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Am J Physiol Regul Integr Comp Physiol 295: R1231-R1237, 2008. First published August 13, 2008; doi:10.1152/ajpregu.90478.2008
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EXERCISE AND RESPIRATORY PHYSIOLOGY

Caloric restriction optimizes the proteasome pathway with aging in rat plantaris muscle: implications for sarcopenia

Russell T. Hepple,1 Maggie Qin,1 Hideko Nakamoto,2 and Sataro Goto2

1Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Canada; 2Institute of Health and Sports Science and Medicine, Juntendo University Graduate School, Japan

Submitted 7 June 2008 ; accepted in final form 11 August 2008

To gain insight into the significance of alterations in the proteasome pathway for sarcopenia and its attenuation by calorie restriction, we examined protein oxidation and components of the proteasome pathway in plantaris muscle in 8-, 30-, and 35-mo-old ad libitum-fed (AL) rats; and in 8-, 35-, and 40-mo-old calorie-restricted (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 such increase in CR rats. Protein levels of the ubiquitin ligases MuRF1 and MAFbx increased similarly with aging in both AL and CR rats. On the other hand, 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 that differences in activity were not related to differences in proteasome function with aging. Interestingly, the plot of muscle mass vs. 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 calorie restriction better protects skeletal muscle function than muscle mass with aging (Hepple RT, Baker DJ, Kaczor JJ, Krause DJ, FASEB J 19: 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 calorie restriction optimizes the proteasome pathway to preserve skeletal muscle function at the expense of modest muscle atrophy.

oxidative stress



Address for reprint requests and other correspondence: R. T. Hepple, Faculty of Kinesiology, Univ. of Calgary, 2500 Univ. Dr. NW, Calgary, AB, Canada T2N 1N4 (e-mail: hepple{at}ucalgary.ca)







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