Aberrant redox signalling and stress response in age-related muscle decline: Role in inter- and intra-cellular signalling

Abstract

Age-associated frailty is predominantly due to loss of muscle mass and function. The loss of muscle mass is also associated with a greater loss of muscle strength, suggesting that the remaining muscle fibres are weaker than those of adults. The mechanisms by which muscle is lost with age are unclear, but in this review we aim to pull together various strands of evidence to explain how muscle contractions support proteostasis in non-muscle tissues, particularly focussed on the production and potential transfer of Heat Shock Proteins (HSPs) and how this may fail during ageing, Furthermore we will identify logical approaches, based on this hypothesis, by which muscle loss in ageing may be reduced. Skeletal muscle generates superoxide and nitric oxide at rest and this generation is increased by contractile activity. In adults, this increased generation of reactive oxygen and nitrogen species (RONS) activate redox-sensitive transcription factors such as nuclear factor κB (NFκB), activator protein-1 (AP1) and heat shock factor 1 (HSF1), resulting in increases in cytoprotective proteins such as the superoxide dismutases, catalase and heat shock proteins that prevent oxidative damage to tissues and facilitate remodelling and proteostasis in both an intra- and inter-cellular manner. During ageing, 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, increased oxidative damage and age-related dysfunction in skeletal muscle and potentially other tissues.

miR-455-3p Alleviates Hepatic Stellate Cell Activation and Liver Fibrosis by Suppressing HSF1 Expression

“…According to the bioinformatics analyses results, we found that HSF1 might be the direct targeting gene of miR-455-3p. HSF1 is the transcription factor primarily responsible for the transcriptional response of cells to physical and chemical stress, which assist in refolding or degrading damaged proteins 22, 23. HSF1 activation is accomplished at the post-translational modification and protein-protein interaction level 24 .…”

Are S-Klotho’s Maximal concentrations dependent on Exercise Intensity and Time in young adult males?

“…Previously it has been reported that oxidizing free radical species (ORS) are generated during aerobic bouts [13]. Skeletal muscles generate Super Oxide and Nitric Oxide which is increased by muscle contraction activity [14]. ROS is essential for skeletal muscle force generation, however, ROS in high values may reduce muscle contraction properties and thus, result in early exhaustion [15,16].…”

Exercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension

“…While there is still much to elucidate regarding the desensitization of redox circuitry, a modeling paper published in 2018 suggested that persistently elevated levels of stress or inflammation lead to “molecular habituation”, which leads to the desensitization of essential adaptive pathways [55]. Elevated levels of ROS (the signal) impair redox signaling by disrupting the initiation (via a sensor) of an adaptive response to the stress, thereby impairing the ability to functionally adapt to the stress [64,65]. Aged individuals have higher resting levels of ROS production, and they also have an impaired ability to acutely increase ROS to elicit an adaptive response [62,66].…”