A multi-disciplinary approach to understanding the mechanisms that limit exercise tolerance

Lead Research Organisation: University of Leeds
Department Name: Institute of Membrane & Systems Biology


Background: Exercise tolerance is the strongest predictor of mortality and an important determinant of quality of life across the lifecourse. However, the mechanisms that limit exercise tolerance, and how these are altered with training are poorly understood.

We have recently developed an exercise testing protocol (BB/100162X/1) that provides insight into the underpinning mechanisms that limit exercise tolerance. Furthermore, we have shown that during exercise we can systematically alter the stress on the different physiological systems that support exercise to different degrees (BB/100162X/1), and understand the systems interaction using a computational model of oxygen uptake and circulatory dynamics (BB/100162X/1).

Objectives: To determine the influence of different physiological stresses on improvements in exercise tolerance and the mechanisms that underpin this improvement in function.

Novelty: This will combine novel experimental and computational techniques to investigate for the first time how the mechanisms that limit exercise tolerance are differentially altered by divergent physiological stresses.

Timeliness: New insight into the mechanisms that limit exercise tolerance will provide therapeutic targets that can be exploited in the future to promote healthy ageing, and reduce health care costs associated with poor exercise tolerance. These costs represent a current and growing burden on health care resources.

Experimental approach: Using novel techniques developed in our labs, exercise tests will be used to measure exercise tolerance, and identify the underpinning mechanisms of the exercise limitation. Other key markers of physiological function will also be measured. These data will be used to explore the complex systems integration that limit exercise tolerance across the lifespan. Training studies will then be used to explore how the mechanisms that limit exercise tolerance respond to different physiological stresses. Again, these data will be used in combination with our computational model to understand the physiological drivers that promote specific adaptations with training.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1775136 Studentship BB/M011151/1 30/09/2016 30/03/2021 Matthew Chadwick
Description We have shown that by performing exercise with very short periods of work (approximately 10 seconds) separated by very short periods of recovery (also approximately 10 seconds), the muscle can work harder (produce more power) without increasing the perceived difficulty of the exercise or the physiological stress incurred. Additionally, we have shown that, in circumstances when the exercise is perceived as equally difficult, producing higher power does not cause an increase in the amount of fatigue (decrease in the ability of the muscle to produce power) experienced by the muscle.
Subsequently, we have demonstrated that there is no relationship between leg muscle fatigue and inspiratory muscle fatigue following short and long-duration exercise.
Exploitation Route We hope that this finding may lead to more effective exercise training strategies being prescribed to specific patient populations, particularly those with ventilatory limitations or skeletal muscle impairments such as elderly people, so that we can enhance the benefits of performing exercise for these populations. Such changes may have an impact on quality of life for the patients and reduce the financial costs associated with the healthcare provided to the patients.
Sectors Healthcare,Leisure Activities, including Sports, Recreation and Tourism

Description The Physiological Society Travel Grant
Amount £400 (GBP)
Organisation Physiological Society 
Sector Charity/Non Profit
Country Global
Start 08/2018 
End 09/2018
Description Mayo Clinic - Rochester 
Organisation Mayo Clinic
Country United States 
Sector Charity/Non Profit 
PI Contribution Collected and shared data sets to be included in the study.
Collaborator Contribution Study design, data collection, data analysis.
Impact This study will be presented at the the Annual Meeting of the American College of Sports Medicine and submitted for publication.
Start Year 2019
Description Multidisciplinary Cardiovascular Research Centre Retreat 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presented a poster outlining my research at the University of Leeds' Multidisciplinary Cardiovascular Research Centre Retreat. This provided an opportunity to discuss my research with other researchers within the University, and stimulated discussion that helped to influence the future direction of my research.
Year(s) Of Engagement Activity 2018
Description Sport and Exercise Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presented the data that I had collected at a University of Leeds Sport and Exercise Department Meeting. This led to many questions regarding the interpretation of my data and directly influenced my future data analysis.
Year(s) Of Engagement Activity 2017