A One-Two Gene Knockout Makes Mice Stronger and Faster

Swiss scientists have discovered that knocking out the nuclear receptor corepressor 1 (NCoR1) gene in the muscles of mice allow the animals to run farther, and faster. Knocking out the same gene in fat cells eliminated the problem of diabetes in the mice. And those are only two tissues, of the many types of tissues in a mouse's body. I wonder if knocking out the NCoR1 gene in human muscles would create a super athlete?

Knocking out a particular gene in muscle lets mice run twice as far as normal. Knocking out the same gene in fat cells allows the animals to put on weight without developing type-2 diabetes.

The discoveries could lead to new treatments for diabetes or for invigorating muscles in elderly people and in those with wasting diseases, say Johan Auwerx of the Federal Polytechnic School of Lausanne, Switzerland, and colleagues.

...Auwerx and his colleagues used a targeted virus to knock out the gene that makes a protein called nuclear receptor corepressor 1 (NCoR1) in the muscle of mice. Without NCoR1, mitochondria, which power cells, keep working at full speed. "Effectively, the mice go further, faster, on the same amount of gas," says Auwerx.

"The treated mice ran an average of 1600 metres in 2 hours, compared with 800 metres for untreated mice," he says.

...Auwerx warns athletes not to try to grow their muscles and stamina illicitly by somehow targeting the NCoR1 protein, however.

"We only know what happens if it's knocked out either in fat or muscle, and it could have serious side effects on other organs," he says. Also, he points out that without NCoR1, all fetuses perish, so it plays a vital but undiscovered role in fetal development. _NewScientist

Right. As if Auwerx' warnings would have any effect on a determined athlete's plans. And there are likely several other ways for athletes to tweak their muscles' genes, to gain an advantage.

One gene, for example, called MYH16, contributes to the development of large jaw muscles in other apes. In humans, MYH16 has been deactivated. (Puny jaws have marked our lineage for as least 2 million years.) Many people have also lost another muscle-related gene called ACTN3. People with two working versions of this gene are overrepresented among elite sprinters while those with the nonworking version are overrepresented among endurance runners. _Slate

More muscle boosting genes:

CNTF 1357 G → A polymorphism and the muscle strength response to resistance training Jnl Appl Physio 2009

Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates Sci Transl Med 2009

Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors PNAS 2008

Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging PNAS 2009

Genetically boosted athletes are inevitable, once stealth techniques of controlling gene expression and transfer are developed. But that also means that viable means of strengthening the muscles, bones, and other tissues that normally weaken with ageing, will also be within reach. So it's best not to complain too loudly about the athletes who tweak themselves for advantage, so long as the rest of us can win in the game of life.

Abstract from Cell:

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/δ, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function. _Cell