Regeneration of old muscles
One of the many manifestations of aging is the loss of muscle mass, or sarcopenia, which leads to limited mobility in the elderly. To overcome sarcopenia, researchers from the Salk Institute studied ways to accelerate muscle tissue regeneration using a combination of Yamanaki reprogramming factors (OSKM – Oct-3/4, Sox2, Klf4 and c-Myc), which are commonly used in stem cell research.
The induction of Yamanaki factors in muscle fibers increases the number of myogenic precursors; control is at the top, treatment is at the bottom. The marker of muscle stem cells Pax7 is colored red, the nuclei of myocytes are blue. Source: Salk Institute.
The combination of factors used in this study are named after Nobel laureate Shinya Yamanaki, who used them to obtain induced pluripotent stem cells for the first time in the world. Yamanaka factors control the copying of DNA for subsequent translation into proteins. Previously, the group showed that these factors can rejuvenate cells and promote tissue regeneration in vivo, but how this happens was not known.
Muscle regeneration is mediated by myogenic precursors, which are located in a niche between a layer of connective tissue (basal plate) and muscle fibers (myofibrils). In the study, the team used two different mouse models to identify muscle stem cell-specific changes after the expression of Yamanaki factors. In one model, local expression of Yamanaki factors was performed directly in myofibrils, in the other – in progenitor cells. Models were created from young mice to study the influence of age-independent factors.
The expression of Yamanaki factors in myofibrils induced the activation of muscle stem cells, accelerating muscle regeneration in mice by reducing the level of Wnt4 protein, which, in turn, activates myogenic precursors. On the contrary, the expression of Yamanaki factors directly in myogenic precursors did not enhance muscle regeneration, proving that Wnt4 plays a key role in the process of muscle regeneration.
According to the authors, the results of this study will help to create new methods of treating sarcopenia by directly disabling the Wnt4 gene or blocking its binding to myogenic precursors. Researchers are also exploring other ways to rejuvenate myocytes, including using mRNA and genetic engineering.
Article C.Wang et al. In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Salk Institute: New study shows how to boost muscle regeneration and rebuild tissue.