Abstract
BackgroundSarcopenia is the progressive loss of skeletal muscle that contributes to the decline in physical function during aging. A higher level of oxidative stress has been implicated in aging sarcopenia. The current study aims to determine if the higher level of oxidative stress is a result of increased superoxide (O2‾) production by the NADPH oxidase (NOX) enzyme or decrease in endogenous antioxidant enzyme protection.MethodsFemale Balb/c mice were assigned to 4 age groups; 6, 12, 18 and 24 months. Body weight and animal survival rates were recorded over the course of the study. Skeletal muscle tissues were collected and used to measure NOX subunit mRNA, O2‾ levels and antioxidant enzymes.ResultsKey subunit components of NOX expression were elevated in skeletal muscle at 18 months, when sarcopenia was first evident. Increased superoxide dismutase 1 (SOD1) activity suggests an increase in O2‾ dismutation and this was further supported by elevated levels of hydrogen peroxide (H2O2) and decline in catalase and glutathione peroxidase (GPx) antioxidant protection in skeletal muscle at this time. NOX expression was also higher in skeletal muscle at 24 months, however this was coupled with elevated levels of O2‾ and a decline in SOD1 activity, compared to 6 and 12 months but was not associated with further loss of muscle mass.ConclusionsWhile the source of ROS in sarcopenic muscle remains unknown, this study provides evidence that the NOX enzyme could be involved in ROS production by regulating superoxide in ageing muscles. This study also suggests that H2O2 is the key ROS in the onset of sarcopenia and that the decline in antioxidant protection by catalase and GPx is indicative of antioxidant dysfunction and may therefore be a major contributing factor in the development or onset of sarcopenia. Furthermore, the changes in ROS and antioxidant activity after sarcopenia was first evident gives some evidence for a compensatory mechanism, in response to insult, in order to maintain muscle integrity.
Highlights
Sarcopenia is the progressive loss of skeletal muscle that contributes to the decline in physical function during aging
Skeletal muscle mass and muscle mass as ratio to body weight increased at 12 months of age compared to 6 months of age (p < 0.001, Table 1) and decreased at 18 (p < 0.001) and 24 (p < 0.001) months of age compared to 12 months (Table 1)
The time of significant change in skeletal muscle was at 18 months with an increase in NOX2 enzyme expression and levels of H2O2, antioxidant dysfunction and the onset of sarcopenia
Summary
Sarcopenia is the progressive loss of skeletal muscle that contributes to the decline in physical function during aging. A higher level of oxidative stress has been implicated in aging sarcopenia. The current study aims to determine if the higher level of oxidative stress is a result of increased superoxide (O2 ̅ ) production by the NADPH oxidase (NOX) enzyme or decrease in endogenous antioxidant enzyme protection. The progressive age-associated loss of muscle mass leads to significant weakness, frailty and decreased quality of life [6] NOX has been identified as the key source of O2 ̅ that contributes to cardiovascular aging [11] and other age-associated conditions such as diabetes [22], arthritis [23], cataracts [24], Alzheimer’s disease [25] and motorneuron dysfunction [10]
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