Role of apoptosis in sarcopenia.
Skeletal muscle atrophy and the loss of myofibers contribute to sarcopenia, a condition associated with normal aging. However, relatively little is known regarding the relevance of apoptosis to skeletal muscle homeostasis and the possible mechanisms involved, although evidence suggests that apoptosis may play a role during muscle aging. By age 80 it is estimated that humans generally lose 30%-40% of skeletal muscle fibers, particularly from muscles containing type II fibers such as the vastus lateralis muscle. Studies using rodents show that between a 20%-50% loss in muscle fibers occurs depending on the specific fiber type studied. Caspases (cysteine-dependent, aspartate-specific proteases) such as caspase-3 play an important role in mediating cell death in that many of the apoptotic signaling pathways, such as the mitochondrial-mediated, receptor-mediated, and sarcoplasmic-reticulum-mediated pathways, converge at caspase-3 in the caspase cascade. Studies show that with age the levels of several caspases are significantly increased. Therefore, the activation of these proteolytic caspases may be partly responsible for the initiation of muscle protein degradation, loss of muscle nuclei, which is associated with local atrophy, and finally into cell death of the myocyte.
Leeuwenburgh
Christiaan
C
Biochemistry of Aging Laboratory, University of Florida, Gainesville 32611, USA. cleeuwen@hhp.ufl.edu
D000818:Animals; D017209:Apoptosis; D006801:Humans; D009133:Muscular Atrophy / Q000503:physiopathology*