The role of apoptosis in sarcopenia: The effects of age and caloric restriction on skeletal muscle apoptosis

Sarcopenia may be partly due to a loss in total fiber number by apoptosis. We have investigated age-related alterations in apoptotic stimuli, such as mitochondrial dysfunction, as well as changes in apoptotic markers and adaptations in apoptotic pathways. We studied apoptosis in the gastrocnemius muscle focusing on the mitochondrial-mediated apoptotic pathway, including caspase-independent apoptosis by apoptosis inducing factor, the endoplasmic-reticulum-mediated pathway, and the receptor-mediated pathway. We report that the rate of apoptosis does increase in aged muscle tissue and that there is a highly significant correlation between the apoptotic index and muscle mass suggesting that apoptosis does contribute to sarcopenia. Many adaptations occur in the mitochondrial-mediated and endoplasmic-reticulum-mediated apoptotic pathways, but not the receptor-mediated pathway. We found that age-related alterations in the mitochondrial-mediated pathway act to protect against apoptosis and that this pathway may be inhibited. Alterations in the endoplasmic-reticulum-mediated pathway may contribute to apoptosis and loss of fibers with age.;Caloric restriction is a powerful anti-aging intervention. Therefore, we used caloric restriction as an intervention to reduce oxidative stress and mitochondrial dysfunction and to prevent fiber loss with age. We found that lifelong caloric restriction attenuated the rate of apoptosis in aged muscle tissue and generally reversed most of the age-related alterations in the apoptotic pathways studied. However, we did not detect any effects on the receptor-mediated pathway. Our results suggest that apoptosis does contribute to age-related fiber loss and that the endoplasmic-reticulum-mediated apoptotic pathway may be playing a significant role in the pathogenesis of sarcopenia.