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Science 21 January 2005:
Vol. 307. no. 5708, pp. 418 - 420
DOI: 10.1126/science.1108177
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Reports

Cardiovascular Risk Factors Emerge After Artificial Selection for Low Aerobic Capacity

Ulrik Wisløff,1,2*{dagger} Sonia M. Najjar,3* Øyvind Ellingsen,1,2 Per Magnus Haram,1 Steven Swoap,4 Qusai Al-Share,3 Mats Fernström,3 Khadijeh Rezaei,3 Sang Jun Lee,3 Lauren Gerard Koch,5 Steven L. Britton5

In humans, the strong statistical association between fitness and survival suggests a link between impaired oxygen metabolism and disease. We hypothesized that artificial selection of rats based on low and high intrinsic exercise capacity would yield models that also contrast for disease risk. After 11 generations, rats with low aerobic capacity scored high on cardiovascular risk factors that constitute the metabolic syndrome. The decrease in aerobic capacity was associated with decreases in the amounts of transcription factors required for mitochondrial biogenesis and in the amounts of oxidative enzymes in skeletal muscle. Impairment of mitochondrial function may link reduced fitness to cardiovascular and metabolic disease.

1 Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Olav Kyrres gt. 3, 7489 Trondheim, Norway.
2 Department of Cardiology, St. Olavs Hospital, 7006 Trondheim, Norway.
3 Department of Pharmacology, Cardiovascular Biology, and Metabolic Diseases, Medical College of Ohio, 3035 Arlington Avenue, Toledo, OH 43614–5804, USA.
4 Department of Biology, Williams College, Williamstown, MA 01267, USA.
5 Department of Physical Medicine and Rehabilitation, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109–0718, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ulrik.wisloff{at}medisin.ntnu.no

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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