Is the myonuclear domain ceiling hypothesis dead?

Muscle fibres are multinuclear cells, and the cytoplasmic territory where a single myonucleus controls transcriptional activity is called the myonuclear domain (MND). MND size shows flexibility during muscle hypertrophy. The MND ceiling hypothesis states that hypertrophy results in the expansion of MND size to an upper limit or MND ceiling, beyond which additional myonuclei via activation of satellite cells are required to support further growth. However, the debate about the MND ceiling hypothesis is far from settled, and various studies show conflicting results about the existence or otherwise of MND ceiling in hypertrophy. The aim of this review is to summarise the literature about the MND ceiling in various settings of hypertrophy and discuss the possible factors contributing to a discrepancy in the literature. We conclude by describing the physiological and clinical significance of the MND ceiling limit in the muscle adaptation process in various physiological and pathological conditions.

Plasticity of skeletal muscle and variability of myonuclear domain / 体力科学

Skeletal muscle fiber has a great ability to hypertrophy during growth and in response to exercise stimuli, and atrophy during aging and in response to disuse. Because the muscle fiber is a multinucleated cell, the region of cytoplasm governed by a single myonucleus (myonuclear domain; MND) is a very important factor for understanding muscle plasticity. Although the MND size varies with fiber type, metabolic property and species, it was considered that the size was maintained constantly during muscle adaptation. Recently, however, there have been many studies demonstrating the variability of the MND size. In some of these studies, it is hypothesized that muscle hypertrophy is achieved by increase in protein synthesis rate until the ‘ceiling’ of MND size and subsequent addition of myonuclei by satellite cell activation. On the other hand, during muscle atrophy, the myonuclei seems to be long lasting as ‘muscle memory’ storing information about previous size to prepare for recovery of muscle fiber. Understanding the variability of MND size more deeply would provide fundamental insights into the mechanism of skeletal muscle plasticity.