Aaron Russell

• PhD
• Professor at Deakin University

Exercise training is considered a non-pharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with Amyotrophic Lateral Sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-r...

Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance an...

Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance an...

Loss of function mutations in the gene encoding dystrophin elicits a hypersensitive fear response in mice and humans. In the dystrophin-deficient mdx mouse, this behaviour is partially protected by oestrogen, but the mechanistic basis for this protection is unknown. Here, we show that female mdx mice remain normotensive during restraint stress comp...

Objective Skeletal muscle oxidative capacity is central to physical activity, exercise capacity and whole-body metabolism. The three estrogen related receptors (ERRs) are regulators of oxidative metabolism in many cell types, yet their roles in skeletal muscle remain unclear. The main aim of this study was to compare the relative contributions of E...

Resistance-based blood flow restriction training (BFRT) improves skeletal muscle strength and size. Unlike heavy-load resistance training (HLRT), there is debate as to whether strength adaptations following BFRT interventions can be primarily attributed to concurrent muscle hypertrophy, as the magnitude of hypertrophy is often minor. The present st...

Mutation to the gene encoding dystrophin can cause Duchenne muscular dystrophy (DMD) and increase the sensitivity to stress in vertebrate species, including the mdx mouse model of DMD. Behavioral stressors can exacerbate some dystrophinopathy phenotypes of mdx skeletal muscle and cause hypotension‐induced death. However, we have discovered that a s...

Skeletal muscle dysfunction may contribute to the progression and severity of amyotrophic lateral sclerosis (ALS). In the present study, we characterized the skeletal muscle pathophysiology in an inducible transgenic mouse model (rNLS8) that develops a TAR-DNA binding protein (TDP-43) proteinopathy and ALS-like neuropathology and disease progressio...

New findings: What is the central question of this study? Striated Muscle activator of Rho signalling (STARS) is an actin-binding protein that regulates transcriptional pathways controlling muscle function, growth and myogenesis; processes impaired in dystrophic muscle. Regulation of the STARS pathway in Duchenne muscular dystrophy (DMD is unknown...

Skeletal muscle is sensitive to environmental cues that are first present in utero. Maternal over-nutrition is a model of impaired muscle development leading to structural and metabolic dysfunction in adult life. In this study, we investigated the effect of an obesogenic maternal environment on growth and post-natal myogenesis in the offspring. Mal...

Allsopp, GL, Hoffmann, SM, Feros, SA, Pasco, JA, Russell, AP, and Wright, CR. The effect of normobaric hypoxia on resistance training adaptations in older adults. J Strength Cond Res 36(8): 2306-2312, 2022-The effect of normobaric hypoxia on strength, body composition, and cardiovascular fitness was investigated after a resistance training interven...

MicroRNAs (miRNAs) are important regulators of cellular homeostasis and exert their effect by directly controlling protein expression. We have previously reported an age-dependent, negative association between microRNA-99b (miR-99b-5p) expression and muscle protein synthesis in human muscle in vivo. Here we investigated the role of miR-99b-5p as a...

The combinations of food consumed together (dietary patterns) may have a greater influence on health than nutrients or food groups consumed independently. This study investigated the relationship between dietary patterns, body composition and metabolic biomarkers of premenopausal New Zealand women from three ethnic groups. In total, 408 New Zealand...

Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, involves the rapid deterioration of motor neurons resulting in severe muscle atrophy and respiratory insufficiency. It is considered a “multisystemic” disease with many potential mechanisms responsible for its pathology. Currently, there is no cure for ALS. Exercise training is...

Abstract Lipid mediators including classical arachidonic acid‐derived eicosanoids (e.g. prostaglandins and leukotrienes) and more recently identified specialized pro‐resolving‐mediator metabolites of the omega‐3 fatty acids play essential roles in initiation, self‐limitation, and active resolution of acute inflammatory responses. In this study, we...

Background: MicroRNAs (miRNAs) are increasingly being identified as modulatory molecules for physiological and pathological processes in muscle. Here, we investigated whether miRNAs influenced the expression of the stress-responsive gene N-myc downstream-regulated gene 2 (Ndrg2) in skeletal muscle cells through the targeted degradation or translat...

Objective Endurance exercise training remodels skeletal muscle, leading to increased mitochondrial content and oxidative capacity. How exercise entrains skeletal muscle signaling pathways to induce adaptive responses remains unclear. In past studies, we identified Perm1 (PGC-1 and ERR induced regulator, muscle 1) as an exercise-induced gene and sho...

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively affect skeletal muscle. This can result in a loss of muscle mass (atrophy) and/or loss of muscle quality (reduced force per unit of muscle mass), both of which are prevalent in chronic disease, m...

