One of the most obvious effects of aging is loss of muscle mass – scientists at the Salk Institute in California, US, may have found a way to overcome this problem and enable more effective tissue regeneration in aging adults as well as athletes.

Using a combination of molecular compounds, the scientists showed that regeneration of muscle cells in mice was possible by activating the precursors of muscle cells, called myogenic progenitors. These compounds, often called Yamanaka factors, after the Japanese scientist who discovered them, are a combination of proteins (called transcription factors) that control how DNA is copied for translation into other proteins. In stem cell research, Yamanaka factors are used to convert specialized cells into pluripotent stem cells, which means they have the ability to become many different types of cells.

“Loss of these progenitors has been connected to age-related muscle degeneration,” said Salk Professor Juan Carlos Izpisua Belmonte. “Our study uncovers specific factors that are able to accelerate muscle regeneration, as well as revealing the mechanism by which this occurred.”

In this study, the scientists used two different mouse models to pinpoint the muscle stem-cell-specific or niche-specific changes following addition of Yamanaka factors. They focused on younger mice to study the effects of the factors independent of age.

[Muscle regeneration is mediated by muscle stem cells; they are also called satellite cells, which are located in a niche between a layer of connective tissue (basal lamina) and muscle fibers (myofibers).]

In the myofiber-specific model, they found that adding the Yamanaka factors accelerated muscle regeneration in mice by reducing the levels of a protein called Wnt4 in the niche, which in turn activated the satellite cells.

By contrast, in the satellite-cell-specific model, Yamanaka factors did not activate satellite cells and did not improve muscle regeneration, suggesting that Wnt4 plays a vital role in muscle regeneration – the observations from this study could eventually lead to new treatments by reducing Wnt4 levels in skeletal muscle or blocking the communication between Wnt4 and muscle stem cells.

The scientists are currently using newly-developed gene-editing technologies at the Izpisua Belmonte lab to accelerate muscle recovery after injury and improve muscle function.

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