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A drug compound appears to make muscle stem cells in aged mice act like their former selves. Amy Wagers of the Joslin Diabetes Center in Boston, Mass, has for some time been able to show that parabiosis, in which the circulatory systems of young mice are spliced with those of older mice, gives muscle stem cells in older mice the regenerative capabilities of the younger mice. But identifying what, among the countless components of the youthful blood, could possibly be changing the behaviours of the stem cells remains challenging. Now, she shows that a drug can mimic the effects of parabiosis on aging stem cells offering hope that therapies may one day help older people after muscle injury. She presented her results today at the 50th annual meeting of the American Society for Cell Biology in Philadelphia.
Wagers had to retract a paper on this area of her research earlier this year due to “concerns about the data,” but she has said that the rationale behind the research remains valid. She has developed a way of screening chemicals that would promote regeneration in muscle stem cells from older mice the same way that parabiosis between young and old mice does. Working with a chemical library from Glaxo Smith Klein she identified a compound, A25, that selectively blocks a protein involved in TGFBeta signalling. To test it, they injured mouse muscle with dry ice and administered the drug. They then harvested the muscle and looked to see how the drug affected the cells’ regenerative abilities.
The drug had no effect on the tissue of young mice, but in older mouse tissue, she says, “the inhibitor had a profound effect,” giving them regenerative abilities similar to that of the young mice. Because it would target TGFBeta signalling throughout the body, the drug would probably not be useful as a therapeutic for aging in humans, Wagers says. But the results do show that “extrinsic signals can enhance the activity of muscle stem cells.” Further researcher could identify appropriate drugs to combat muscle wasting or help older individuals heal after injury.
Wagers is also studying how calorie restriction and chemical signals associated with low calorie diets increase the number of muscle stem cells and help improve the abilities of transplanted stem cells to engraft into muscle tissue.
Image: “Lucky” by Icky Pic/Jimmy Changa