Every cell contains hundreds of mitochondria, the descendants of ancient symbiotic bacteria that have their own DNA, replicate to maintain their numbers, and are responsible for generating the chemical energy store molecule adenosine triphosphate (ATP) to power the cell. Mitochondria, like all cell structures, are constantly damaged. Damaged and dysfunctional mitochondria are removed via the cell maintenance process of mitophagy. With age, this quality control falters, while the expression of genes necessary for mitochondrial function change for the worse. Mitochondrial DNA becomes damaged in ways that further degrade function. As a result, cell and tissue function also becomes disrupted, contributing to the many manifestations of degenerative aging. The focus here is on muscle tissue, but analogous stories can be told for any tissue in the aging body.
As the global population trends toward aging, the number of individuals suffering from age-related debilitating diseases is increasing. With advancing age, skeletal muscle undergoes progressive oxidative stress infiltration, coupled with detrimental factors such as impaired protein synthesis and mitochondrial DNA (mtDNA) mutations, culminating in mitochondrial dysfunction. Muscle stem cells (MuSCs), essential for skeletal muscle regeneration, also experience functional decline during this process, leading to irreversible damage to muscle integrity in older adults.
A critical contributing factor is the loss of mitochondrial metabolism and function in MuSCs within skeletal muscle. The mitochondrial quality control system plays a pivotal role as a modulator, counteracting aging-associated abnormalities in energy metabolism and redox imbalance. Mitochondria meet functional demands through processes such as fission, fusion, and mitophagy. The significance of mitochondrial morphology and dynamics in the mechanisms of muscle regeneration has been consistently emphasized. In this review, we provide a comprehensive summary of recent advances in understanding the mechanisms of aging-related mitochondrial dysfunction and its role in hindering skeletal muscle regeneration. Additionally, we present novel insights into therapeutic approaches for treating aging-related myopathies.
Link: https://doi.org/10.1...658-025-00771-1
View the full article at FightAging
