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Am J Physiol Regul Integr Comp Physiol 282: R519-R527, 2002. First published October 18, 2001; doi:10.1152/ajpregu.00458.2001
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Vol. 282, Issue 2, R519-R527, February 2002

Apoptosis in skeletal muscle with aging

Amie Dirks and Christiaan Leeuwenburgh

University of Florida, Biochemistry of Aging Laboratory, College of Health and Human Performance, Center for Exercise Science, College of Medicine, Gainesville, Florida 32611

Sarcopenia may be partly due to a loss in total fiber number by apoptosis. We have investigated age-related alterations in the mitochondria-mediated pathway leading to apoptosis in the gastrocnemius muscle from 6-mo-old and 24-mo-old male Fisher 344 rats. Apoptosis (mono- and oligonucleosome fragmentation) in the gastrocnemius muscle was increased by 50% in the old rats compared with the adult animals. Furthermore, there was a significant correlation between cytosolic cytochrome c and caspase-3 activity, although neither cytochrome c nor caspase-3 activity increased significantly with age. Furthermore, there was a significant correlation between caspase-3 activity and mono- and oligonucleosome fragmentation in the old rats only. Mitochondrial Bcl-2 and Bax were not altered with age. In vitro experiments demonstrated that activation of the caspase cascade in skeletal muscle might be limited by procaspase-9 activation. This is the first study to explore the role of apoptosis in sarcopenia and suggests that subtle changes in apoptosis are involved.

free radicals; oxidative stress; apoptotic protease activating factor-1; Bcl-2 family; cytochrome c; caspases; mitochondria


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