Age-related changes in muscle architecture and metabolism in humans: The likely contribution of physical inactivity to age-related functional decline

Shur, N. F.; Creedon, L.; Skirrow, S.; Atherton, P. J.; MacDonald, I. A.; Lund, J.; Greenhaff, P. L.

doi:10.1016/j.arr.2021.101344

Creatine supplementation strategies aimed at acutely increasing and maintaining skeletal muscle total creatine content in healthy, young volunteers (2024)
Journal Article
Pittas, G., Miller, J., Laithwaite, D., & Greenhaff, P. (2024). Creatine supplementation strategies aimed at acutely increasing and maintaining skeletal muscle total creatine content in healthy, young volunteers. Translational Exercise Biomedicine, https://doi.org/10.1515/teb-2024-0032

Objectives: Insight regarding dietary creatine (Cr) supple-mentation strategies to acutely increase and maintain muscle total creatine (TCr) content is missing. Methods: Healthy, young, men ingested 4 × 5 g Cr/day (d) for 5d, followed by 5 g/d for 28... Read More about Creatine supplementation strategies aimed at acutely increasing and maintaining skeletal muscle total creatine content in healthy, young volunteers.

Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perception (2024)
Journal Article
McGing, J. J., Serres, S., Nicholas, R., Gupta, A., Radford, S. J., Nixon, A. V., Mallinson, J., Bradley, C., Bawden, S., Francis, S. T., Greenhaff, P. L., & Moran, G. W. (in press). Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perception. Journal of Crohn's and Colitis,

Background & Objective
IBD fatigue aetiology is poorly understood. This study quantified body composition and physical function alongside proton magnetic resonance imaging (1H MRI) and spectroscopy (31P MRS) measures of organ structure and function... Read More about Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perception.

DYNamic Assessment of Multi‐Organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19 (2024)
Journal Article
Gupta, A., Nicholas, R., McGing, J. J., Nixon, A. V., Mallinson, J. E., McKeever, T. M., Bradley, C. R., Piasecki, M., Cox, E. F., Bonnington, J., Lord, J. M., Brightling, C. E., Evans, R. A., Hall, I. P., Francis, S. T., Greenhaff, P. L., & Bolton, C. E. (2024). DYNamic Assessment of Multi‐Organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19. Experimental Physiology, 109(8), 1274-1291. https://doi.org/10.1113/ep091590

We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited... Read More about DYNamic Assessment of Multi‐Organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19.

The influence of immobility on muscle loss in older people with frailty and fragility fractures (2024)
Journal Article
Lunt, E. K., Gordon, A. L., Greenhaff, P. L., & Gladman, J. F. R. (2024). The influence of immobility on muscle loss in older people with frailty and fragility fractures. GeroScience, 46, 5473-5484. https://doi.org/10.1007/s11357-024-01177-1

This longitudinal study aimed to assess muscle morphological and functional changes in older patients admitted with fragility fractures managed by immobilisation of the affected limb for at least 6 weeks. Patients aged ≥ 70 hospitalised with non-weig... Read More about The influence of immobility on muscle loss in older people with frailty and fragility fractures.

Protein dose requirements to maximise skeletal muscle protein synthesis after repeated bouts of resistance exercise in young trained women (2023)
Journal Article
MALLINSON, J., WARDLE, S., O'LEARY, T., GREEVES, J., CEGIELSKI, J., BASS, J., BROOK, M., WILKINSON, D., SMITH, K., ATHERTON, P., & GREENHAFF, P. (2023). Protein dose requirements to maximise skeletal muscle protein synthesis after repeated bouts of resistance exercise in young trained women. Scandinavian Journal of Medicine and Science in Sports, 33(12), 2470-2481. https://doi.org/10.1111/sms.14506

Studies examining the effect of protein (PRO) feeding on post resistance exercise (RE) muscle protein synthesis (MPS) have primarily been performed in men, and little evidence is available regarding the quantity of PRO required to maximally stimulate... Read More about Protein dose requirements to maximise skeletal muscle protein synthesis after repeated bouts of resistance exercise in young trained women.

Feasibility of conducting a cohort randomized controlled trial assessing the effectiveness of a nurse-led package of care for knee pain (2023)
Journal Article
Fuller, A., Hall, M., Nomikos, P. A., Millar, B., Ogollah, R., Valdes, A., Greenhaff, P., das Nair, R., Doherty, M., Walsh, D. A., & Abhishek, A. (2024). Feasibility of conducting a cohort randomized controlled trial assessing the effectiveness of a nurse-led package of care for knee pain. Rheumatology, 63(6), 1582-1592. https://doi.org/10.1093/rheumatology/kead432

Objective
To evaluate the feasibility of conducting a cohort randomized controlled trial (RCT) of a nurse-led package of care for knee pain and determining a treatment sequence for use in a future trial.

Methods
This study was an open-label, thr... Read More about Feasibility of conducting a cohort randomized controlled trial assessing the effectiveness of a nurse-led package of care for knee pain.

