Anne McArdle

Anne McArdle
University of Liverpool | UoL · Department of Musculoskeletal Biology

About

271
Publications
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Publications

Publications (271)
Article
Full-text available
Background and aims: Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers. Methods: We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases f...
Article
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Research over almost 40 years has established that reactive oxygen species are generated at different sites in skeletal muscle and that the generation of these species is increased by various forms of exercise. Initially, this was thought to be potentially deleterious to skeletal muscle and other tissues, but more recent data have identified key ro...
Article
An increased presence of the oxidised DNA base lesion 8-oxo-7,8-dihydroguanine (8-oxoG) is seen in muscles of old mice. 8-oxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair pathway, a process proposed to lead to activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). We hyp...
Article
Skeletal muscle releases a number of signalling molecules, including immunomodulatory cytokines and chemokines which can act in an autocrine, paracrine and endocrine fashion. For example, neuromuscular integrity is dependent on efficient and appropriate signalling from muscle to nerve and vice versa and when such signalling fails then tissue deteri...
Article
Muscle mass is reduced with age and numerous studies have examined the potential role of global changes in proteostasis, through protein synthesis and/or degradation in the overall loss of muscle mass with age, although no consensus has been reached. We hypothesise that changes in expression, synthesis and degradation may be very different for indi...
Article
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Motor unit remodelling involving repeated denervation and re-innervation occurs throughout life. The efficiency of this process declines with age contributing to neuromuscular deficits. This study investigated differentially expressed genes (DEG) in muscle following peroneal nerve crush to model motor unit remodelling in C57BL/6 J mice. Muscle RNA...
Preprint
Whole body knock out of Cu, Zn superoxide dismutase1 (Sod1KO) results in accelerated, age-related loss of muscle mass and function associated with a breakdown of neuromuscular junctions (NMJ) similar to sarcopenia. In order to determine whether altered redox in motor neurons is integral to this phenotype, an inducible neuron specific deletion of So...
Article
Aging results in the progressive accumulation of senescent cells in tissues that display loss of proliferative capacity and acquire a senescence-associated secretory phenotype (SASP). The tumor suppressor, p16 INK4A , which slows the progression of the cell cycle, is highly expressed in most senescent cells and the removal of p16-expressing cells h...
Preprint
Full-text available
Aim Cruciate ligaments (CLs) of the knee joint are commonly injured following trauma or ageing. MicroRNAs (miRs) are potential therapeutic targets in musculoskeletal disorders. This study aimed to 1) identify if wild-stock house (WSH) mice are an appropriate model to study age-related changes of the knee joint and 2) investigate expression of miRs...
Article
Reactive oxygen species (ROS) are recognized as important signaling molecules in healthy skeletal muscle. Redox sensitive proteins can respond to intracellular changes in ROS by oxidation of reactive thiol groups on cysteine (Cys) residues. Exercise is known to induce the generation of superoxide and nitric oxide, resulting in the activation of sev...
Article
Reactive oxygen species (ROS) are recognised as important signalling molecules in healthy skeletal muscle. Redox sensitive proteins can respond to intracellular changes in ROS via reactive thiol groups on Cysteine (Cys) residues. While exercise is known to induce the generation of ROS that results in the activation of a number of transcription fact...
Article
Full-text available
Age-associated loss of muscle mass and function (sarcopenia) has a profound effect on the quality of life in the elderly. Our previous studies show that CuZnSOD deletion in mice (Sod1-/- mice) recapitulates sarcopenia phenotypes, including elevated oxidative stress and accelerated muscle atrophy, weakness, and disruption of neuromuscular junctions...
Preprint
Full-text available
Myalgic Encephalomyelitis (ME) /Chronic Fatigue Syndrome (CFS) is a severely debilitating and complex illness of uncertain aetiology, affecting the lives of millions and characterised by prolonged fatigue. The initiating factors and mechanisms leading to chronic debilitating muscle fatigue in ME/CFS are unknown and are complicated by the time requi...
Article
Full-text available
Skeletal muscle generates superoxide during contractions which is rapidly converted to H2O2. This molecule has been proposed to activate signalling pathways and transcription factors that regulate key adaptive responses to exercise but the concentration of H2O2 required to oxidise and activate key signalling proteins in vitro is much higher than th...
Article
Full-text available
Hydrogen peroxide appears to be the key reactive oxygen species involved in redox signalling, but comparisons of the low concentrations of hydrogen peroxide that are calculated to exist within cells with those previously shown to activate common signalling events in vitro indicate that direct oxidation of key thiol groups on “redox-sensitive” signa...
Article
Full-text available
To determine the role of denervation and motor unit turnover in the age-related increase in skeletal muscle oxidative stress, the hydrogen peroxide (H2O2) specific, genetically-encoded, fluorescent cyto-HyPer2 probe was expressed in mouse anterior tibialis (AT) muscle and compared with ex vivo measurements of mitochondrial oxidant generation. Crush...
Article
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Previous studies have shown a significant increase in the mitochondrial generation of hydrogen peroxide (H2O2) and other peroxides in recently denervated muscle fibers. The mechanisms for generation of these peroxides and how the muscle responds to these peroxides are not fully established. The aim of this work was to determine the effect of denerv...
Article
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 vario...
Article
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The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sh...
Article
