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Age-related muscle loss linked to protein interplay, says Stanford researcher

STANFORD, Calif. - Any older athlete can attest that aging muscles don't heal as fast as youthful ones. Now researchers at Stanford University School of Medicine have found a molecular link between older muscles and slow healing. This work could lead to ways of preventing atrophy from immobilization, space flight or simply due to aging.

"What you really want to do is maintain the youthfulness of the regeneration pathway," said Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences and an investigator at the Veterans Affairs Palo Alto Health Care System. The work will be published in the Nov. 28 issue of Science.

Rando and postdoctoral scholar Irina Conboy, PhD, focused their attention on a group of cells called satellite cells, which dot the outside of muscle fibers. These cells come to the rescue of damaged muscles, dividing to form new muscle tissue and generating new satellite cells for future repairs.

In previous work, Rando found that satellite cells spring into action when a protein on the cell surface called Notch becomes activated, much like flicking the cell's molecular "on" switch. What flips the switch is another protein called Delta, which is made on nearby cells in injured muscle. This same combination of Delta and Notch also plays a role in guiding cells through embryonic development.

Having found this pathway, Rando and Conboy wondered whether slow healing in older muscles resulted from problems with signaling between Delta and Notch - failing either to make enough Delta or to respond to the Delta signal.

In their initial experiments, Rando and Conboy found that young, middle-aged and older mice all had the same number of satellite cells in their muscles and that these cells contained equivalent amounts of Notch.

"It doesn't seem as if there's anything wrong with the satellite cells or Notch in aged muscle," Rando said. That left Delta as the suspect molecule.

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Contact: Amy Adams
650-723-3900
Stanford University Medical Center
27-Nov-2003


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