Molecular Exercise Physiology Group
Contacts
Dr Arimantas Lionikas
Personal web page |
Dr Stuart Gray
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Dr Henning Wackerhage
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Dr Aivaras Ratkevicius
Personal web page |
Human beings have evolved as an exercise-dependent species and many diseases are caused by a sedentary life style often coupled with poor nutrition. As a consequence exercise is an important tool for preventing and treating disease. Sport and exercise also contribute significantly to the national economy from football clubs via gyms and sports good producers.
Exercise physiology aims at understanding the body's reaction to exercise and sport. It has now moved from whole body measurements to investigations at the molecular level. Thus molecular biology techniques are essential to address key questions such as 'why do muscles grow after exercise?' or 'what genetic variations determine athletic performance?'. We use the term 'molecular exercise physiology' to describe this new field and define it as follows:
"Molecular exercise physiology is the study of genetics and signal transduction in relation to exercise. Molecular exercise physiologists aim to identify the genetic determinants of human performance on a molecular level and characterize the mechanisms responsible for the adaptation of cells and organs to exercise" (Spurway and Wackerhage, 2006).
Molecular exercise physiology has achieved a significant progress in understand the mechanisms controlling muscle fibre type composition which is important for speed, power and, as our studies show, energetic efficiency of skeletal muscles (Nakagawa et al. 2005). Interestingly, spinal cord injury leads to remarkable changes in muscle fibre type composition of the affected skeletal muscles (Hartkopp et al. 1999). Our studies show that ERK1/2 and calcineurin pathways play important role in the expression of fibre type markers such as myosin heavy chain isoforms and enzymes (Higginson et al. 2002).
Our PhD student Phil Atherton (Atherton et al. 2005) has used an isolated muscle model in order to use electrical stimulation to mimic endurance and resistance exercise. We found that resistance exercise-like stimulation, but not endurance exercise-like stimulation, increased protein synthesis and activated the mTOR signalling cascade. In contrast, endurance exercise-like stimulation but not resistance exercise-like stimulation activated AMPK signalling and induced uncoupling protein 3, a marker for adaptation to endurance exercise.
We also have experience in cell signalling studies on biopsies from human skeletal muscles which have been obtained by Prof. Mike Rennie's team. In a study conducted by Dr. Dan Cuthbertson (now University of Liverpool), we have demonstrated the dose-response of human skeletal muscle to amino acid ingestion and that subjects in their 70s have a similar basal rate but respond with a much reduced increase in protein synthesis to amino acid stimulation. We have shown that signalling proteins in the mTOR cascade also less phosphorylated in response to amino acid stimulation than in young muscle, suggesting that the defect is upstream of mTOR. Also, the concentrations of many growth regulating signalling proteins are significantly changed in old skeletal muscle which may be a mechanism contributing to sarcopenia.
Based on others and our research we have produced a 'signalling map' that gives an overview over the signalling pathways that have been linked to the regulation of skeletal muscle size and other phenotype aspects such as fibre type (Powerpoint).
The major goals of our current research are:
- To understand how the myostatin-Smad pathway interacts with other signalling pathways to control skeletal muscle mass in response to exercise and other stimuli.
- To develop strategies to inhibit the myostatin-Smad pathway in order to promote skeletal muscle growth.
- To investigate the mechanisms that are responsible for muscle growth adaptation in response to strength/resistance training and fatigue resistance adaptation to endurance training.
- To identify biochemical, genetic and imaging biomarkers of sarcopenia (i.e. the muscle wasting that occurs with normal ageing), other muscle wasting conditions and muscle size.
Funding
- NHS endowment: Interaction between IGF-1-mTOR and myostatin-Smad pathways;
- BBSRC: Sarcopenia and resistance training (led by Prof. Mike Rennie);
- TMRC (Translational Medicine Research Collaboration between Wyeth Inc. and Scotish universities): (1) identification of serum biomarkers for sarcopenia; focus on myostatin-related serum growth mediators, (2) imaging markers for muscle function (Led by Prof. Richard M. Aspden).
- EPSRC: Novel MRI method to measure protein concentration of muscle (led by Prof. David Lurie).
Collaborators
- Prof. Richard Aspden, University of Aberdeen, UK
- Dr. Richard Jaspers, Free University, Amsterdam, Netherlands
- Dr. Arimantas Lionikas, The Pennsylvania State University, USA
- Prof. David Lurie, University of Aberdeen, UK
- Prof. Mike Rennie, University of Nottingham, UK
- Prof. David Reid, University of Aberdeen, UK
Development of Molecular Exercise Physiology in UK and abroad
Henning Wackerhage is the convener of a Molecular Exercise Physiology interest group within the British Association for Sport and Exercise Sciences (BASES). He has initiated and co-authors a BASES position stand on 'Genetic Research and Testing in Sport and Exercise Science' (weblink) and he has organised two (Dundee, Aberdeen) and contributed to one (Oxford) BASES workshop in Molecular Exercise Physiology. He is also author of a book "Genetics and Molecular Biology of Muscle Adaptation" which has been rated 10 out of 10 in 'The Sport and Exercise Scientist' which is the BASES society journal. Last but not least he is programme coordinator for a MSc in Molecular Exercise Physiology. Aivaras Ratkevicius was invited speaker in two seminars on Molecular Exercise Physiology organised by Institute of Cardiology, Kaunas University of Medicine (Lithuania) in 2006 and 2007.
Books
Spurway NC & Wackerhage H (2006). Genetics and molecular biology of muscle adaptation Elsevier/Churchill Livingstone, Edinburgh.
Key original papers
Atherton PJ, Babraj J, Smith K, Singh J, Rennie MJ, & Wackerhage H (2005). Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 19, 786-788.
Cuthbertson DJ, Babraj JA, Mustard KJ, Towler MC, Green KA, Wackerhage H, Leese GP, Baar K, Thomason-Hughes M, Sutherland C, Hardie DG, & Rennie MJ (2007b). 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes 56, 2078-2084.
Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, Wackerhage H, Taylor PM, & Rennie MJ (2005). Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J 19, 422-424.
Hartkopp A, Andersen JL, Harridge SD, Crone C, Gruschy-Knudsen T, Kjaer M, Masao M, Ratkevicius A, Quistorff B, Zhou S, & Biering-Sorensen F (1999). High expression of MHC I in the tibialis anterior muscle of a paraplegic patient. Muscle Nerve 22, 1731-1737.
Higginson J, Wackerhage H, Woods N, Schjerling P, Ratkevicius A, Grunnet N, & Quistorff B (2002). Blockades of mitogen-activated protein kinase and calcineurin both change fibre-type markers in skeletal muscle culture. Pflugers Arch 445, 437-443.
Nakagawa Y, Ratkevicius A, Mizuno M, & Quistorff B (2005). ATP economy of force maintenance in human tibialis anterior muscle. Med Sci Sports Exerc 37, 937-943.
Key Reviews
Wackerhage H & Rennie MJ (2006). How nutrition and exercise maintain the human musculoskeletal mass. J Anat 208, 451-458.
Rennie MJ, Wackerhage H, Spangenburg EE, & Booth FW (2004). Control of the size of the human muscle mass. Annu Rev Physiol 66, 799-828.