Abstract
Force generation by skeletal muscle declines during ageing. This change contributes substantially to increased physical dependency in the aged. The decline in muscle mass is not entirely accounted for by a fall in muscle fibre number: fibres appear to lose volume. Here we review data that address the fundamental question of how muscle fibres regulate their size. In muscles, the problem has two elements because muscle fibres are syncitia formed by the fusion of mononucleate precursor cells. Thus, fibre size appears to be regulated both by the number of nuclei incorporated into each fibre and by a second variable, the volume of cytoplasm that each nucleus supports. We conclude that understanding of the regulation of muscle cell size is in its infancy and highlight directions that might productively be pursued.