Study discovers protein that causes age-related muscle degeneration

As per a study conducted by former Carnegie biologists led by Chen-Ming Fan suggests that an age-related decline in recovery after muscle injury can be caused by a protein that supresses the ability of muscle stem cells to make new muscles. Skeletal muscles have a tremendous capacity to create new muscles from special muscle stem cells. The “blank” cells are not just capable of making muscles, but also at self-renewal, wherein they can create more of themselves. However, this excellent capability is lost with age, which results in weaker muscle regeneration following muscle trauma. The team’s findings have been published in the journal Nature Metabolism.

The team, which included Carnegie’s Frederick Tan, Michelle Rozo, Liangji Li, Sibiao Yue, and Xiaobin Zheng, along with Christoph Lepper, formerly of Carnegie now at the Ohio State University, discovered that a protein, known as “GAS1,” is the reason behind the age-related decline in muscle regeneration capacity. Li explains that the GAS1 protein, encoded by the growth-arrest specific gene, can expedite the functional decline of muscle stem cells. The protein is present in a small number of young muscle stem cells but is present in all aged muscle stem cells. Modifying the muscle stem cells to express GAS1 in the entire young stem cell population led to diminished regeneration. Conversely, removing GAS1 from aged muscle stem cells restored them to a youthful state that facilitates stable regeneration. They also found that the GAS1 blocks another protein, a cell-surface receptor known as RET, which they believe is necessary for muscle stem cell renewal. The higher the concentration of GAS1 protein, the lower is the function of RET.

GAS1’s ability to inhibit RET could be reversed with the help of a third protein known as GDNF, which attaches to and triggers RET. During the study, when the researchers directly injected GDNF into the muscles of aged mice, they observed that muscle stem cell functions and muscle regeneration were restored. Tan says that the study could reveal a potential pathway to target and combat muscle degeneration in the geriatric population therapeutically.


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