The Failure of Mitophagy as a Contributing Cause of Sarcopenia

Here, researchers discuss the role of mitochondrial quality control in sarcopenia. Sarcopenia is the name given to the later stages of the loss of muscle mass and strength characteristic of aging. Muscle is an energy-hungry tissue, and the age-related decline in mitochondrial activity is therefore likely a contributing factor in this progressive loss of function. Mitochondria are the power plants of the cell, responsible for generating the ATP molecules that store chemical energy needed to power cellular processes. Every cell contains a herd of hundreds of mitochondria, which are removed and recycled when they become worn or broken by the quality control process of mitophagy. Unfortunately mitophagy becomes less efficient with age, for reasons yet to be fully explored, but which are likely connected to changes in mitochondrial dynamics.

Mitochondria have strong impacts on the maintenance of cellular viability, including ATP production, oxidative phosphorylation (OXPHOX) homeostasis, calcium buffering, and apoptosis. Therefore, healthy quality control is crucial for the preservation of intracellular homeostasis of muscle cells with aging. The mitochondrial quality control (MQC) includes mitochondrial proteostasis, biogenesis, dynamics and autophagy. Orchestrated mechanisms contain several cellular factors and signaling pathways to ensure the integrity of mitochondria. Mitochondrial biogenesis is responsible for the generation of new mitochondria through the synergistic interaction of the nuclear and mitochondrial genes; mitochondrial dynamics is achieved by continual transformation between fusion and fission to eliminate the accumulation of unhealthy mitochondria; mitochondrial autophagy (mitophagy) is a process of selective removal of the hypofunctional and damaged mitochondria. Adverse alternations in the quality control mechanisms may lead to mitochondrial dysfunction, which can further contribute to muscle wasting and even sarcopenia.

The incidence rate of sarcopenia in the mid-life and elderly population varies according to different age, operational definitions, regions and ethnicities. A number of epidemiological studies have shown that the prevalence of sarcopenia gradually increases with age. It is conservatively estimated that 5%-13% of elderly individuals aged 60-70 years are suffering from sarcopenia. The numbers increase to 11%-50% among those aged 80 or above. Since the number and proportion of the global aging population is rapidly growing, the socio-economic burden of individuals and society may increase due to higher prevalence of sarcopenia. Sarcopenia was formally recognized as a disease in 2016, which attracted additional attention for this degenerative disease. Physical activity is recommended as the primary treatment for sarcopenia to improve muscle strength and mass, although no specific drugs have been developed with therapeutic effects in sarcopenia. In this review, we summarize the potential mechanisms of mitochondrial dysfunction with an emphasis on promising therapeutic interventions to prevent and ameliorate sarcopenia during aging.


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