Impact of Aging and Exercise on Mitochondrial Quality Control in Skeletal Muscle

Yuho Kim, Matthew Triolo, David A Hood, Yuho Kim, Matthew Triolo, David A Hood

Abstract

Mitochondria are characterized by its pivotal roles in managing energy production, reactive oxygen species, and calcium, whose aging-related structural and functional deteriorations are observed in aging muscle. Although it is still unclear how aging alters mitochondrial quality and quantity in skeletal muscle, dysregulation of mitochondrial biogenesis and dynamic controls has been suggested as key players for that. In this paper, we summarize current understandings on how aging regulates muscle mitochondrial biogenesis, while focusing on transcriptional regulations including PGC-1α, AMPK, p53, mtDNA, and Tfam. Further, we review current findings on the muscle mitochondrial dynamic systems in aging muscle: fusion/fission, autophagy/mitophagy, and protein import. Next, we also discuss how endurance and resistance exercises impact on the mitochondrial quality controls in aging muscle, suggesting possible effective exercise strategies to improve/maintain mitochondrial health.

Figures

Figure 1
Figure 1
Aging is associated with reductions in mitochondrial biogenesis. Initial signaling through (1) AMPK and (2) SIRT1 is reduced with aging, thereby reducing (3) PGC-1α coactivation and (4) p53 activation of (5) NUGEMP expression, leading to a decrease in (6) PGC-1α protein and (7) mitochondrial targeted proteins. However, aging is associated with increased (8) TFAM and (9) p53 which has the capacity to enhance (10) mtDNA replication. Depending on age, this mtDNA may contain elevated mutations and may not promote efficient biogenesis in skeletal muscle.
Figure 2
Figure 2
Exercise and mitochondrial dynamics in aging muscle. Endurance exercise training increases mitochondrial biogenesis in aging muscle, although its extent may be lessened compared to young muscle. In addition, chronic exercise leads to a global upregulation of protein markers for mitochondrial dynamic controls: fusion/fission, autophagy/mitophagy, and protein import. Since the lysosomal system has been suggested as a key player for governing mitochondrial quality control, the role of TFEB, a master regulator of lysosomal biogenesis, appears to be important and its relationship with PGC-1α may be also considerable for the exercise-inducible upregulation of mitochondrial turnovers. However, more studies are needed to clarify the effects of endurance training exercise on the mitochondrial turnover systems in aging muscle.

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