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Decoding Muscle Stem Cell Development
Date:5/12/2008

Nutrient restriction triggers pathway involved with life span, study finds

MONDAY, May 12 (HealthDay News) -- Muscle stem cells can't grow into mature muscle cells if there aren't enough nutrients, according to a study that offers new insight into how developing muscle cells sense and respond to nutrient levels.

The research, part of ongoing investigations into the effects of caloric restriction on physiology and aging, may help in the development of new treatments for muscle wasting.

In this study, National Institutes of Health researchers examined how the availability of glucose affects the ability of muscle stem cells (myoblasts) to develop into mature skeletal muscle fibers.

According to a news release about the study, the researchers "found that glucose restriction (GR) impaired differentiation of skeletal myoblasts and activated AMP-activated protein kinase (AMPK). These results define a pathway in which activation of AMPK in response to low glucose levels stimulates expression of the NAD+ biosynthetic enzyme Nampt. NAD+ is a known co-factor of SIRT1, which plays an important role in numerous physiological processes, including differentiation of skeletal muscle cells, and has been implicated in regulation of life span and aging. Importantly, inhibition of AMPK, Nampt or SIRT1 resulted in skeletal muscle cells that were oblivious to a nutrient-poor environment and were able to differentiate under conditions that otherwise would not be suitable."

The researchers said their findings, published in the May issue of Developmental Cell, show that a specific pathway controls muscle cell differentiation in response to low nutrient levels.

"We speculate that, functioning as a cellular checkpoint, the AMPK-Nampt-SIRT1 pathway may be activated by reduced nutrient availability to prevent cells from undertaking energy-demanding processes -- such as cell differentiation -- during calorie-unfavora
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