Researchers at the Perelman School of Medicine at the University of Pennsylvania have identified a gene for endurance, or more precisely, a negative regulator of it. Not having the gene relates to greater endurance in the knockout mice that were studied. The investigators also showed that the gene is linked to Olympic-level athletes in endurance sports such as swimming compared to athletes in sprint sports such as the 100-meter dash. The study appears online this week in the Journal of Clinical Investigation. The work has implications for improving muscle performance in disease states including metabolic disorders, obesity, and aging.

"We have shown that mice lacking the gene run six times longer than control mice and that the fatigable muscles of the mouse -- the fast muscle in the front of the leg -- have been reprogrammed and are now fatigue-resistant," explains senior author Tejvir S. Khurana, MD, PhD, professor of Physiology and member of the Pennsylvania Muscle Institute. "This has wide ramifications for various aspects of muscle biology ranging from athletics to treating muscle and metabolic diseases."

The gene codes for a protein called Interleukin-15 receptor-alpha (IL-15R-alpha), which acts alone or in conjunction with the IL-15 protein. IL-15R-alpha is important in the immune response, but it also has other functions. IL-15 and IL-15R-alpha have been implicated in muscle physiology, but the exact role in muscle function has not been defined.

"We found a previously unrecognized role for IL-15R-alpha in defining muscle function, and manipulation of this gene has the potential to improve muscle performance in disease states including metabolic disorders, obesity, and aging." says lead author Emidio E. Pistilli, PhD, who was a postdoctoral researcher at Penn and is now an assistant professor in the Division of Exercise Physiology at the West Virginia School of Medicine.

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