Studies have been performed in humans to identify changes in gene expression that may account for the relatively weak and variable response of aged muscle to resistance exercise. The gene expression profile of skeletal muscle from elderly (62-75 years old) compared to younger (20-30 years old) men demonstrated elevated expression of genes typical of a stress or damage response. The expression of the majority of these genes was unaffected by a single bout of high-intensity resistance exercise in elderly subjects but was altered acutely by exercise in younger subjects so as to approach the pre-exercise levels observed in older subjects. The inability of muscle from elderly subjects to respond to resistance exercise was also apparent in the expression of inflammatory response genes, which increased within 24 hours of the exercise bout only in younger subjects. Othergenes with potentially important roles in the adaptation of muscle to exercise, showed a similar or even more robust response in older compared to younger subjects. Taken together, these results may help to explain the variable hypertrophic response of muscle from older individuals to resistance training.