Background MicroRNAs are small, non‐coding RNAs that regulate gene expression at the post‐transcriptional level. Epidemiological studies have identified association between circulating miRNAs and specific health outcomes such as cognitive function, muscle development, and cardiovascular disease. While some evidence exists to suggest that diet may m...

The transcriptional coactivators peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PGC-1β are positive regulators of skeletal muscle mass and energy metabolism; however, whether they influence muscle growth and metabolic adaptations via increased protein synthesis is not clear. This study revealed PGC-1α or PGC-1β overexpress...

The forkhead box O3 (FOXO3, or FKHRL1) protein is a member of the FOXO subclass of transcription factors. FOXO proteins were originally identified as regulators of insulin-related genes; however, they are now established regulators of genes involved in vital biological processes, including substrate metabolism, protein turnover, cell survival, and...

Measurement of rodent skeletal muscle contractile function is a useful tool that can be used to track disease progression as well as efficacy of therapeutic intervention. We describe here the non-invasive, in vivo assessment of the dorsiflexor muscles that can be repeated over time in the same mouse.

PurposeWe examined the concurrent characteristics of the remote development of strength and cross-sectional area (CSA) of upper body skeletal muscle in response to lower body resistance training performed with an applied blood flow restriction (BFR). Methods Males allocated to an experimental BFR group (EXP; n = 12) or a non-BFR control group (CON;...

Purpose: Telomere length is a biomarker of cellular ageing, with longer telomeres associated with longevity and reduced risk of chronic disease in older age. Consumption of a healthy diet may contribute to longevity via its impact on cellular ageing, but studies on diet and telomere length to date have been limited and their findings equivocal. Th...

Introduction: The pathology of amyotrophic lateral sclerosis (ALS) is associated with impaired RNA processing and miRNA dysregulation. Here we investigate the regulation of the members of the miRNA biogenesis pathways and total miRNA levels at different stages of the disease. Methods: Muscle, brain and spinal cord tissue were obtained from pre-s...

Granulocyte colony-stimulating factor (G-CSF) was originally discovered in the context of hematopoiesis. However, the identification of the G-CSF receptor (G-CSFR) being expressed outside the hematopoietic system has revealed wider roles for G-CSF, particularly in tissue repair and regeneration. Skeletal muscle damage, including that following stre...

Key points: Cardiac hypertrophy following endurance-training is thought to be due to hypertrophy of existing cardiomyocytes. The benefits of endurance exercise on cardiac hypertrophy are generally thought to be short-lived and regress to sedentary levels within a few weeks of stopping endurance training. We have now established that cardiomyocyte...

[This corrects the article on p. 170 in vol. 5, PMID: 24822049.].

Objective: Provocative evidence promotes the beneficial role of exercise in prostate cancer survivorship as a low-toxicity adjuvant, synergistic and targeted medicine that can be combined with standard cancer therapies to improve patient outcomes. Recently, the INTERVAL-MCRPC trial launched to examine exercise and overall survival in men with metas...

Members of the peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1) family of proteins regulate mitochondrial biogenesis and function in the cell. PGC-1α and PGC-1β are highly expressed in skeletal muscle where they partner with numerous transcription factors to regulate energy metabolism. PGC-1α and PGC-1β not only contro...

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by polyglutamine expansion in the androgen receptor (AR) and characterized by the loss of lower motor neurons. Here we investigated pathological processes occurring in muscle biopsy specimens derived from SBMA patients and, as controls, age-matched healthy subjects and pat...

Background MiRNAs are essential regulators of skeletal muscle development and homeostasis. To date, the role and regulation of miRNAs in myogenesis have been mostly studied in tissue culture and during embryogenesis. However, little information relating to miRNA regulation during early post-natal skeletal muscle growth in mammals is available. Usin...

Individual responses to transcranial direct current stimulation (tDCS) are varied and therefore potentially limit its application. There is evidence that this variability is related to the contributions of Indirect waves (I-waves) recruited in the cortex. The latency of motor-evoked potentials (MEPs) can be measured through transcranial magnetic st...

Aim: The striated muscle activator of Rho signalling (STARS) is a muscle-specific actin-binding protein. The STARS signalling pathway is activated by resistance exercise and is anticipated to play a role in signal mechanotransduction. Animal studies have reported a negative regulation of STARS signalling with age, but such regulation has not been...

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal motor neuron disorder. It results in progressive degeneration and death of upper and lower motor neurons, protein aggregation, severe muscle atrophy and respiratory insufficiency. Median survival with ALS is between 2 and 5 years from the onset of symptoms. AL...

Purpose: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the m...

