used to reverse the muscle-wasting effects of ageing, new research suggests.

Scientists have identified a key process responsible for muscle weakening in old age and used a chemical to block it in mouse studies.

The findings could pave the way to body-building anti-ageing drugs that keep people strong and fit near the end of their lives.

A team of British and US researchers looked at the way stem cells in muscle repair damaged tissue by dividing and developing into numerous new muscle fibres.

Strenuous activity, such as lifting weights, results in minor damage that triggers this response and builds up muscle. The end result is bulging biceps and rippling torsos.

But as people age, muscle loses its ability to regenerate itself, leading to limbs that are puny and weak.

Studying old mice, the researchers found that the number of dormant stem cells in muscle reduces with age.

They traced the effect to excessively high levels of FGF2 (fibroblast growth factor 2) - a protein that stimulates cells to divide.

In ageing muscle, the protein was continuously awakening the dormant stem cells for no reason. The supply of stem cells depleted over time, so not enough were available when they really were needed. As a result, the ability of muscle to regenerate was impaired.

The scientists found that a drug that inhibits FGF2 prevented the decline of muscle stem cells.

Treating old mice with the drug, called SU5402, dramatically improved the ability of aged muscle tissue to repair itself.

SU5402 is purely manufactured for laboratories and not licensed for therapeutic use.

But scientists hope the research, published in the latest online issue of the journal Nature, will lead to future treatments.

Senior researcher Dr Albert Basson, from King's College London, said: "Preventing or reversing muscle wasting in old age in humans is still a way off, but this study has for the first time revealed a process which could be responsible for age-related muscle wasting, which is extremely exciting.

"The finding opens up the possibility that one day we could develop treatments to make old muscles young again. If we could do this, we may be able to enable people to live more mobile, independent lives as they age."

Co-author Dr Andrew Black, from Massachusetts General Hospital in the US, said: "Just as it is important for athletes to build recovery time into their training schedules, stem cells also need time to recuperate, but we found that aged stem cells recuperate less often.

"We were surprised to find that the events prior to muscle regeneration had a major influence on regenerative potential. That makes sense to us as humans, in terms of the need to sleep and to eat a healthy diet, but that the need to rest also plays out at the level of stem cells is quite remarkable."

The scientists still do not know why levels of FGF2 increase with age, causing excessive activation of stem cells.

"The next step is to analyse old muscle in humans to see if the same mechanism could be responsible for stem cell depletion in human muscle fibres, leading to loss of mass and wastage," said team member Kieran Jones, from King's College.

Dr Basson said that, although the drug used in the research could not be given to patients, other FGF-2 inhibitors were already being tested as potential cancer treatments.

"There are a number of newer generation drugs that target the same pathway that are in clinical trials for cancers," he said.

"There are these drugs around, but in a tumour context."

Why too much activation of the stem cells led to their depletion was still a mystery, he added.

A likely reason was that the stem cells were programmed to divide only a limited number of times before dying.

Dr Basson did not want to speculate how far away muscle-restoring treatments might be.

"It could be five years, 10 years, it's impossible to say," he said.

He added that the same process might cause tissues other than muscle to degenerate.

"The mechanism we're looking at here might be very muscle- specific, or possibly a similar thing might be happening in the brain, we don't know," said Dr Basson.