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Elevated Hydrogen Peroxide and Decreased Catalase and Glutathione Peroxidase Protection Are Associated With Aging Sarcopenia

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Elevated Hydrogen Peroxide and Decreased Catalase and Glutathione Peroxidase Protection Are Associated With Aging Sarcopenia

Melanie J Sullivan-Gunn et al. BMC Geriatr.

Abstract

Background: 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.

Methods: Female 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.

Results: Key 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.

Conclusions: While 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.

Figures

Figure 1
Figure 1
Animal survival rates in the 18 and 24 month old age groups, expressed as a percentage of live animals for each group. Female BALB/c mice purchased at 9 months of age were assigned to the 18 month old group (n = 20) and 24 month old group (n = 24). Animal survival declined from approximately 14 months of age in both groups and continued to decline thereafter. A 60% decline in animal survival was observed in the 18 month old group (18 m/o), while a 50% decline in survival rate was observed the 24 month old group (24 m/o).
Figure 2
Figure 2
O2‾ levels in aging skeletal muscle, by histological DHE examination, values represent the area of fluorescence, above a specified threshold, expressed as a percentage of the total area of the muscle cross-section. The values represent the mean ± SEM. Statistically significant differences (P < 0.05) between groups are indicated by lower case letters, where a = 6 m/o, b = 12 m/o, c = 18 m/o and d = 24 m/o.
Figure 3
Figure 3
The protein levels of the NOX2 enzyme subunits and protein levels in aging skeletal muscle. A. Representative blots for NOX2, p40phox, p67phox and GAPDH. B. Graphical representation of protein concentration expressed as arbitrary units (AU) after normalisation for GAPDH concentration. The values represent the mean ± SEM. Statistically significant differences (P < 0.05) between groups are indicated by lower case letters, where a = 6 m/o, b = 12 m/o, c = 18 m/o and d = 24 m/o.

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