Clinical, Metabolic and Molecular Physiology
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Clinical, Metabolic and Molecular Physiology research group

Aim

The aim of our research group is to determine the mechanisms regulating mass and function of the musculosketelal system.

We endeavour to uncover the mechanisms regulating alterations in protein and energy metabolism with ageing and in disease (for example, cancer and diabetes) by combining stable isotope methodologies, molecular biology, and detailed in vivo human anatomy and physiology of muscles and tendons.

Where appropriate we also utilize more tractable in vitro (muscle cell culture) and in vivo (C. elegans) models.

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Research issue

Skeletal muscle is the body’s largest organ, accounting for approximately 40% of body mass. Maintaining heathy muscles is essential for movement and also metabolic health (e.g. blood sugar levels).

It is striking how many of the UK’s most prevalent diseases are associated with muscle wasting and/or compromised metabolic and mechanical funtion. Moreover, many of these diseases such as cancer (cachexia) and type II diabetes, are on the rise and muscle wasting in old age (sarcopenia) is a major problem given the demographic shift >70 y.

Thus, determining the basis of musculoskeletal health, its decline in disease and ageing and interventions with which to treat it, is a major health priority.  

What are we doing about...

1. Decline of muscle size and function with age?

We have characterized the metabolic, molecular, and gene expression changes that occur in ageing muscle. 

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We are now examining if the observed molecular and metabolic alterations underlie the observed structural changes and also the potential relative importance of the observed gene expression changes as a cause of muscle decline with age. We are also investigating how ageing disrupts the cross-talk between the muscle and the nervous system as a key characteristic of sarcopenia. In parallel we are testing nutritional and exercise based interventions for efficacy in restoring muscle function in the aged.

 

2. Loss of muscle mass in the clinic?

We have examined the metabolic changes that occur in muscle in a variety of clinical populations and have also identified a large number of genes and proteins that appear to influence muscle metabolism. We have established that a blunted anabolic response to feeding is a common feature in a variety of clinical populations.

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We are now attempting to understand the molecular basis for this anabolic blunting and are testing potential interventions for the ability to counter this metabolic problem. In parallel we are attempting to understand how the genes we have identified as regulating muscle metabolism do so in a coordinated function and which gene products represent promising targets for theraputic intervention.

 

Current projects

Current recent projects include:

  • Structural and metabolic determinants of sarcopenia and efficacy of concentric vs. eccentric exercise training: A novel temporospatial approach (BBSRC)
  • Application of deuterated water to define the aetiology of musculoskeletal decline in ageing and efficacy of nutritional supplements (Dunhill Medical Trust)
  • The efficacy of leucine enriched- EAA supplements vs. protein in modulation of MPS, albumin synthesis and leg/muscle blood flow in older women (Ajinomoto)
 

Outcomes

Through our research we have identified: 

  • Anabolic blunting
  • Structural changes in muscle with age, exercise and inactivity
  • A set of gene expression changes of skeletal muscle with ageing and in response to chronic loading and unloading 
  • Identified biological/structural markers of sarcopenia and disuse atrophy
  • Identified a muscle intrinsic repair mechanism
  • Identified all of the protein kinases and phosphatase required for muscle homeostasis in C. elegans

Collaborations

The group has a close interaction with the Metabolic and Molecular Physiology Research Group in the School of Life Sciences and with a number of clinical departments.

We form a central part of the MRC-ARUK Centre for Musculo-Skeletal Ageing and are members of the ARUK Centre for Sport, Exercise and Osteoarthritis.

 

 

 

Clinical, Metabolic and Molecular Physiology

Division of Medical Sciences and Graduate Entry Medicine
The University of Nottingham
Royal Derby Hospital
Uttoxeter Road, Derby, DE22 3DT


telephone: +44 (0)1332 724622
email:gem@nottingham.ac.uk