Apoptosis in skeletal muscle with aging.
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.
Dirks
Amie
A
University of Florida, Biochemistry of Aging Laboratory, College of Health and Human Performance, Center for Exercise Science, College of Medicine, Gainesville, Florida 32611, USA.
Leeuwenburgh
Christiaan
C
D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009707:Nucleosomes / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D051028:bcl-2-Associated X Protein
C506594:Apaf1 protein, rat; D053477:Apoptotic Protease-Activating Factor 1; C494828:Bax protein, rat; D003574:Cytochrome c Group; D005609:Free Radicals; D009707:Nucleosomes; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004720:Endonucleases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases