Philip J. Atherton's research while affiliated with University of Nottingham and other places

Publications (268)

Article
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Introduction: Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. However, the development of this association over time and the quantification of the strength of this association for individual BCAAs prior to T2DM diagnosis r...
Article
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Introduction Ageing skeletal muscles become both insulin resistant and atrophic. The hormone glucagon-like peptide 1 (GLP-1) facilitates postprandial glucose uptake as well as augmenting muscle perfusion - independent of insulin action. We thus hypothesized exogenous GLP-1 infusions would enhance muscle perfusion and positively impact glucose metab...
Article
Purpose: Resistance exercise training (RET) attenuates age-related muscle and strength loss (‘sarcopenia’). However, compared with machine-based RET, the efficacy of cost-effective, accessible elastic band RET (EB-RET) for muscle adaptive remodelling lacks supporting mechanistic evidence. Methods: 8 young (YM; 24 ± 4 yrs) and 8 older (OM; 68 ± 6 yr...
Article
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Abstract Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function when compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplor...
Article
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Ageing limits growth capacity of skeletal muscle (e.g. in response to resistance exercise), but the role of satellite cell (SC) function in driving this phenomenon is poorly defined. Younger (Y) (~ 23 years) and older (O) men (~ 69 years) (normal-weight BMI) underwent 6 weeks of unilateral resistance exercise training (RET). Muscle biopsies were ta...
Article
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The aim of the present study was to evaluate the effect of feeding fava bean (Vicia faba L.) protein (FBP) on resting and post-exercise myofibrillar fractional synthetic rate (myoFSR). In a parallel, double-blind, randomised control trial, sixteen young, healthy recreationally active adults (age = 25 (5) years, body mass = 70 (15) kg, stature = 1.7...
Article
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Short, intermittent episodes of disuse muscle atrophy (DMA) may have negative impact on age related muscle loss. There is evidence of variability in rate of DMA between muscles and over the duration of immobilization. As yet, this is poorly characterized. This review aims to establish and compare the time‐course of DMA in immobilized human lower li...
Article
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Resistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compar...
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Exercise training can induce adaptive changes to tendon tissue both structurally and mechanically; however, the underlying compositional changes that contribute to these alterations remain uncertain in humans, particularly in the context of the ageing tendon. The aims of the present study were to determine the molecular changes with ageing in patel...
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New findings: What is the central question of this study? We aimed to determine levels of bilateral knee extensor force accuracy and any subsequent alterations to central and/or peripheral motor unit features, following 4 weeks of unilateral force accuracy training. What is the main finding and its importance? In the trained limb only, knee extens...
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Low muscle mass and malnutrition are prevalent conditions among adults of all ages, with any body weight or body mass index, and with acute or chronic conditions, including COVID-19. This article synthesizes the latest research advancements in muscle health and malnutrition, and their impact on immune function, and clinical outcomes. We provide a t...
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Background: Reduced cardiorespiratory fitness (CRF) is an independent risk factor for dependency, cognitive impairment and premature mortality. High-intensity interval training (HIIT) is a proven time-efficient stimulus for improving both CRF and other facets of cardiometabolic health also known to decline with advancing age. However, the efficacy...
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Objectives This systematic review, meta-analysis, and meta-regression aimed to determine if increasing daily protein ingestion contributes to gaining lean mass (LM), muscle strength, and physical/functional test performance in healthy persons. Methods The present review was registered on PROSPERO - CRD42020159001. A systematic search in Medline, E...
Preprint
Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study...
Article
Background: Very Low-Calorie Diet (VLCD) is effective for rapid weight loss but is associated with lean mass (LM) loss. Resistance exercise training (RET) and high-intensity interval training (HIIT) are known to promote muscle hypertrophy or improvements in cardiopulmonary fitness (CPF) . We therefore explored the effects of VLCD with or without RE...
Article
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Muscle atrophy and sarcopenia (the term given to the age-related decline in muscle mass and function), influence an individuals risk of falls, frailty, functional decline, and, ultimately, impaired quality of life. Vitamin D deficiency (low serum levels of 25-hydroxyvitamin D (25(OH)D3)) has been reported to impair muscle strength and increase risk...
Article
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Background: We determined the short-term (i.e. 4 days) impacts of disuse atrophy in relation to muscle protein turnover [acute fasted-fed muscle protein synthesis (MPS)/muscle protein breakdown (MPB) and integrated MPS/estimated MPB]. Methods: Healthy men (N = 9, 22 ± 2 years, body mass index 24 ± 3 kg m-2 ) underwent 4 day unilateral leg immobi...
Poster
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Introduction: Skeletal muscle disuse atrophy (DA) through inactivity and immobilisation is not fully understood, and as such remains a major goal of global muscle biology science efforts. Nonetheless, remarkably not all leg muscles atrophy at the same rate or total degree despite similar anatomical roles/ proximity (1). Moreover, temporal aspects o...
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Therapeutic interventions aimed at enhancing blood flow may combat the postprandial vascular and metabolic dysfunction that manifests with chronological ageing. We compared the effects of acute curcumin (1000 mg) coupled with an oral nutritional supplement (ONS, 7.5 g protein, 24 g carbohydrate and 6 g fat) versus a placebo and ONS (control) on cer...
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Low muscle mass is prevalent among patients with cancer and a predictor of adverse clinical outcomes. To counteract muscle loss, β‐hydroxy β‐methylbutyrate (HMB) supplementation has been proposed as a potential therapy for older adults and various diseases states. This systematic review aimed to investigate the effects and safety of HMB supplementa...
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Background: The relative role of skeletal muscle mechano-transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6 weeks of resistance exercise training (RET) on muscle mass, f...
Article
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Validated diagnostics of skeletal muscle vitality could benefit clinical and basic science in terms of mechanistic insights and in determining the efficacy of interventions, e.g. exercise/pharmaceuticals/nutrients. We recently developed a Combined Oral Assessment of Muscle (COSIAM) that can be used to simultaneously quantify whole-body muscle mass...
Article
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A motor unit (MU) comprises the neuron cell body, its corresponding axon and each of the muscle fibres it innervates. Many studies highlight age‐related reductions in the number of MUs, yet the ability of a MU to undergo remodelling and to expand to rescue denervated muscle fibres is also a defining feature of MU plasticity. Remodelling of MUs invo...
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We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were r...
Article
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Abstract We performed a systematic review, meta‐analysis, and meta‐regression to determine if increasing daily protein ingestion contributes to gaining lean body mass (LBM), muscle strength, and physical/functional test performance in healthy subjects. A protocol for the present study was registered (PROSPERO, CRD42020159001), and a systematic sear...
Preprint
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Background Muscle force output during sustained submaximal isometric contractions fluctuates around an average value and is known to be influenced by variation in motor unit (MU) firing rates. MU firing rate variability seemingly reduces following exercise training interventions, however, much less is known with respect to peripheral MU properties....
Article
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Background and aims Elective surgery induces skeletal muscle wasting driven by an imbalance between muscle protein synthesis and breakdown. From examination of diverse stable isotope tracer techniques, the dynamic processes driving this imbalance are unclear. This meta-analysis aimed to elucidate the mechanistic driver(s) of postoperative protein c...
Article
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Aim: Despite males typically exhibiting greater muscle strength and fatigability than females, it remains unclear if there are sex-based differences in neuromuscular recruitment strategies e.g. recruitment and modulation of motor unit firing rate (MU FR) at normalised forces and during progressive increases in force. Methods: Twenty-nine healthy...
Article
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Purpose: Resistance training induces skeletal muscle hypertrophy via the summated effects of post-exercise elevations in myofibrillar protein synthesis (MyoPS) that persist for up to 48 h, although research in females is currently lacking. MyoPS is regulated by mTOR translocation and colocalization; however, the effects of resistance training on t...
