Muscle aging and chromatin
A new sign of muscle aging has been discovered
Scientists at the Hong Kong University of Science and Technology have discovered a new sign of aging in muscle stem cells (MuSC). It turned out that chromatin, the main substance of chromosomes, shows excessive activity in old stem cells, which distinguishes them from young MuSC. The results of the study are published in the journal iScience (Dong et al., Global chromatin accessibility profiling analysis reveals a chronic activation state in aged muscle stem cells).
It is known that adult stem cells, which are involved in the regeneration of tissues, for example, skeletal muscles, are capable of being at rest for a long time, and when injured, they activate and begin to divide. Then some activated muscs return to the resting state for self-renewal and replenishment of the stem cell pool. The key compound involved in this process is the Pax7 protein, and its depletion leads to depletion of the pool due to the stoppage of cell division.
Chromatin is a substance that consists of DNA and its associated proteins. It can have two states: condensed, in which its structure is tightly packed (heterochromatin), and a less dense state — euchromatin. Heterochromatin is characterized by the fact that the DNA in its composition is not transcribed, that is, it does not participate in the synthesis of RNA and proteins. This ensures the regulation of the cellular genome, since each cell type, including MuSC, must have its own set of activated genes.
The researchers studied changes in chromatin openness in young and old muscs during quiescence, early activation and regeneration. For the analysis of euchromatin, the ATAC-seq sequencing method is used, which identifies open areas of the genome by artificial fragments embedded in it — adapters. It turned out that in old stem cells chromatin is characterized by greater openness, that is, a chronic activated state. As a result, the resting state of these cells is often interrupted, as a result of which the ability to regenerate deteriorates. In addition, the openness of chromatin contributes to the increased activity of genes associated with the development of cancer.
The scientists also managed to discover key Pax7 regulators called enhancers — these are DNA regions that can enhance the activity of a particular gene. Experimental blocking of enhancers led to Pax7 protein deficiency and stem cell dysfunction. The activity of these enhancers decreased in old dormant cells, which may be explained by the action of some other factors. According to scientists, if it is possible to find a way to preserve the activity of enhancers in old cells, this will allow them to "rejuvenate" them.
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