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Boost in mystery muscle creates endurance mice

January 2, 2007 By Helen Pearson This article courtesy of Nature News.

Rare muscle fibres could improve sporting prowess.

A genetic tweak has converted mice into endurance runners by enriching a little-known form of muscle fibre. The discovery could help boost sporting abilities, or reveal ways to slow muscle wasting.

Human muscles are made of four main types of fibre, including two 'slow-twitch' varieties and one 'fast-twitch' muscle type that are suited to endurance and sprint activities respectively. Little has been known about the fourth type, called IIX fibre, because it is scattered throughout different muscles.

Now a Boston team has hit upon a genetic switch that converts almost all mouse muscle fibres into type IIX. The result is startling. "Damn, they're good athletes," says Bruce Spiegelman of Harvard Medical School, who led the team. The mice were able to run on a mouse treadmill for 25% longer than normal before reaching exhaustion.

The discovery hints that the elusive type IIX muscle fibres are an underappreciated contributor to athletic ability. It is possible, for example, that world-class athletes are naturally endowed with more of these fibres than the average person or that hard training generates more of them.

If so, notes study researcher Zoltan Arany, also of Harvard Medical School, future athletes might try to take advantage of the discovery. It is possible, he predicts, that "someday we'll have drugs that switch on the production of these fibres and they'll be abused by sportsmen".

Previous work has shown that boosting some muscle fibre types can help to slow muscle decay. So Arany notes that further studies into these fibres might one day help people who suffer from amyotrophic lateral sclerosis or other conditions that waste away muscles.


The different muscle fibre types have qualities that lend themselves to different types of activity.

Slow-twitch fibres types I and IIA are packed with power-generating machines called mitochondria and are called into use mainly for continuous, endurance exercises such as walking that use up lots of oxygen. The soleus muscle in the calf, for example, is full of these fibres.

Fast-twitch, or type IIB, fibres contract in shorter, sharper bursts, and tend to operate without oxygen. They are generally called upon for spurts of quick, powerful activity. The quadriceps, vital in sprinting, are rich in these fibres.

Type IIX fibres are somewhere in between: they have lots of mitochondria but also contract quickly. One idea is that fibres go through a stage of being IIX during a conversion from fast-twitch to slow-twitch types, and that this might happen during certain forms of training. But their function is not known for certain.

Designed to run

Four years ago, Spiegelman's team found that firing up a gene called PGC-1 converted muscles that were a mix of fibre types into mainly slow-twitch fibres1.

Their new work, published in Cell Metabolism2, uses genetic engineering to switch on a sibling gene called PGC- in mice muscles. This transformed muscles that normally contain 15-20% type IIX fibres into ones with nearly 100%.

The two genes are thought to help switch on entire cascades of genes that convert one muscle fibre type to another.

Such studies allow researchers to examine in more detail how different muscle fibres behave, and how they affect physical ability.

Scientists don't know exactly what enables particular people to succeed at marathons or ultra-endurance events such as ultramarathons (see ' Physiology: Freaks of nature?'). Spiegelman says that he now wants to explore whether such athletes have a different form of PGC- or more IIX muscle fibres.

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  1. Lin J., et al. Nature, 418. 797 - 801 (2002).
  2. Arany Z., et al. Cell Metabolism, 5. 35 - 46 (2007).


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