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study (2023)
Journal Article
McAuley, H. J., Evans, R. A., Bolton, C. E., Brightling, C. E., Chalmers, J. D., Docherty, A. B., Elneima, O., Greenhaff, P. L., Gupta, A., Harris, V. C., Harrison, E. M., Ho, L.-P., Horsley, A., Houchen-Wolloff, L., Jolley, C. J., Leavy, O. C., Lone, N. I., Man, W. D.-C., Marks, M., Parekh, D., …Greening, N. J. (2023). Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study. eClinicalMedicine, 57, Article 101896. https://doi.org/10.1016/j.eclinm.2023.101896

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically d... Read More about Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.

The impact of physical inactivity on glucose homeostasis when diet is adjusted to maintain energy balance in healthy, young males (2023)
Journal Article
Trim, W. V., Walhin, J. P., Koumanov, F., Turner, J. E., Shur, N. F., Simpson, E. J., Macdonald, I. A., Greenhaff, P. L., & Thompson, D. (2023). The impact of physical inactivity on glucose homeostasis when diet is adjusted to maintain energy balance in healthy, young males. Clinical Nutrition, 42(4), 532-540. https://doi.org/10.1016/j.clnu.2023.02.006

Background & aims: It is unclear if dietary adjustments to maintain energy balance during reduced physical activity can offset inactivity-induced reductions in insulin sensitivity and glucose disposal to produce normal daily glucose concentrations an... Read More about The impact of physical inactivity on glucose homeostasis when diet is adjusted to maintain energy balance in healthy, young males.

Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men (2022)
Journal Article
Sayda, M. H., Abdul-Aziz, M. H., Gharahdaghi, N., Wilkinson, D. J., Greenhaff, P. L., Philips, B. E., Smith, K., Idris, I., & Atherton, P. J. (2022). Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men. Scientific Reports, 12, Article 19273. https://doi.org/10.1038/s41598-022-21814-z

Higher plasma leucine, isoleucine and valine (BCAA) concentrations 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-diab... Read More about Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men.

Prehabilitation: high-quality evidence is still required (2022)
Journal Article
Lobo, D. N., Skořepa, P., Gomez, D., & Greenhaff, P. L. (2022). Prehabilitation: high-quality evidence is still required. British Journal of Anaesthesia, https://doi.org/10.1016/j.bja.2022.09.016

Prehabilitation comprises multidisciplinary healthcare interventions, including exercise, nutritional optimisation, and psychological preparation, which aim to dampen the metabolic response to surgery, shorten the period of recovery, reduce complicat... Read More about Prehabilitation: high-quality evidence is still required.

Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization (2022)
Journal Article
Shur, N. F., Simpson, E. J., Crossland, H., Chivaka, P. K., Constantin, D., Cordon, S. M., Constantin-Teodosiu, D., Stephens, F. B., Lobo, D. N., Szewczyk, N., Narici, M., Prats, C., Macdonald, I. A., & Greenhaff, P. L. (2022). Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization. Journal of Cachexia, Sarcopenia and Muscle, 13(6), 2999-3013. https://doi.org/10.1002/jcsm.13075

Background: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers... Read More about Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.

The effects of elective abdominal surgery on protein turnover: A meta-analysis of stable isotope techniques to investigate postoperative catabolism (2022)
Journal Article
Jaconelli, M., Greenhaff, P. L., Atherton, P. J., Lobo, D. N., & Brook, M. S. (2022). The effects of elective abdominal surgery on protein turnover: A meta-analysis of stable isotope techniques to investigate postoperative catabolism. Clinical Nutrition, 41(3), 709-722. https://doi.org/10.1016/j.clnu.2022.01.023

Background & 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 ar... Read More about The effects of elective abdominal surgery on protein turnover: A meta-analysis of stable isotope techniques to investigate postoperative catabolism.

Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning (2021)
Journal Article
Alldritt, I., Greenhaff, P. L., & Wilkinson, D. J. (2021). Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning. International Journal of Molecular Sciences, 22(24), Article 13575. https://doi.org/10.3390/ijms222413575

Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy... Read More about Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning.

Feasibility RCT of neuromuscular electrical stimulation; an Intervention to Maintain and improve neuroMuscular function during periods of Immobility (IMMI): Protocol (2021)
Preprint / Working Paper
Gladman, J., Aloraibi, S., Greenhaff, P., Piasecki, M., Phillips, B., Atherton, P., Masud, T., Sahota, O., Logan, P., Booth, V., Robinson, K., Lunt, E., Godfrey, D., Caswell, A., Kerr, M., Ollivere, B., & Gordon, A. Feasibility RCT of neuromuscular electrical stimulation; an Intervention to Maintain and improve neuroMuscular function during periods of Immobility (IMMI): Protocol

East Midlands Research into Ageing Network (EMRAN) is a research collaboration across the East Midlands to facilitate collaborative applied clinical research into ageing and the care of older people. EMRAN was set up by NIHR CLAHRC East Midlands and... Read More about Feasibility RCT of neuromuscular electrical stimulation; an Intervention to Maintain and improve neuroMuscular function during periods of Immobility (IMMI): Protocol.

Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD (2021)
Journal Article
Latimer, L. E., Constantin-Teodosiu, D., Popat, B., Constantin, D., Houchen-Wolloff, L., Bolton, C. E., Steiner, M. C., & Greenhaff, P. L. (2022). Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD. European Respiratory Journal, 59(5), Article 2101507. https://doi.org/10.1183/13993003.01507-2021

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake (V'O2peak), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle-level dec... Read More about Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD.

The Regulatory Roles of PPARs in Skeletal Muscle Fuel Metabolism and Inflammation: Impact of PPAR Agonism on Muscle in Chronic Disease, Contraction and Sepsis (2021)
Journal Article
Crossland, H., Constantin-Teodosiu, D., & Greenhaff, P. L. (2021). The Regulatory Roles of PPARs in Skeletal Muscle Fuel Metabolism and Inflammation: Impact of PPAR Agonism on Muscle in Chronic Disease, Contraction and Sepsis. International Journal of Molecular Sciences, 22(18), 1-13. https://doi.org/10.3390/ijms22189775

The peroxisome proliferator-activated receptor (PPAR) family of transcription factors has been demonstrated to play critical roles in regulating fuel selection, energy expenditure and inflammation in skeletal muscle and other tissues. Activation of P... Read More about The Regulatory Roles of PPARs in Skeletal Muscle Fuel Metabolism and Inflammation: Impact of PPAR Agonism on Muscle in Chronic Disease, Contraction and Sepsis.

Review article: The aetiology of fatigue in inflammatory bowel disease and potential therapeutic management strategies (2021)
Journal Article
McGing, J. J., Radford, S. J., Francis, S. T., Serres, S., Greenhaff, P. L., & Moran, G. W. (2021). Review article: The aetiology of fatigue in inflammatory bowel disease and potential therapeutic management strategies. Alimentary Pharmacology and Therapeutics, 54(4), 368-387. https://doi.org/10.1111/apt.16465

Background: Fatigue is the inability to achieve or maintain an expected work output resulting from central or peripheral mechanisms. The prevalence of inflammatory bowel disease (IBD) fatigue can reach 86% in active disease, persisting in 50%-52% of... Read More about Review article: The aetiology of fatigue in inflammatory bowel disease and potential therapeutic management strategies.

Muscle and tendon adaptations to moderate load eccentric vs. concentric resistance exercise in young and older males (2021)
Journal Article
Quinlan, J. I., Franchi, M. V., Gharahdaghi, N., Badiali, F., Francis, S., Hale, A., Phillips, B. E., Szewczyk, N., Greenhaff, P. L., Smith, K., Maganaris, C., Atherton, P. J., & Narici, M. V. (2021). Muscle and tendon adaptations to moderate load eccentric vs. concentric resistance exercise in young and older males. GeroScience, 43(4), 1567-1584. https://doi.org/10.1007/s11357-021-00396-0

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... Read More about Muscle and tendon adaptations to moderate load eccentric vs. concentric resistance exercise in young and older males.

Potential role for pyruvate kinase M2 in the regulation of murine cardiac glycolytic flux during in vivo chronic hypoxia (2021)
Journal Article
Handzlik, M. K., Tooth, D. J., Constantin-Teodosiu, D., Greenhaff, P. L., & Cole, M. A. (2021). Potential role for pyruvate kinase M2 in the regulation of murine cardiac glycolytic flux during in vivo chronic hypoxia. Bioscience Reports, 41(6), Article BSR20203170. https://doi.org/10.1042/bsr20203170

Carbohydrate metabolism in heart failure shares similarities to that following hypoxic exposure, and is thought to maintain energy homeostasis in the face of reduced O2 availability. As part of these in vivo adaptations during sustained hypoxia, the... Read More about Potential role for pyruvate kinase M2 in the regulation of murine cardiac glycolytic flux during in vivo chronic hypoxia.

Age-related changes in muscle architecture and metabolism in humans: The likely contribution of physical inactivity to age-related functional decline (2021)
Journal Article
Shur, N. F., Creedon, L., Skirrow, S., Atherton, P. J., MacDonald, I. A., Lund, J., & Greenhaff, P. L. (2021). Age-related changes in muscle architecture and metabolism in humans: The likely contribution of physical inactivity to age-related functional decline. Ageing Research Reviews, 68, Article 101344. https://doi.org/10.1016/j.arr.2021.101344

In the United Kingdom (UK), it is projected that by 2035 people aged >65 years will make up 23 % of the population, with those aged >85 years accounting for 5% of the total population. Ageing is associated with progressive changes in muscle metabolis... Read More about Age-related changes in muscle architecture and metabolism in humans: The likely contribution of physical inactivity to age-related functional decline.

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