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Researchers Switch Off Gene in Mice to Switch on Endurance

80beatsBy Joseph CastroJuly 21, 2011 2:00 AM


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What’s the News: By knocking out a single gene, scientists at the University of Pennsylvania have significantly increased the physical endurance of lab mice

, as explained in their recent paper in the Journal of Clinical Investigation. The researchers also found that certain variants of the same gene may be linked to greater endurance in humans. How the Heck:

  • Past in vitro studies showed that a gene called IL-15Rα is involved in controlling muscle contractions, which play a role in both muscle strength and endurance. But the gene has never been studied in a living animal, so physiologist Tejvir Khurana and his research team decided to engineer lab mice that lack IL-15Rα.

  • They noticed that at night the altered mice ran six times farther than normal mice. When the team dissected the engineered mice, they found that their muscles had more fibers than normal mice, as well as a higher number of mitochondria, the power plants of cells. Moreover, the researchers saw that muscle contractions in the engineered mice lasted longer than normal. These observations all pointed to one obvious conclusion: the muscles took longer to tire and burn through their energy stores.

  • The lack of the gene caused one type of muscle fiber to turn into another, the researchers explained to Science NOW. In the mice’s legs, fast-twitch fibers, which contract quickly and powerfully, converted into the more fatigue-resistant slow-twitch fibers.

  • The team then investigated how the human IL-15Rα gene affects human endurance by studying genetic samples of Olympic and world-class athletes. They found that certain variants—or alleles—of the gene were more common in endurance athletes like long-distance cyclists than in sprinters.

What’s the Context:

  • Scientists have long known that endurance training alters muscles fibers, though this new study pinpoints a specific gene seemingly linked to this change.

  • In 2004, biologist Ronald Evans and his research team at the Salk Institute found that the regulation of a protein called PPARδ, involved in the formation of slow-twitch muscles fibers, can also boost endurance in mice. Khurana and his team aren’t sure what the connection is between IL-15Rα and PPARδ, according to Science NOW.

  • A few years ago, the Salk Institute created a drug, GW1516, that activates PPARδ, but it only works in mice when exercise is thrown into the mix. AICAR, another drug the institute developed, increased endurance in mice without requiring exercise by activating a gene called AMPK.

Not So Fast: While it seems clear that knocking out the IL-15Rα can improve endurance, the research doesn’t explain why the engineered mice voluntarily ran more than the normal mice. There may be an undiscovered psychological component at work, Evans told Science NOW

. The Future Holds: The researchers suggest that scientists could someday develop drugs to block IL-15Rα to enhance endurance. Specifically, this would be useful for diabetics and the elderly, whose health is often negatively impacted by fatigue. (via Science NOW


Image: Wikimedia Commons/Rama

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