Mechanisms of Skeletal Muscle Mass Regulation and Muscle Memory

Changes in muscle mass and force are mainly related to changes in fiber size. In eukaryotes, DNA-content and cell size are generally correlated, suggesting the existence of a DNA-template limitation. This might be particularly important in the skeletal muscle fiber syncytia, which contain 30%-50% less DNA per cytoplasmic volume than most cells. Muscle fibers display a correlation between fiber size and myonuclear number, and genetically reducing the number reduces the size. Even so, the cytoplasmic volume per nucleus is larger in larger cells, demonstrating some flexibility in each nucleus' ability to "produce volume." De novo hypertrophy leads to accrual of myonuclei, which do not seem to be lost; the "extra" nuclei might serve as a mechanism for muscle memory. A complementary hypothesis is that muscle memory relies on each nucleus' ability to provide protein related to persistent/long-lasting epigenetic traces. A few epigenetically altered loci have been suggested, but there is currently no consensus between various studies as to which these are.