Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Abstract

Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fibre branching

“…Alterations in the NMJ are a critical contributor to sarcopenia, but it is not clear whether defective mitochondrial function precede or follow changes in NMJ and skeletal muscle atrophy and contractile dysfunction . Our laboratory and others previously demonstrated that denervation plays a causal role in AchR fragmentation and degeneration, leading to skeletal muscle atrophy .…”

“…Changes in redox status have a major impact on cellular and physiological processes and may underlie many functional deficits associated with aging and oxidative stress. 3,45 Removal of H 2 O 2 is catalysed by the antioxidant enzymes catalase, GSH peroxidase, and peroxiredoxins. GSH peroxidase and peroxiredoxins require oxidation of GSH and thioredoxin, respectively.…”

Comparison between the effect of human Wharton’s jelly–derived mesenchymal stem cells and levetiracetam on brain infarcts in rats

“…It also reduced brain damage in experimental subarachnoid hemorrhage and closed head trauma. Extracellular SOD isoenzyme incorporates Cu-Zn as a cofactor and is present in extracellular fluids and interstitial spaces of tissues 10 Caspases are a family of cysteinyl aspartate-specific proteinases. 3 LEV acts as a neuroprotective through its interaction with a target protein of the synaptic vesicle SV2.…”

Evaluation of Redox Activity of Human Myocardium‐derived Mesenchymal Stem Cells by Scanning Electrochemical Microscopy

“…Therefore, the intracellular redox homeostasis of cardiac‐resident and non‐resident mesenchymal stem cells is extremely important for the proper functioning of muscle tissue . The redox imbalance is mainly caused by the excess of reactive oxygen species (ROS) or declined antioxidant system and is closely related to cardiovascular diseases and aging . Therefore, the investigation of changed intracellular redox environment of human dilated myocardium‐derived mesenchymal stem cells MSC, compared to the healthy heart cells, is of further therapeutic importance.…”