Determining the effectiveness of novel nutraceutical compounds to support skeletal muscle proteostasis during ageing and disuse.

Lead Research Organisation: University of Birmingham
Department Name: Sport, Exercise & Rehabilitation Science

Abstract

Throughout the lifespan, skeletal muscle mass is regulated through dynamic changes in protein metabolism in response to physical activity and nutritional status. Short-term periods of unavoidable musculoskeletal disuse (i.e. during injury/illness) are often accompanied by significant declines in muscle mass due to a dysregulation between myofibrillar protein synthesis (MPS) and degradation (MPB) rates. In otherwise healthy individuals, these acute decrements to skeletal muscle mass are primarily attributed to a blunted response of MPS to exercise and nutrition (termed 'anabolic resistance'), with basal MPS remaining depressed throughout the disuse episode. Therefore, in theory, by manipulating potent anabolic stimuli (i.e. physical activity or nutritional status), it is possible to attenuate the negative response of skeletal muscle protein metabolism to periods of short-term disuse. This PhD project will use a cell-to-human model that aims to determine the effectiveness of three novel nutraceutical compounds (leucine, phosphatidic acid and epicatechin) to attenuate skeletal muscle disuse atrophy and analyse the biological mechanisms that underpin the response of skeletal muscle protein metabolism to the ingestion of these compounds. Consequently, this work could provide novel and feasible interventions to attenuate skeletal muscle atrophy during acute periods of unavoidable physical inactivity throughout the lifespan, thus prolonging an individual's health span.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1898477 Studentship BB/M01116X/1 02/10/2017 30/09/2021 Sophie Jacqueline Edwards
 
Description The amino acid leucine was unable to prevent the loss of leg strength and muscle mass that is assosiated with 7 days of muscle disuse, by means of a leg cast. Interestingly, we also found that following muscle disuse, mitochondrial protein synthesis was decreased in the immobilised limb compared to the control limb. This is a novel finding and as a result, we are now investigating the role of nutritional interventions that target mitochondrial pathways as a means to offset muscle loss during disuse.
Exploitation Route It may help determine the role of mitochondria to offset muscle disuse atrophy.
Sectors Healthcare

 
Description Are markers of skeletal muscle mitochondrial content and autophagy-mediated proteolysis altered in chronic kidney disease patients? 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution To conduct western blot analysis and data quantification.
Collaborator Contribution Provided samples from CKD patients and expertise for the completion of a mini-project during the training year of the MIBTP program.
Impact Poster-presentation at the MIBTP symposium 2018.
Start Year 2018
 
Description Coco flavanols and muscle disuse atrophy 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution To undertake the in vitro to in vivo research, from study design to completion.
Collaborator Contribution To aid with study design and data collection. The collaboration will also provide the supplementation.
Impact This collaboration is ongoing.
Start Year 2019
 
Title ClinicalTrials.gov Identifier: NCT03762278 
Description Please see ClinicalTrials.gov Identifier: NCT03762278 for further information. 
Type Preventative Intervention - Nutrition and Chemoprevention
Year Development Stage Completed 2020
Development Status Closed
Impact n/a 
 
Description European Congress of Sport and Exercise Sciences Annual Conference 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Roughly 100 people attended my presentation at ECSS, which sparked questions afterwards. The feedback from the presentation was very positive.
Year(s) Of Engagement Activity 2019