Keeping it up (Image: Cultura/plainpicture)

IT COULD be the biggest killer you’ve never heard of: the weakening and loss of muscle that happens as we get older.

Muscle loss is no longer seen as just a side effect of disease and frailty – it’s also a prime cause. As well as contributing to falls, muscle loss has serious knock-on effects on metabolism (see “Life-saving muscle”). In future, muscle-boosting drugs could aid those unable to maintain muscle mass through exercise such as weight training. Although researchers stress this isn’t about bodybuilding, but keeping muscles in your limbs at a healthy level.

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Muscle loss, also known as sarcopenia, is increasingly being seen as an important facet of ageing, according to several speakers at a conference on longevity drugs held in Basel, Switzerland, last month. “Treatments will eventually get into the market,” said Dan Perry of the patient lobby group Alliance for Aging Research.


However, the mechanisms behind muscle ageing are still poorly understood – although new research suggests it involves damage from free radicals.

Mice that have been genetically modified to produce fewer free radicals in their mitochondria are known to live about 20 per cent longer than normal mice. So a team led by Andrew Marks at Columbia University in New York investigated how this affected the ageing of their muscle tissue.

They found that a key player is calcium, the release of which triggers our muscles to contract. The molecule responsible for this release – ryanodine receptor 1 – is damaged by free radicals, and as the rodents age, calcium begins to leak out when it shouldn’t, weakening muscle fibres.

The modified mice experienced less free radical damage to the ryanodine receptor 1. They also had stronger muscles, and, in old age, chose to run on their exercise wheels more than unmodified mice – by about an extra kilometre a day (PNAS, doi.org/v64).

“It helps point to the role that mitochondria play in the muscle ageing process,” says Daniel Moore of the University of Toronto, Canada.

Marks has founded a firm called Armgo to develop several compounds aimed at preventing calcium leakage, which are in early-stage clinical trials.

“People think of muscle as the body’s mover, but it’s really a huge metabolic organ”

Other drugs are in development that combat sarcopenia in different ways. Muscle fibres are in a constant state of turnover, being simultaneously broken down and regrown, so any compound that tips the balance towards growth could help build muscle mass.

One class of drug includes the compound bimagrumab, which works by blocking a signalling pathway targeted by an inhibitor of muscle growth called myostatin. Others work by mimicking the effects of testosterone in a safer way than existing steroid drugs.

“There’s a lot of interest in trying to come up with something for sarcopenia because at the moment there’s no treatment,” says Marks.

Indeed, it’s only within the last six months that US researchers have even agreed on how to define the condition – essential before a drug treatment can be approved. The US National Institutes of Health published its results in May.

“We have come a long way in how to approach this,” says Jack Guralnik of the University of Maryland, who was involved in the defining process.

In the meantime, there is already a natural way to boost muscle: exercise. “The mitochondrial function of lifelong exercisers is like that of someone half their age,” says Moore. “One of the best anti-ageing pills is to stay active.”

Life-saving muscle While a six-pack is seen as the preserve of body builders or athletes, muscularity should be a concern for anyone who plans on living a long time (see main story). As we age, our muscle fibres start to perform less well and we lose muscle mass – with serious consequences. Older people with weaker grip strength, for instance, are more likely to die in the next few years – even when compared with people apparently in similar health (BMJ, doi.org/dzn7wm). One explanation is that as people’s strength decreases they are more likely to fall, and if an older person breaks a bone and is bed-ridden for several weeks they lose further muscle and bone mass. This may help to explain why 1 in 3 people who fracture their hip in the UK die within 12 months, according to National Health Service figures. “It’s a vicious circle,” says Avan Aihie Sayer at the University of Southampton, UK. What’s more, muscle is the only place the body can store amino acids – the building blocks of proteins – so when someone with little muscle becomes ill they have few reserves to call on. Healthy muscle tissue is also a major consumer of glucose, so lack of muscle means the body can’t cope well with the surge of blood glucose after meals, which slowly nudges people down the road to diabetes. “People think of muscle as the body’s mover, but it’s really a huge metabolic organ,” says Daniel Moore of the University of Toronto, Canada.

This article appeared in print under the headline “Beefing up can keep you healthy”