If myonuclear loss initiates muscle wasting, it should precede the loss of muscle mass. As aging affects muscle plasticity, the time-course of muscle atrophy during disuse may differ between young and old animals. To investigate this, gastrocnemius muscles of 5-and 25-month-old rats were exposed to 1, 2, or 4 weeks of denervation, whereas the contralateral gastrocnemius muscles served as controls. Muscle fibers of each type responded similarly to 4 weeks of denervation. For both ages most of the atrophy (36%; P < 0.001) occurred in the first 2 weeks. In young-adult muscles, the myonuclear number remained constant, but in old muscles it decreased to below control level after 4 weeks of denervation (P < 0.05). Despite this differential response, myonuclear domain size decreased similarly at both ages (P < 0.001). In both young-adult and old rats, denervation-induced atrophy was not preceded by a loss of myonuclei.

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We investigated whether myonuclear number increases in proportion to the increase in fiber size during maturational growth of skeletal muscle. Thoraco-abdominal muscle tissue was obtained from twenty 6-day to 15-year-old boys and girls during cardiothoracic surgery. Cross-sections were stained by anti-laminin for the basal lamina and by DAPI to identify nuclei. Basal lamina was traced on digital images to measure the fiber cross-sectional area (FCSA). Nuclei located within the basal lamina were considered myonuclei if pax7-negative and satellite cell nuclei if pax7-positive. Samples of two children were excluded from analysis because of clear signs of hypoxia as shown by positive carbonic anhydrase IX staining. Linear regression showed that FCSA increased with age by 187 lm 2 Áper annum (R 2 ¼ 0.90; P < 0.001). Satellite cell density showed a dramatic decrease in the first months of life, but this was not accompanied by an increase in myonuclei per muscle fiber cross-section. Till four years of age the number of myonuclei per muscle fiber cross-section remained relatively constant but increased thereafter. Myonuclear domain size showed a steep increase during infancy and reached adult values in the young adolescent phase.