Mice lacking Cu/Zn-superoxide dismutase (Sod1-/- or Sod1KO mice) show high levels of oxidative stress/damage and a 30% decrease in lifespan. The Sod1KO mice also show many phenotypes of accelerated aging with the loss of muscle mass and function being one of the most prominent aging phenotypes. Using various genetic models targeting the expression...
Article
The loss of muscle mass and weakness that accompanies ageing is a major contributor to physical frailty and loss of independence in older people and a failure of muscle to adapt to physiological stresses play important roles in theses deficits. The role of redox regulation in control of specific stress responses, including the generation of heat sh...
Article
Previous studies have shown increased mitochondrial generation of peroxides in denervated muscle fibers, but the role that peroxides play during denervation is still controversial. The Anterior Tibialis and Extensor Digitorum Longus muscles of wild type and Thy-1YFP mice were denervated by surgical removal of a small section of the peroneal nerve....
Article
Full-text available
Objective Severe vitamin D deficiency is a recognised cause of skeletal muscle fatigue and myopathy. The aim of this study was to examine whether chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with altered circulating vitamin D metabolites. Design Cohort study. Setting UK university hospital, recruiting from April 2014...
Article
Full-text available
The ability of reactive oxygen species (ROS) to cause molecular damage has meant that chronic oxidative stress has been mostly studied from the point of view of being a source of toxicity to the cell. However, the known duality of ROS molecules as both damaging agents and cellular redox signals implies another perspective in the study of sustained...
Article
Full-text available
Aims: Lack of CuZnSOD in homozygous knockout mice (Sod1-/-) leads to accelerated age-related muscle loss and weakness, but specific deletion of CuZnSOD in skeletal muscle(mSod1KO mice) or neurons (nSod1KO mice) resulted in only mild muscle functional deficits and failed to recapitulate the loss of mass and function observed in Sod1-/- mice. To dis...
Article
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Skeletal muscle aging is characterised by atrophy, a deficit in specific force generation, increased susceptibility to injury, and incomplete recovery after severe damage. The hypothesis that increased generation of Reactive Oxygen Species (ROS) in vivo plays a key role in the aging process has been extensively studied, but remains controversial. S...
Article
The circadian clock is an intrinsic timing mechanism which regulates most physiological processes within the body. Disruption of circadian rhythms has been identified as a risk factor for several chronic diseases with altered redox control. We investigated the hypothesis that NRF2, a master regulator of antioxidant defence, is a clock-controlled ge...
Article
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The accumulation of ‘senescent’ cells has long been proposed to act as an ageing mechanism. These cells display a radically altered transcriptome and degenerative phenotype compared with their growing counterparts. Tremendous progress has been made in recent years both in understanding the molecular mechanisms controlling entry into the senescent s...
Article
The loss of muscle mass and weakness that accompanies ageing is a major contributor to physical frailty and loss of independence in older people. A failure of muscle to adapt to physiological stresses such as exercise is seen with ageing and disruption of redox regulated processes and stress responses are recognized to play important roles in these...
Article
Full-text available
Disruption of neuromuscular junctions and denervation of some muscle fibres occurs in ageing skeletal muscle and contribute to loss of muscle mass and function. Aging is associated with mitochondrial dysfunction and loss of redox homeostasis potentially occurs through increased mitochondrial generation of reactive oxygen species (ROS). No specific...
Article
Full-text available
Frailty is a geriatric syndrome that is an important public health problem for the older adults living in the USA. Although several methods have been developed to measure frailty in humans, we have very little understanding of its etiology. Because the molecular basis of frailty is poorly understood, mouse models would be of great value in determin...
Conference Paper
Age-related loss of muscle mass and function greatly influences the quality of life of older people. Denervation, mitochondrial hydrogen peroxide (H202) production and elevated pro-inflammatory cytokines levels are thought to play a substantial role in this muscle dysfunction and to be key contributors to frailty in the elderly. A substantial body...
Conference Paper
Age-related loss of muscle mass and function greatly influences the quality of life of older people. Denervation, mitochondrial hydrogen peroxide (H202) production and elevated pro-inflammatory cytokines levels are thought to play a substantial role in this muscle dysfunction and to be key contributors to frailty in the elderly. A substantial body...
Conference Paper
Full-text available
Age-related loss of muscle mass and function greatly influences the quality of life of older people. Denervation, mitochondrial hydrogen peroxide (H202) production and elevated pro-inflammatory cytokines levels are thought to play a substantial role in this muscle dysfunction and to be key contributors to frailty in the elderly. A substantial body...
Article
With advancing age there is an increased occurrence of denervated skeletal muscle fibres, which is associated with morphological breakdown of neuromuscular junctions (NMJs). Dramatic changes in mitochondrial generation of hydrogen peroxide (H2O2) have been reported in skeletal muscle of rodents following experimental nerve transection¹. We hypothes...
Article
Age-related loss of muscle mass and function greatly influences the quality of life of older people. Denervation and increases in pro-inflammatory cytokines are proposed to play a substantial role in this muscle dysfunction. Full denervation of muscle of adult mice causes an increase in the rate of mitochondrial peroxide production¹ and data from o...
Conference Paper
Age-related loss of muscle mass and function greatly influences the quality of life of older people. Denervation and increases in pro-inflammatory cytokines are proposed to play a substantial role in this muscle dysfunction. Full denervation of muscle of adult mice causes an increase in the rate of mitochondrial peroxide production2 and data from o...
Article
Full-text available
Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmac...