Genetically Engineering Endurance: The Future of the Olympics?

SAN FRANCISCO -- Forget Drug Testing, Scientists Publish Papers in PLoS Biology that Predict Genetically Engineered Enhancements in Athletes

Scholarly journal PLoS Biology today published research by two groups that have genetically engineered different pathways to change mice from Sunday morning joggers to Olympic marathoners - "Marathon Mice." Randall Johnson and colleagues have discovered a protein found in skeletal muscle that profoundly influences muscle endurance, while Ronald Evans and colleagues have genetically engineered muscle phenotype in a manner that dramatically improves endurance and running performance.

Skeletal muscles come in two basic types: type I, or slow twitch, and type II, or fast twitch. Slow-twitch fibers rely on oxidative (aerobic) metabolism and have abundant mitochondria that generate the long-lasting supplies of ATP, needed for long distance. Fast-twitch fibers, which produce ATP through anaerobic glycolysis, generate rapid, powerful contractions but fatigue easily. Top-flight sprinters have up to 80% type II fibers while long-distance runners have up to 90% type I fibers. Couch potatoes have about the same percentage of both.

Endurance training can enhance the metabolic performance of muscle types probably by inducing conversion between fiber types, which is mediated by changes in gene expression. Evans and colleagues suspected that a nuclear receptor called PPAR-delta - a major regulator of fat burning in fat tissue that is also prevalent in skeletal muscle - might be involved and genetically engineered mice to express an activated form of the PPAR-delta protein in skeletal muscle. The transgenic mice showed much higher levels of the protein, and much redder muscles, than their normal littermates. This suggests that muscle fibers can be transformed into type I endurance fibers by simply activating the endogenous PPAR-delta pathway. Remarkably, the transgenic ran about an hour longer than controls, showing dramatic improvement in both running time and distance-increases of 67% and 92%, respectively. The genetically engineered conversion of type I muscle fibers not only enhance physical performance but could presumably protect against obesity.

The finding that endurance and running capacity can be genetically manipulated suggests that muscle tissue is far more adaptable than previously thought. Maybe Olympiads can be made after all-but don't give up on training just yet. Will drug testing become obsolete? How will Olympic officials test for genetically engineered endurance? These are the athletic questions of the future.

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Citation: Mason S, et al. (2004) Loss of Skeletal Muscle HIF-1a Results in Altered Exercise Endurance. PLoS Biol 2 (10): e288.

The published article will be accessible to your readers at: http://plosbiology.org/plosonline/?request=get-document&doi=10.1371/ journal.pbio.0020288

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Press-only preview of the article: http://www.plos.org/downloads/plbi-02-10-johnson.pdf

CONTACT:
    Randall S. Johnson
    University of California, San Diego
    9500 Gilman Drive, MC-0377
    La Jolla, CA USA
    [phone]
    [phone] (fax)
    [e-mail]

Citation: Wang Y, et al. (2004) Regulation of Muscle Fiber Type and Running Endurance by PPAR-delta PLoS Biol 2 (10): e294.

The published article will be accessible to your readers at: http://plosbiology.org/plosonline/?request=get-document&doi=10.1371/ journal.pbio.0020294

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Press-only preview of the article: http://www.plos.org/downloads/plbi-02-10-evans.pdf

CONTACT:
    Ronald Evans
    Howard Hughes Medical Institute
    The Salk Institute for Biological Studies
    10010 N. Torrey Pines Rd.
    San Diego, CA USA
    [phone] x1302
    [phone] (fax)
    [e-mail]