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Articles in PresS, published online ahead of print February 13, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00598.2001
Submitted on December 20, 2001
Accepted on February 10, 2002
1 Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA
2 Physiology, University of Nijmegen, Nijmegen, Netherlands
* To whom correspondence should be addressed. E-mail: salway{at}hsc.wvu.edu.
Basal mRNA levels but not protein levels of the myogenic transcription factors (MRF) MyoD, myogenin, and MRF4 are greater in muscles of aged animals than adult animals. Muscles from aged animals respond to a hypertrophic stimulus with an attenuated increase in MRF expression and muscle enlargement as compared to muscles from young adult animals. The purpose of this study was to determine if during hypertrophy, mRNA levels of repressors to the MRFs are greater in muscles from aged (33 mo., n=14) as compared to adult animals (9 mo., n=17). Hypertrophy of the plantaris was achieved by denervating its synergists. After 14 days, plantaris muscles in the overloaded limb were ~25% and 6% larger in young adult and aged rats, respectively, as compared to the contralateral limb. Cyclophilin did not differ (p=0.83) between age groups and was therefore used as an internal control. Hypertrophied muscles of young rats had elevated mRNA and protein levels of myogenin (1700% and 1100%, respectively) and MyoD (625% and 430%, respectively) as compared to control muscles, but myogenin and MyoD levels did not increase with hypertrophy in muscles of aged rats. Id-1, Id-2 and Id-3 mRNA and protein repressor levels were 150-700% and 200-6000% greater, respectively, in control muscles of aged vs. young adult rats (p<0.05) while aging or hypertrophy did not affect levels of Mist1 and Twist levels. Hypertrophied muscles of young adult rats had greater mRNA and protein levels of Id-1 (195% and 480%, respectively) and Id-2 (85% and 95%, respectively) as compared to control muscles. BAX and caspase 9 protein levels were 9500% and 300% greater, respectively in both control and hypertrophied muscles of aged rats as compared to young adult rats. Id, BAX and caspase 9 protein levels were positively correlated and all were higher in muscles of aged rats. These data suggest that an elevation of repressor transcripts at old age might activate apoptotic pathways involving BAX. We suggest that this mechanism contributes to sarcopenia at old age, and together with the attenuated change of MRF levels during hypertrophy provides an explanation for the suppressed hypertrophic response at old age.
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