Contractile Activity-Induced Signaling Mechanisms in Aged Skeletal Muscle: Influence on Mitochondria

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Date

2019-03-05

Authors

Carter, Heather Nadine

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Abstract

The process of aging has an influential impact on the quality of skeletal muscle. With advancing age, even in the absence of disease, skeletal muscle has been acknowledged to decline in quantity and quality, a phenomenon referred to as sarcopenia. Currently, the mechanisms which instigate this process remain incompletely defined. However, considerable research has occurred surrounding the role of the mitochondria and their potential to contribute to sarcopenia. Mitochondria are cellular powerhouses supplying the majority of biochemical energy through ATP generation. Mitochondria require proper maintenance within the cellular milieu and this occurs through a balance between the biogenesis and mitophagic degradation of the organelles. Interestingly, exercise is a potent stimulus for both of these cellular pathways. In this work, we sought to examine aspects of mitochondrial biogenesis and mitophagy in aged skeletal muscle to determine how they may change compared to young subjects and whether these processes remain responsive to exercise, in the face of aging. We examined the transcription of PGC-1, a key player in the synthesis of mitochondria. PGC-1 has been acknowledged to decline in aged skeletal muscle, however whether this is due to impaired transcription, was previously unexplored. We identified that PGC-1 transcription was reduced basally in aged muscle compared to their younger counterparts. Interestingly, the gene remained responsive to an acute bout of contractile activity. We next assessed the degree of autophagy and mitophagy flux in aged skeletal muscle, at rest and following adaptation to chronic contractile activity (CCA). Aged muscle exhibited increased mitophagic turnover compared to young muscle, in contrast to prevalent notions in the literature. Following CCA, evaluation of mitophagic flux revealed a decrease in organelle turnover, likely due to an improvement in organelle quality. Taken together, the significance of this research is that we have uncovered the molecular basis for the decline in mitochondrial content in aging muscle. Furthermore, exercise is capable of restoring a healthy mitochondrial pool through restoration of the balance between biogenesis and mitophagy.

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Physiology

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