Preprint
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Elevated plasma leucine, isoleucine and valine (BCAA) are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention. F...
Article
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Eccentric (ECC) and concentric (CON) contractions induce distinct muscle remodelling patterns that manifest early during exercise training, the causes of which remain unclear. We examined molecular signatures of early contraction mode-specific muscle adaptation via transcriptome-wide network and secretome analyses during 2 weeks of ECC- versus CON-...
Article
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Long-term exercise training has been considered as an effective strategy to counteract age-related hormonal declines and minimise muscle atrophy. However, human data relating circulating hormone levels with motor nerve function are scant. The aims of the study were to explore associations between circulating sex hormone levels and motor unit (MU) c...
Article
The objective of this study was to evaluate the association between frailty, evaluated by the Clinical Frailty Scale (CFS) and FRAIL scale, and C-terminal agrin fragment (CAF) levels with 3-month mortality following ST-segment elevation myocardial infarction (STEMI). This was a prospective observational study that included patients over the age of...
Preprint
Aim Despite men exhibiting greater muscle strength and fatigibility than women, it remains unclear if there are sex-based differences in muscle recruitment strategies e.g. motor unit (MU) recruitment and modulation of firing rate (FR) at normalised forces and during progressive increases in force. Methods Twenty-nine healthy male and thirty-one he...
Article
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This opinion paper presents a short review of the potential impact of protein on muscle anabolism in cancer, which is associated with better patient outcomes. Protein source is a topic of interest for patients and clinicians, partly due to recent emphasis on the supposed non-beneficial effect of proteins; therefore, misconceptions involving animal-...
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The influx of essential amino acids into skeletal muscle is primarily mediated by the large neutral amino acid transporter 1 (LAT1), which is dependent on the glutamine gradient generated by the sodium-dependent neutral amino acid transporter 2 (SNAT2). The protein expression and membrane localization of LAT1 may be influenced by amino acid ingesti...
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Postprandial macro- and microvascular blood flow and metabolic dysfunction manifest with advancing age, so vascular transmuting interventions are desirable. In this randomised, single-blind, placebo-controlled, crossover trial, we investigated the impact of the acute administration of green tea extract (GTE; containing ~500 mg epigallocatechin-3-ga...
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Protein ingestion is a potent stimulator of skeletal muscle protein synthesis (MPS). However, older adults demonstrate resistance to anabolic stimuli. Some evidence has demonstrated that a larger acute protein dose is required in older compared to younger adults to elicit the same synthetic response, suggesting that older adults should be consuming...
Article
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Impairments in muscle microvascular function are associated with the pathogenesis of sarcopenia and cardiovascular disease. High-intensity interval training (HIIT) is an intervention by which a myriad of beneficial skeletal muscle/cardiovascular adaptations have been reported across age, including capillarisation and improved endothelial function....
Conference Paper
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Introduction There is a growing body of evidence highlighting the importance of maintaining optimal serum vitamin D levels for sports performance, and studies have displayed that expression of the receptor by which vitamin D elicits its biological effects, the vitamin D receptor (VDR), is increased following a single bout of exercise whilst it decr...
Article
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Muscle disuse leads to a rapid decline in muscle mass, with reduced muscle protein synthesis (MPS) considered the primary physiological mechanism. Here, we employed a systems biology approach to uncover molecular networks and key molecular candidates that quantitatively link to the degree of muscle atrophy and/or extent of decline in MPS during sho...
Article
Acute hypoxia has previously been suggested to potentiate resistance training-induced hypertrophy by activating satellite cell-dependent myogenesis rather than an improvement in protein balance in human. Here, we tested this hypothesis after a 4-week hypoxic vs normoxic resistance training protocol. For that purpose, 19 physically active male subje...
