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Dynapaenia and sarcopaenia: modelling the drivers of age-related functional decline to generate protective strategies


Project Description

The University of Exeter EPSRC DTP (Engineering and Physical Sciences Research Council Doctoral Training Partnership) is offering up to 4 fully funded doctoral studentships for 2019/20 entry. Students will be given sector-leading training and development with outstanding facilities and resources. Studentships will be awarded to outstanding applicants, the distribution will be overseen by the University’s EPSRC Strategy Group in partnership with the Doctoral College.

Supervisors:

Associate Professor Joanna Bowtell, Department of Sport and Health Science, College of Life and Environmental Sciences
Professor Krasimira Tsaneva-Atanasova, Department of Mathematics, College of Engineering, Mathematics and Physical Sciences

Project description:

This project will introduce an interdisciplinary approach, combining mathematical modelling with a suite of biomechanical and neurophysiological measures, to better understand the process of muscle loss and strength that occurs with ageing, and how to prevent it; thus extending capacity for independent living.

Background: Progressive age-related loss of muscle mass (sarcopenia) and associated loss of strength can severely affect quality of living for elderly individuals. Losses commence in the 4/5th decade and accelerate from the 6th decade onwards with per annum losses in the order of 0.5 – 1.5 %. This is associated with reductions in strength and consequently reduced capacity of elderly individuals to carry out the necessary activities of daily living leading to a loss of independence and impaired quality of life (2). The global 60y plus population will triple from 600 million in the year 2000 to more than 2 billion by 2050, and statistics suggest that 5-13 % of those aged 60-70 y and 11-50% of those >80y suffer from sarcopenia (3). There is therefore an urgent need to improve our understanding of sarcopenia and loss of muscle strength, and to generate innovative evidence-based solutions. Sarcopenia occurs as a consequence of both fibre atrophy and reductions in motor unit numbers, due to loss of alpha-motor neurons. However, the causes and relative contributions of these processes are not yet understood. In addition many other neuromuscular factors besides sarcopenia contribute to age-related loss of muscle strength such as reduced central drive, contractility and excitability.

The PhD project: The purpose of this PhD studentship is firstly to quantify the relative contribution of different neurophysiological and neuromechanical factors to age related decline in muscle function. A three-pronged interdisciplinary approach will be employed:
1. Empirical data collection on populations of different age and training status will characterize a broad range of neurophysiological and neuromechanical factors that are expected to contribute to loss of muscle function.
2. Mathematical models will be developed that can interrogate the above cross-sectional data sets and distinguish key factors contributing to sarcopenia with ageing that can be targeted with interventions
3. Intervention studies using strength loss induced by limb immobilisation, will target the factors identified by models. This stage will test the efficacy of novel strategies to counteract strength loss.

The PhD project will provide an exciting opportunity for the student to train in the use of advanced neurophysiological and biomechanical methods for assessing muscle function. Investigations of young and old (masters) athletes and age-matched controls will include use of dynamometry, magnetic resonance imaging (muscle volume), and ultrasound imaging (muscle thickness, pennation angle, fascicle length) to attain muscle strength and architectural parameters. Assessment of neuromuscular function will include using both surface and intramuscular electromyography for estimation of motor unit numbers, as well as evoked contractions via peripheral nerve stimulation and transcranial magnetic stimulation to assess contractility, excitability and central drive. We will use this data to inform a mechanistic model of the coupled neuromuscular system based on differential equations. The model will be used to probe the effects of aging on muscle function by varying relevant model parameters and possibly performing bifurcation analysis. This would allow the student to investigate and identify the main factors contributing to age related decline in muscle function. Subsequently, limb immobilisation will be used to mimic the age-related loss of muscle function and mass, in order to test the model and also to allow evaluation of the protective effects of innovative strategies.

Suitable candidates will have completed a BSc in a related area and will ideally either have experience of making measurements of neuromuscular function or expertise in mathematical modelling. However, training will be provided to the successful candidate in all of the techniques involved.

Funding Notes

For successful eligible applicants the studentship comprises:

- An index-linked stipend for up to 3.5 years full time (currently £14,777 per annum for 2018/19), pro-rata for part-time students.
- Payment of University tuition fees (UK/EU)
- Research Training Support Grant (RTSG) of £5,000 over 3.5 years, or pro-rata for part-time students

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