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Scientists discover clues to what makes human muscle age
Date:9/29/2009

young muscle, in terms of tissue maintenance and functionality, whereas old muscle began to atrophy and manifest signs of rapid tissue deterioration," said Carlson, the study's first author and a UC Berkeley post-doctoral scholar funded in part by CIRM. "The old muscle also didn't recover as well with exercise. This emphasizes the importance of older populations staying active because the evidence is that for their muscle, long periods of disuse may irrevocably worsen the stem cells' regenerative environment."

At the same time, the researchers warned that in the elderly, too rigorous an exercise program after immobility may also cause replacement of functional muscle by scarring and inflammation. "It's like a Catch-22," said Conboy.

The researchers further examined the response of the human muscle to biochemical signals. They learned from previous studies that adult muscle stem cells have a receptor called Notch, which triggers growth when activated. Those stem cells also have a receptor for the protein TGF-beta that, when excessively activated, sets off a chain reaction that ultimately inhibits a cell's ability to divide.

The researchers said that aging in mice is associated in part with the progressive decline of Notch and increased levels of TGF-beta, ultimately blocking the stem cells' capacity to effectively rebuild the body.

This study revealed that the same pathways are at play in human muscle, but also showed for the first time that mitogen-activated protein (MAP) kinase was an important positive regulator of Notch activity essential for human muscle repair, and that it was rendered inactive in old tissue. MAP kinase (MAPK) is familiar to developmental biologists since it is an important enzyme for organ formation in such diverse species as nematodes, fruit flies and mice.

For old human muscle, MAPK levels are low, so the Notch pathway is not activated and the stem cells no longer perform their muscle regeneration
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Contact: Sarah Yang
scyang@berkeley.edu
510-643-7741
University of California - Berkeley
Source:Eurekalert  

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