PURPOSE: We have assessed the effect of acute exercise on cytokine gene expression in skeletal muscle tissue from young and elderly men. METHODS: Physically active young (23–35 yr, n = 15) and elderly (66–78 yr, n = 15) men participated in this study. Subjects performed 45 min of downhill running (−16% decline) at 75% VO2 max on a treadmill. A biopsy of vastus lateralis was obtained 24 hours before and 72 hours after the exercise bout. mRNA levels for catabolic (TNF-α, IL-1β, IL-6, TGF-β1 and myostatin) and anabolic (IGF-1 and IL-15) cytokines were assessed using semi quantitative real-time PCR. RESULTS: Following acute exercise, TNF-α mRNA levels increased 2.9- and 1.8- fold (P < 0.01) in the young (Y) and old (O) groups, respectively. Likewise, IL-1β mRNA levels in Y and O groups increased 3.1- and 1.6-fold, respectively (P < 0.01). In contrast, IL-6 mRNA levels increased 3.7-fold in Y group (P < 0.05), but did not change in the O group. TGF-β1 mRNA levels in Y and O groups increased 4.0- and 1.6-fold, respectively (P < 0.01). Myostatin mRNA levels in the Y group decreased 30% (P < 0.05), whereas there was no change in the O group. Muscle type IGF-1 (mechano growth factor) mRNA levels increased 2.0-fold in Y group (P < 0.05), but there was no change in O group. IL-15 mRNA levels did not change in either group. CONCLUSION: Our results indicate that age may impair the adaptive response of skeletal muscles to acute exercise by preventing changes in sarcoactive cytokine gene expression necessary for adequate remodeling of injured skeletal muscle tissues. The age-acquired impediment in adaptive cytokine gene expression may contribute to the etiology of sarcopenia.