Fig. 6. Model of damage/repair cycle changes during ageing. In adult muscle, nuclei lost through damage or exercise may lead to transient domain size increase but are rapidly replaced from myogenic cells, returning domain size to the set point, without significant alteration in fibre size. In ageing muscle, reduced SC function might lead to delayed nuclear replacement and the start of domain size increase. In aged muscle, poor SC function, particularly in large fibres, exacerbates the cycle of decline. Over time, the inability of nuclei to support an excessive domain size leads to cytoplasmic atrophy, returning domain size to the normal set point typical of smaller fibres, which have fewer nuclei and smaller domain sizes than large fibres in healthy adults.