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Review
. 2011 May 1;589(Pt 9):2139-45.
doi: 10.1113/jphysiol.2011.206623. Epub 2011 Feb 14.

Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species

Malcolm J Jackson  1 , Anne McArdle
Affiliations
Review

Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species

Malcolm J Jackson et al. J Physiol. .

Abstract

Skeletal muscle generates superoxide and nitric oxide at rest and this generation is increased by contractile activity. In young and adult animals and man, an increase in activities of these species and the secondary products derived from them (reactive oxygen species, ROS) stimulate redox-sensitive signalling pathways to modify the cellular content of cytoprotective regulatory proteins such as the superoxide dismutases, catalase and heat shock proteins that prevent oxidative damage to tissues. The mechanisms underlying these adaptive responses to contraction include activation of redox-sensitive transcription factors such as nuclear factor B (NFB), activator protein-1 (AP1) and heat shock factor 1 (HSF1). During ageing all tissues, including skeletal muscle, demonstrate an accumulation of oxidative damage that may contribute to loss of tissue homeostasis. The causes of this increased oxidative damage are uncertain, but substantial data now indicate that the ability of skeletal muscle from aged organisms to respond to an increase in ROS generation by increased expression of cytoprotective proteins through activation of redox-sensitive transcription factors is severely attenuated. This age-related lack of physiological adaptations to the ROS induced by contractile activity appears to contribute to a loss of ROS homeostasis and increased oxidative damage in skeletal muscle.

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Figures

Figure 1
Figure 1. Schematic representation of the processes by which ROS are generated in skeletal muscle in response to contractions and lead to the local oxidation of thiol (-SH) groups to activate redox-sensitive transcription factors including NFκB, AP1 and HSF1
A, the activated transcription factors migrate to the nucleus and bind to DNA in a locally reduced environment to stimulate transcription of cytoprotective proteins that act to restore ROS homeostasis. B, during ageing there is evidence for a chronic increase in release of hydrogen peroxide from mitochondria at rest and this is hypothesised to cause chronic oxidation of the redox-sensitive transcription factors at rest, but an oxidation of the nuclear environment that prevents DNA binding of the transcription factor. C, during contractile activity in the elderly there appears to be a failure of the ability to further activate transcription factors and increase the expression for cytoprotective proteins that may occur at several levels including a lack of activation of local ROS generation, a failure of further transcription factor activation and defective nuclear transcription factor binding.
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