"Long before it's in the papers"
December 07, 2012

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Newfound protein linked to big, strong muscles

Dec. 7, 2012
Courtesy of Dana Farber Cancer Institute
and World Science staff

Sci­en­tists have linked a pre­vi­ously un­known pro­tein to big­ger, stronger mus­cles fol­low­ing re­sist­ance ex­er­cise, such as weigh­lift­ing. 

Mice en­gi­neered to have more of the mol­e­cule gained mus­cle mass and strength, and when af­flicted by can­cer were much less af­fect­ed by ca­chex­ia, a loss of mus­cle com­mon in can­cer pa­tients, the re­search­ers said.

“If you could find a way to el­e­vate lev­els of this pro­tein, that would be very ex­cit­ing,” said Jor­ge Ruas of the Dana-Farber Can­cer In­sti­tute in Bos­ton, co-au­thor of a re­port on the work in the Dec. 7 is­sue of the jour­nal Cell. “You might be able to re­duce mus­cle wast­ing in pa­tients in in­ten­sive care un­its whose mus­cles at­ro­phy be­cause of pro­longed bed rest.” Peo­ple with mus­cu­lar dys­tro­phy and aging-related mus­cle loss might al­so ben­e­fit, he added.

The pro­tein, called PGC-1 alpha-4, was found in skele­tal mus­cle in mice and hu­mans, said Bruce Spiegel­man of the in­sti­tute, the re­port's sen­ior au­thor. He added that re­sist­ance ex­er­cise, such as weight lift­ing, boosts PGC-1 alpha-4, trig­ger­ing bio­chem­i­cal changes.

The pro­tein is an iso­form, or slight var­i­ant, of PGC-1 al­pha—an im­por­tant reg­u­la­tor of body me­tab­o­lism turned on by forms of ex­er­cise, such as run­ning, that in­crease mus­cle en­dur­ance rath­er than size. “It's pret­ty amaz­ing that two pro­teins made by a sin­gle gene reg­u­late the ef­fects of both types of ex­er­cise,” said Spiegel­man.

The re­search­ers found the new pro­tein con­trols the ac­ti­vity of two pre­vi­ously known mo­lec­u­lar mech­a­nisms in­volved in mus­cle growth: a rise in PGC-1 alpha-4 with ex­er­cise in­creases ac­ti­vity of a pro­tein called insulin-like growth fac­tor 1, which fa­cil­i­tates mus­cle growth, and al­so re­presses an­oth­er pro­tein, myo­statin, that puts brakes on mus­cle growth.

The in­ves­ti­ga­tors used vi­rus­es to sneak PGC-1 alpha-4 in­to the leg mus­cle of mice and found that with­in days their mus­cle fibers were 60 per­cent big­ger. They al­so en­gi­neered mice to have more PGC-1 alpha-4 in their mus­cles than nor­mal mice who were­n't ex­er­cis­ing. The treated mice were found to be 20 per­cent stronger, more fatigue-resistant and lean­er than their nor­mal coun­ter­parts.

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Scientists have linked a previously unknown protein to bigger, stronger muscles following resistance exercise, such as weighlifting. Mice engineered to have more of the molecule gained muscle mass and strength, and when afflicted by cancer were much less affected by cachexia, a loss of muscle common in cancer patients, the researchers said. “If you could find a way to elevate levels of this protein, that would be very exciting,“ said report Jorge Ruas of the Dana-Farber Cancer Institute in Boston, co-author of a report on the work in the Dec. 7 issue of the journal Cell. “You might be able to reduce muscle wasting in patients in intensive care units whose muscles atrophy because of prolonged bed rest.“ People with muscular dystrophy and aging-related muscle loss might also benefit, he added. The protein, called PGC-1 alpha-4, was found in skeletal muscle in mice and humans, said Bruce Spiegelman of the institute, the report's senior author. He added that resistance exercise, such as weight lifting, boosts PGC-1 alpha-4, triggering biochemical changes. The protein is an isoform, or slight variant, of PGC-1 alpha—an important regulator of body metabolism turned on by forms of exercise, such as running, that increase muscle endurance rather than size. “It's pretty amazing that two proteins made by a single gene regulate the effects of both types of exercise,“ said Spiegelman. The researchers found the new protein controls the activity of two previously known molecular mechanisms involved in muscle growth: a rise in PGC-1 alpha-4 with exercise increases activity of a protein called insulin-like growth factor 1, which facilitates muscle growth, and also represses another protein, myostatin, that puts brakes on muscle growth. The investigators used viruses to sneak PGC-1 alpha-4 into the leg muscle of mice and found that within days their muscle fibers were 60 percent bigger. They also engineered mice to have more PGC-1 alpha-4 in their muscles than normal mice who weren't exercising. The treated mice were found to be 20 percent stronger, more fatigue-resistant and leaner than their normal counterparts.