To gain insight into the significance of alterations in the proteasome pathway for sarcopenia and its attenuation by caloric restriction (CR), we examined protein oxidation and components of the proteasome pathway in plantaris muscle in 8 mo old, 30 mo old and 35 mo old AL rats; and in 8 mo old, 35 mo old and 40 mo old CR rats. We hypothesized that CR rats would exhibit a lesser accumulation of protein carbonyls with aging and that this would be associated with a better maintenance of skeletal muscle proteasome activity and function with aging. Consistent with this view, whereas AL rats had a significant increase in protein carbonylation with aging, there was no increase in CR rats. The protein levels of the ubiquitin ligases MuRF1 and MAFbx increased similarly with aging in both AL and CR rats. On the other hand, the chymotrypsin-like activity of the proteasome increased with aging more gradually in CR rats, and this increase was paralleled by increases in the expression of the C2 subunit in both groups, suggesting the differences in activity were not related to differences in proteasome function with aging. Interestingly, the plot of muscle mass versus proteasome activity showed that the oldest animals in both diets had a lower muscle mass than would be predicted by their proteasome activity, suggesting that other factors explain the acceleration of sarcopenia at advanced age. Since CR better protects skeletal muscle function than muscle mass with aging (FASEB J. 19[10]: 1320-1322, 2005), and our current results show that this protection of function is associated with a prevention of oxidative protein damage accumulation, we suggest that CR optimizes the proteasome pathway to preserve skeletal muscle function at the expense of modest muscle atrophy.