Decline in recovery regarding recovery from age-related muscle injury can be traced to a protein that suppresses the particular ability of muscle stem cells to build new muscle, according to the work of a team of current and former Carnegie-led biologists. Jan and posted on Metabolism of nature.
Skeletal muscle has a tremendous capacity to make new muscle from specialized muscle stem cells. These "empty" cells are not only good for building muscle, but also for creating more of them, a process called self-renewal. But their incredible abilities diminish with age, resulting in less muscle regeneration from muscle trauma.
The research team – including Carnegie Lianzi Lee, Michelle Rosso, Sibio Hue, Xiabin Hengeng and Frederick Tan, as well as Christoph Lepper formerly of Carnegie now at Ohio State University – have discovered that a protein called GAS1 is to blame.
"Coded by the specific growth arrest gene, the GAS1 protein lives up to its name, accelerating the functional decline of muscle stem cells," explained lead author Lee.
The protein is found in only a small number of young stem cells, but is present in all adult muscle stem cells, they found. Mixing with muscle stem cells to express GAS1 in the whole young stem cell population resulted in reduced regeneration. In contrast, removing GAS1 from the old muscle stem cells rejuvenated them in a youthful state that supported robust regeneration.
They also discovered that GAS1 inhibits another protein, a cell surface receptor called RET, which they have shown is necessary for the recovery of muscle stem cells. The more protein GAS1 has, the greater the function of RET.
Inhibition of RET by GAS1 can be altered by a third protein called GDNF, which binds to and activates RET. Indeed, when the researchers injected GDNF directly into the mouse muscle at age, it returned to stem cell function and muscle regeneration.
"As the population ages, problems such as muscle deterioration are increasingly a social challenge," Jan said. "Our work may reveal a potential pathway for therapeutic targeting to combat muscle degeneration in the elderly."
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