Mitochondria as a Target for Mitigating Sarcopenia

Abstract

Sarcopenia is the loss of muscle mass, strength, and physical function that is characteristic of aging. The progression of sarcopenia is gradual but may be accelerated by periods of muscle loss during physical inactivity secondary to illness or injury. The loss of mobility and independence and increased comorbidities associated with sarcopenia represent a major healthcare challenge for older adults. Mitochondrial dysfunction and impaired proteostatic mechanisms are important contributors to the complex etiology of sarcopenia. As such, interventions that target improving mitochondrial function and proteostatic maintenance could mitigate or treat sarcopenia. Exercise is currently the only effective option to treat sarcopenia and does so, in part, by improving mitochondrial energetics and protein turnover. Exercise interventions also serve as a discovery tool to identify molecular targets for development of alternative therapies to treat sarcopenia. In summary, we review the evidence linking mitochondria and proteostatic maintenance to sarcopenia and discuss the therapeutic potential of interventions addressing these two factors to mitigate sarcopenia.

Vitamin D and Sarcopenia: Potential of Vitamin D Supplementation in Sarcopenia Prevention and Treatment

“…Mitochondrial dysfunction results in mild but chronic inflammation due to increased production of reactive oxygen species, leading to qualitative/quantitative deterioration of skeletal muscle, which is thought to be one of the major causes of sarcopenia onset [ 63 ]. Reports suggest that 1,25(OH) 2 D supplementation improves the function of mitochondrial oxidative phosphorylation in the skeletal muscle in vitamin D deficient humans [ 64 ].…”

Impact of Melatonin on Skeletal Muscle and Exercise

“…At a cellular level, to alleviate sarcopenia is necessary to improve mitochondria number and turnover of contractile proteins and anti-oxidant enzymes [126]. A proper mitochondrial turnover is crucial in muscle adaptation to exercise given that abnormal proteostasis leads to loss of contractile proteins in aged muscles [127,128]. However, despite controlled physical activity, complete muscle restoration is impossible due to unavoidable oxidative deterioration of fast glycolytic fibers and enhanced expression of age-related genes insensitive to exercise benefit [129,130].…”

Testosterone improves muscle fiber asset and exercise performance in a metabolic syndrome model

“…Similar results were found also in terms of both ATP production, as marker of mitochondrial respiration, and in terms of mitochondrial mass, as evaluated by TOM20 protein expression. Noteworthy, mitochondrial dysfunction is crucially contributing to the complex etiology of sarcopenia even in the context of metabolic diseases (Coen et al 2018). Treatment in male mice increases the expression of genes involved in mitochondrial biogenesis and heat production in skeletal muscle via an AR-dependent pathway (Usui et al 2014).…”