Article
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Introduction: Serious health implications from having low levels of cardiorespiratory fitness (CRF) and being overweight in young adulthood are carried forward into later life. High-intensity interval training (HIIT) is a time-effective, potent stimulus for improving CRF and indices of cardiometabolic health. To date, few studies have investigated...
Article
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Background: Means-based analysis of maximal rate of oxygen consumption (VO2max) has traditionally been used as the exercise response indicator to assess the efficacy of endurance (END), high intensity interval (HIIT) and resistance exercise training (RET) for improving cardiorespiratory fitness and whole-body health. However, considerable heteroge...
Preprint
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Aim We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular markers. Methods Trained men (n=15, age: 23±3 y; training experience: 7±3 y) performed unilateral lower body training for 6 weeks (3x weekly), where single legs were assign...
Article
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Resistance exercise training (RET) is well-known to counteract negative age-related changes in both muscle and tendon tissue. Traditional RET consists of both concentric (CON) and eccentric (ECC) contractions; nevertheless, isolated ECC contractions are metabolically less demanding and, thus, may be more suitable for older populations. However, whe...
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We explored the views of older (≥65 years) past and potential volunteers in regard to participating in physiology research during the COVID-19 pandemic. Using an online questionnaire and focus groups, we found that past volunteers (n = 55) were more likely to take part in both acute (p < 0.05) and chronic (p < 0.05) physiology studies, compared wit...
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Background The assessment of muscle mass is a key determinant of the diagnosis of sarcopenia. We introduce for the first time an ultrasound imaging method for diagnosing sarcopenia based on changes in muscle geometric proportions. Methods Vastus lateralis muscle fascicle length (Lf) and thickness (Tm) were measured at 35% distal femur length by ul...
Article
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Introduction Assuming myokines underlie some of the health benefits of exercise, we hypothesised that ‘high responder trainer’ (HRT) rats would exhibit distinct myokine profiles to ‘low responder trainers’ (LRT), reflecting distinct health and adaptive traits. Methods Blood was collected from LRT and HRT (N=8) rats at baseline (BL), immediately (0...
Article
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Background: Declines in cardiorespiratory fitness (CRF) and fat-free mass (FFM) with age are linked to mortality, morbidity and poor quality of life. High-intensity interval training (HIIT) has been shown to improve CRF and FFM in many groups, but its efficacy in the very old, in whom comorbidities are present is undefined. We aimed to assess the...
Article
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Optimising approaches for measuring skeletal muscle mass and turnover that are widely applicable, minimally invasive and cost effective is crucial in furthering research into sarcopenia and cachexia. Traditional approaches for measurement of muscle protein turnover require infusion of expensive, sterile, isotopically labelled tracers which limits t...
Conference Paper
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Deuterium spectra of the human calf were obtained at natural abundance, at 3 T field strength. Two peaks with a chemical shift separation of 3.5 ppm were observed, corresponding to water and lipids, and their relaxation times T1 and T2* were measured using a transceive surface coil. Utilising the complex data to fit spectral lines, including indepe...
Conference Paper
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Muscle fatigue is characterised by a reduction in force output, with increases in force production partly mediated by adjustments in motor unit (MU) firing properties. Conflicting research has found MU firing rate (FR) to both increase and decrease following fatiguing exercise and this disparity may be influenced by contraction type. Using high den...
Article
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Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venou...
Article
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Background: Skeletal muscle atrophy manifests across numerous diseases; however, the extent of similarities/differences in causal mechanisms between atrophying conditions in unclear. Ageing and disuse represent two of the most prevalent and costly atrophic conditions, with resistance exercise training (RET) being the most effective lifestyle count...
Article
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Disuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant...
Article
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The development of safe and practical strategies to prevent weakening of bone tissue is vital, yet attempts to achieve this have been hindered by a lack of understanding of the short-term (days-weeks) physiology of bone collagen turnover. To address this, we have developed a method to quantify bone collagen synthesis in vivo, using deuterium oxide...