Age-related differences in the des IGF-I-mediated activation of Akt-1 and p70 S6K in mouse skeletal muscle.

The ability of des IGF-I to activate Akt-1 and p70 S6K in skeletal muscle with or without acute endurance exercise was examined in young and old mice. Mice were sacrificed 12 h after a moderate intensity treadmill run following an interperitoneal injection of des-IGF-I or saline. Blood and skeletal muscle were collected and IGF-I receptor, Akt-1 and p70 S6K protein contents and their phosphorylation status were determined. Injection of des IGF-I similarly decreased plasma glucose concentration in both young (P<0.01) and old mice (P<0.01) whereas plasma insulin and total IGF-I levels of young and old mice were not significantly changed by des IGF-I. Total IGF-I receptor protein and IGF-1 receptor phosphorylation were lower in aged mice (P<0.05). Basal phosphorylation of Akt-1 was lower in aged skeletal muscle (P<0.01) and this was not caused by changes in Akt-1 protein. In both young (P<0.01) and aged (P<0.05) mice, des IGF-I significantly increased the phosphorylation of Akt-1 at Ser 473. However, a des IGF-I-mediated increase in the p70 S6K phosphorylation (P<0.01) was only seen in young mice. Prior exercise decreased the total plasma IGF-I level in the presence of des IGF-I in aged mice. Des IGF-I-mediated Akt-1 and p70 S6K phosphorylation was not changed by exercise in either young or old mice. It is concluded that there was an aging-related resistance at the p70 S6K level in mouse skeletal muscle that could not be restored by prior exercise and this resistance is associated with lower IGF-I receptor number and Akt-1 phosphorylation in the aged skeletal muscle.