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BMC Geriatrics

, 13:104

Pathophysiology of musculoskeletal disorders


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.

KeywordsSarcopenia NADPH oxidase Superoxide Hydrogen Peroxide Antioxidants Electronic supplementary materialThe online version of this article doi:10.1186-1471-2318-13-104 contains supplementary material, which is available to authorized users.

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Autor: Melanie J Sullivan-Gunn - Paul A Lewandowski

Fuente: https://link.springer.com/

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