Insulin resistance with aging may be responsible for impaired glycogen synthesis in the skeletal muscle of aged rats and contribute to the well-known decreased ability to respond to stress with aging. For this reason, to assess the ability of the skeletal muscle to utilize glucose for glycogen synthesis during aging, the time course of glycogen synthesis was continuously monitored by C-13 nuclear magnetic resonance for 2 h in isolated [C-13] glucose-perfused gastrocnernius-plantaris muscles of 5-day food-deprived adult (6-8 months; n=10) or 5-day food-deprived aged (22 months; n = 8) rats. [C-13] glucose (10 mmol/L) perfusion was carried out in the presence or absence of an excess of insulin (1 mu mol/L). Food deprivation only decreased glycogen level in adult rats (8.9 +/- 2.4 mu mol/g in adults vs. 35.6 +/- 2.4 mu mol/g in aged rats; P < .05). In the presence of an excess of insulin, muscle glycogen synthesis was stimulated in both adult and aged muscles, but the onset was delayed with aging (40 min later). In conclusion, this study highlights the important role of glycogen depletion in stimulating glycogen synthesis in muscles. Consequently, the absence of glycogen depletion in response to starvation in aged rats may be the origin of the delay in insulin-stimulated glycogen synthesis in the skeletal muscle. Glycogen synthesis clearly was not impaired with aging.