Aging of humans is associated with a decrease in muscle fiber number and cross-sectional area (CSA), resulting in a net loss of skeletal muscle mass. As satellite cells play an important role in skeletal muscle adaptation to anabolic stimuli and injury, we determined whether the number of satellite cells was lower in older men than young men. In addition, we determined the effects of graded doses of testosterone on muscle fiber area, satellite cell number and replication in healthy, older men. Healthy, old men, (60-75 yrs) received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600mg testosterone enanthate IM weekly for 20 wks. Muscle biopsies were obtained from vastus lateralis before and after treatment and immunohistochemical staining and electron microscopy were used to perform fiber typing and to identify dividing and apoptotic satellite cells.
Results The number and CSA of type I and type II fibers did not differ among five groups at baseline. Mean CSA of type II fibers was significantly smaller in older men at baseline (3157+55 μm2) than young men (3710±134 μm2). Testosterone administration in older men was associated with a dose-dependent increase in CSA of both type I (increase 384±286; 633±395; and 1507±313 μm2 respectively at 125, 300 and 600 mg doses) and II fibers (increase: 502±397; 1159±525 μm2 respectively at 300 and 600 mg doses). The number of satellite cells also increased dose-dependently at the three highest doses (5%, 10%, and 12% increase at 125, 300 and 600 mg doses). The percent of muscle fibers showing proliferating satellite cells, assessed by PCNA staining, was significantly lower in older men at baseline than young men; testosterone treatment was associated with an increase in the number of PCNA+ satellite cells (baseline 5.5±4.5 vs 15.8±5.5% after treatment).
Conclusion Although muscle fiber CSA and satellite cell number are lower in older men than young men, older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber area and satellite cell number. Testosterone-induced increase in satellite cell number is associated with an increase in satellite cell replication.
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