We compared the effects of concurrent exercise, incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT), on mTORC1 signalling and microRNA expression in skeletal muscle, relative to resistance exercise (RE) alone. Eight males (mean ± SD: age, 27 ± 4 y; "V" O2peak, 45.7 ± 9 ml•kg-1•min-1) performe...

Purpose: We investigated if oral ingestion of ibuprofen influenced leucocyte recruitment and infiltration following an acute bout of traditional resistance exercise Methods: Sixteen male subjects were divided into two groups that received the maximum over-the-counter dose of ibuprofen (1200mg d⁻¹) or a similarly administered placebo following lower...

Background: Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of...

(A) STARS mRNA levels following STARS overexpression in C2C12 myoblasts. (B) STARS protein levels following STARS overexpression in C2C12 myoblasts. (C) 2H Enrichment expressed as a percentage of EM1 following deuterium incorporation assay. (D) Absorbance measured at 485 nm following a cytotoxicity assay in C2C12 myoblasts. (E) Absorbance measured...

Full western blot images of all immunoblot pictures presented in the manuscript.

Aim/hypothesis: Skeletal muscle insulin resistance and oxidative stress are characteristic metabolic disturbances in people with type 2 diabetes. Studies in insulin resistant rodents show an improvement in skeletal muscle insulin sensitivity and oxidative stress following antioxidant supplementation. We therefore investigated the potential amelior...

Regular exercise stimulates numerous structural, metabolic, and morphological adaptations in skeletal muscle. These adaptations are vital to maintain human health over the life span. Exercise is therefore seen as a primary intervention to reduce the risk of chronic disease. Advances in molecular biology, biochemistry, and bioinformatics, combined w...

Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes...

Body mass index (BMI) (kg/m(2)) is used internationally to assess body mass or adiposity. However, BMI does not discriminate body fat content or distribution and may vary among ethnicities. Many women with normal BMI are considered healthy, but may have an unidentified "hidden fat" profile associated with higher metabolic disease risk. If only BMI...

Background: It is clear that reactive oxygen species (ROS) produced during skeletal muscle contraction have a regulatory role in skeletal muscle adaptation to endurance exercise. However, there is much controversy in the literature regarding whether attenuation of ROS by antioxidant supplementation can prevent these cellular adaptations. Therefore...

Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole-body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age-rel...

In small mammals brown adipose tissue (BAT) plays a predominant role in regulating energy expenditure (EE) via adaptive thermogenesis. New-born babies require BAT to control their body temperature, however its relevance in adults has been questioned. Active BAT has recently been observed in adult humans, albeit in much lower relative quantities tha...

In the last 50 years, the number of individuals over the age of 65 years in the United States has doubled. A further doubling is expected by 2030, dramatically increasing the number of adults at risk of sarcopenia, a condition characterized by an age-related loss of muscle mass with an associated reduction in physical function. A reduction in muscl...

The function of the stress-responsive N-myc downstream-regulated gene 2 (NDRG2) in the control of myoblast growth, and the amino acids contributing to its function, are not well characterized. Here, we investigated the effect of increased NDRG2 levels on the proliferation, differentiation and apoptosis in skeletal muscle cells under basal and stres...

The cytokine granulocyte colony-stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate hematopoietic stem cell mobilization, myelopoiesis, and the production and activation of neutrophils. In response to exercise-induced muscle damage, G-CSF is increased in circulation and G-CSFR has recently been identified in skeletal muscle cells...

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between stati...

Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specif...

Sprint exercise and hypoxic stimulus during exercise are potent factors affecting hormonal and metabolic responses. However, the effects of different hypoxic levels on hormonal and metabolic responses during sprint exercise are not known. Here, we examined the effect of different hypoxic conditions on hormonal and metabolic responses during sprint...

Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to enhance skeletal muscle recovery following injury and increases muscle function in the context of neuromuscular disease in rodent models. However, understanding of the underlying mechanisms used by G-CSF to mediate these functions remains poor. G-CSF acts on responsive cells thr...

Body mass index (BMI) (kg/m(2)) is used internationally to assess body mass or adiposity. However, BMI does not discriminate body fat content or distribution and may vary among ethnicities. Many women with normal BMI are considered healthy, but may have an unidentified "hidden fat" profile associated with higher metabolic disease risk. If only BMI...

BACKGROUND: In small mammals brown adipose tissue (BAT) plays a predominant role in regulating energy expenditure (EE) via adaptive thermogenesis. New-born babies require BAT to control their body temperature, however its relevance in adults has been questioned. Active BAT has recently been observed in adult humans, albeit in much lower relative qu...

