The discovery of the long-sought switch, a molecule called PGC-1, might some day enable physicians to give weakened patients a drug to build up muscular endurance without exercise, say the researchers. Normally, the only way to achieve this muscular reprogramming is through long, demanding training regimens.

Published in the Aug. 15 issue of the journal Nature, the findings describe the pivotal role of PGC-1 in transforming "fast twitch" fibers (Type II) to "slow twitch" fibers (Type I). "Fast twitch" fibers create the bulkier, strong but quickly fatigued muscles of weightlifters or sprinters. Most muscles contain a combination of the two fibers.

"PGC-1 appears to be the switch, or a major component of it, that enables your body's muscles to adjust to the demands being put on them," explains Dana-Farber's Bruce M. Spiegelman, PhD, a cell biologist and the study's senior author. "Understanding how this system works could make it possible to develop a drug to manipulate this system."

The research team included investigators from Dana-Farber, Beth Israel Deaconess Medical Center, Boston, and the University of Texas Southwestern Medical Center, Dallas.

Spiegelman's laboratory had previously shown that PGC-1, a molecule known as a "transcriptional co-activator," acts as a switch in the liver to regulate the manufacture of glucose, which fuels cells.

In the muscle research, PGC-1 was found to have a somewhat similar role: it triggers the development of cellular power plants called mitochondria that give slow-twitch fibers their extraordinary endurance. At the same time, the process turned on by PGC-1 produces proteins such as myoglobin tha
'"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
14-Aug-2002