Читать книгу Sarcopenia - Группа авторов - Страница 39

There is strong evidence that apoptosis, the process of programmed cell death, plays a primary role in the pathogenesis of the age‐associated decline of muscle mass and strength. Studies that compared skeletal muscle tissues from younger and older rats reported high levels of apoptosis and connected the degree of muscle mass decline with the severity of apoptotic DNA fragmentation [80–82]. Apoptosis appears to be more frequent among type II fibers, possibly consequently to the higher susceptibility to TNF‐alpha signaling pathway. In skeletal muscle fibers, apoptosis can be induced either through a mitochondria‐independent or a mitochondria‐dependent mechanism, and it is not established which one of these pathways contributes to the accelerated decline of muscle mass and strength that eventually leads to sarcopenia. In mitochondria, apoptosis is initiated by mitochondrial matrix accumulation of Ca²⁺ which leads to the opening of the permeability transition pore (MPTP), a large non‐selective channel in the inner mitochondrial membrane. The opening of the MPTP increases concentrations of ROS, elicits membrane depolarization, and releases cytochrome c into the cytosol, activating the apoptotic program through a number of intermediate steps, including the activation of caspase‐9 and caspase‐3. Apoptosis includes reorganization of the cytoskeleton, arrest of cell replication, fragmentation of the nuclear membrane and the DNA, and eventually cell death. There is some but not concluding evidence that the threshold for apoptosis activation is increased in aging skeletal muscle, especially in humans. Further research is needed in this field. Interestingly, exercise and dietary restriction attenuate apoptosis with aging [81, 82]. Targeting apoptosis might be an effective intervention to counteract age‐related muscle wasting. However, more mechanistic studies are required before potentially effective treatment strategies can be developed.