Stanford researchers find culprit in aging muscles that h...( cellular turnover. Rando and his ...),Health

Rando and his colleagues made the discovery while studying the effect of environment on muscle stem cell activity in mice. Rando had already discovered that old muscle stem cells, if placed in a youthful environment, had just as great a capacity for repairing acutely damaged tissue as do young cells.

It was while the researchers were testing the opposite situation - how the repair capabilities of young muscle stem cells were affected by being placed in an aged environment - that the Wnt pathway came to light. The work was done with live mice whose circulatory systems were joined, and in lab dishes with young cells immersed in serum from old blood.

As expected, the young muscle stem cells were influenced negatively by the aged environment, repairing damaged muscle tissue just as slowly and poorly as old stem cells in the same surroundings. This confirmed their earlier research showing that the ability of muscle stem cells to regenerate tissue depends on the age of the cells' environment (including the age of the blood supplying the tissue), not the age of the stem cell.

Although Rando's research focused on the repair of acute trauma to muscles, he suspects that the same sort of problem arises on a lesser scale in repairing damage that results from the normal wear and tear of aging.

Rando also found that the misdirected stem cells - the ones that failed to generate new muscle cells in the old environment - were instead differentiating into scar-tissue-producing cells called fibroblasts. The stem cells weren't just failing to respond to the garbled instructions, they were actually giving rise to daughter cells that turned into the wrong thing. The consequence of muscle stem cells producing fewer muscle cells (myoblasts) and more fibroblasts is that the healing muscle had more scar tissue, also known as fibrosis.

"That says something about how cells decide who they're going to be. Even if th
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Contact: Louis Bergeron
louisb3@stanford.edu
650-723-3900
Stanford University Medical Center
9-Aug-2007