Matters of fiber size and myonuclear domain: Does size matter more than age?

Introduction: The relationship between fiber size and myonuclear content is poorly understood. Methods: Biopsy cross-sections from young and old trained and untrained healthy individuals were analyzed for fiber area and myonuclei, and 2 fiber-size-dependent cluster analyses were performed. Results: When comparing fibers of similar size, no effect of training or age was found for myonuclear domain. There was a linear relationship between fiber area and myonuclei per fiber (r = 0.99; P < 0.001) and a non-linear relationship between fiber area and domain (r = 0.97–0.99; P < 0.0001), with a markedly smaller domain in fibers <3,000 µm2. A higher proportion of type II fibers <3,000 µm2 was observed in the old subjects. Conclusions: These findings suggest that age-related reductions in myonuclear domain size could be explained by the greater proportion of small fibers. The data also highlight the usefulness of determining fiber-size-based clusters for gaining mechanistic insight into the relationship between skeletal muscle fiber size and myonuclear content