Over the course of ageing there is a natural and progressive loss of skeletal muscle mass. The onset and progression of age-related muscle wasting is associated with an attenuated activation of Akt-mTOR signalling and muscle protein synthesis in response to anabolic stimuli such as resistance exercise. MicroRNAs (miRNAs) are novel and important pos...

Introduction: The contribution of reduced testosterone levels to tail suspension (TS)-induced muscle atrophy remains equivocal. The molecular mechanism by which testosterone regulates muscle mass during TS has not been investigated. Methods: Effects of TS on serum testosterone levels, muscle mass, and expression of muscle atrophy- and hypertroph...

The cytokine granulocyte-colony stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate haematopoietic stem cell mobilization, myelopoiesis and the production and activation of neutrophils. G-CSF is increased in the circulation in response to exercise-induced muscle damage and the G-CSF receptor (G-CSFR) has recently been identified...

Resistance exercise triggers a subclinical inflammatory response that plays a pivotal role in skeletal muscle regeneration. Nuclear factor-κB (NF-κB) is a stress signalling transcription factor that regulates acute and chronic states of inflammation. The classical NF-κB pathway regulates the early activation of post-exercise inflammation; however t...

Antioxidant vitamin C (VC) supplementation is of potential clinical benefit to individuals with skeletal muscle oxidative stress. However there is a paucity of data reporting on the bioavailability of high dose oral VC in human skeletal muscle. We aimed to establish the time-course accumulation of VC in skeletal muscle and plasma during high dose V...

As a transcriptional coactivator, PGC-1α contributes to the regulation of a broad range of metabolic processes in skeletal muscle health and disease; however, there is limited information about the genes it transcriptionally regulates. To identify new potential gene targets of PGC-1α regulation, mouse C2C12 myotubes were screened by microarray anal...

Intramuscular creatine plays a crucial role in maintaining skeletal muscle energy homeostasis, and its entry into the cell is dependent upon the sodium chloride dependent Creatine Transporter (CrT; Slc6a8). CrT activity is regulated by a number of factors including extra- and intracellular creatine concentrations, hormones, changes in sodium concen...

The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8) knockout mice (CrT-/y) actually contained creatine (Cr) and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT-/y and wild type (CrT+/y) mice were analyzed for ATP, Cr, Cr...

Knowledge on the effects of divergent exercise on ostensibly protein degradation pathways may be valuable for counteracting muscle wasting and for understanding muscle remodelling. This study examined mRNA and/or protein levels of molecular markers of the ubiquitin proteasome pathway (UPP), including FBXO32 (atrogin-1), MURF-1, FBXO40, FOXO1 and FO...

Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol and is increased during energy stress such as exercise. Adipose triglyceride lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle lipolysis. Hence, we hypothesized that n...

Hypoxia is an important modulator of endurance exercise-induced oxidative adaptations in skeletal muscle. However, whether hypoxia affects resistance exercise-induced muscle adaptations remains unknown. Here, we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resista...

Granulocyte-colony stimulating factor (G-CSF) increases recovery of rodent skeletal muscles after injury, and increases muscle function in rodent models of neuromuscular disease. However, the mechanisms by which G-CSF mediates these effects are poorly understood. G-CSF acts by binding to the membrane spanning G-CSFR and activating multiple intracel...

Skeletal muscles contain several subtypes of myofibers that differ in contractile and metabolic properties. Transcriptional control of fiber-type specification and adaptation has been intensively investigated over the past several decades. Recently, microRNA (miRNA)-mediated posttranscriptional gene regulation has attracted increasing attention. Mi...

The role and regulation of the pleiotropic cytokine erythropoietin (EPO) in skeletal muscle are controversial. EPO exerts its effects by binding its specific receptor (EPO-R), which activates intracellular signaling and gene transcription in response to internal and external stress signals. EPO is suggested to play a direct role in myogenesis via t...

During the last decade, the striated muscle activator of Rho signaling (STARS), a muscle-specific protein, has been proposed to play an increasingly important role in skeletal muscle growth, metabolism, regeneration and stress adaptation. STARS influences actin dynamics and, as a consequence, regulates the myocardin-related transcription factor A/s...

Phenotypic screening is making a comeback in drug discovery as the maturation of chemical proteomics methods has facilitated target identification for bioactive small molecules. A limitation of these approaches is that time-consuming genetic methods or other means are often required to determine the biologically relevant target (or targets) from am...

Skeletal muscle atrophy is a critical component of the ageing process. Age-related muscle wasting is due to disrupted muscle protein turnover, a process mediated in part by the ubiquitin proteasome pathway (UPP). Additionally, older subjects have been observed to have an attenuated anabolic response, at both the molecular and physiological levels,...