Structural and metabolic determinants of sarcopenia and efficacy of concentric vs. eccentric exercise training: a novel temporospatial approach

Lead Research Organisation: University of Nottingham
Department Name: School of Medicine

Abstract

Most people will have noticed that with age people become frail. This is principally due to the wasting of skeletal muscle (a process called "sarcopenia"). Skeletal muscle wasting occurs not only with older age but also with a large number of common illnesses: trauma, burn injury, diabetes, cancer, heart failure, renal failure, Alzheimer's disease, and arthritis (to name but a few). Crucially, in these cases, muscle wasting is more than just a symptom of weakness and poor functional capacity. Muscle wasting exposes us to an increased risk of falls and fractures, which often lead to death within a year in the aged. Thus, muscle wasting occurring in disease and with age impacts on quality of life, independence, morbidity and mortality and represents a major UK health problem. However, we currently understand little about the processes that regulate sarcopenia in humans. The best-known means by which to counter muscle wasting occurring in older age is exercise. For example, if one were to look at a body builder they would notice the gross musculature gained (called "hypertrophy") from lifting weights. While muscle growth on this scale is not possible in older age, a degree of muscle growth and functional improvement can be achieved. Finding optimal exercise strategies with which to counteract sarcopenia is therefore an important goal.

In the current proposal we have developed a novel strategy to explore human sarcopenia and exercise strategies with which to offset it. We have recently found that sarcopenia manifests in two "spatially" different ways. Sarcopenic muscles display wasting due to reductions both in muscle "length " at the muscle end, and muscle "width" along the mid-section. Therefore, our first goal is to study older and younger people over a period of 2 months to define the process(es) responsible for loss of muscle length AND width in sarcopenia. To achieve this we will provide young and older volunteers with daily drinks of "labelled water" from which we will be able to track longitudinal changes in important aspects in the building processes of muscle (by taking intermittent muscle samples from the muscle middle and end) over this entire period. This approach will explain why human sarcopenia is spatially distinct.

Secondly, we propose to assess excercise interventions for reversing human sarcopenia. Conventional resistance exercise is composed of both lengthening and shortening muscle contractions (touch your shoulder and imagine lowering down a dumbbell (lengthening) and then lifting it again (shortening). Intriguingly, when exposing individuals to either exclusive lengthening or shortening exercise training we have found that lengthening exercise increases muscle length and shortening exercise increases muscle width. Herein we propose to trial the efficacy of lengthening and shortening contractions in counteracting spatial differences we have identified in sarcopenia while also studying the mechanisms underlying why these contractions work the way they do. To achieve this we will provide young and older volunteers with daily drinks of "labelled water" during either lengthening or shortening contraction training after which we will be able to track longitudinal changes in important aspects in the building processes of muscle (by taking intermittent muscle samples from the muscle middle and end) over this entire period in youth and ageing.

This project will have significant, perhaps groundbreaking, implications for our understanding of the control of skeletal muscle size in humans, particularly in relation to the problem of sarcopenia.

Technical Summary

We propose to take a human systems physiology approach that couples whole body functional, whole tissue anatomic, and sub-cellular molecular and metabolic measures to address the molecular basis of sarcopenia, the molecular basis of exercise induced muscle growth, and optimal strategies with which to use exercise to counteract sarcopenia. We have shown that sarcopenia (viewed by DXA/ MRI) is due to specific architectural changes on an individual muscle level, viz: loss of sarcomeres in series and sarcomeres in parallel (by ultrasound). To determine the basis of these changes, we will sample tissue at the muscle mid-belly (loss of sarcomeres in parallel) and close to the distal aponeurosis (loss of sarcomeres in series). Using a new tracer (D2O) approach we will measuring turnover of muscle sub-fractions (e.g. myofibrils, myoplasm, mitochondria, nuclei [satellite cells]) and correlate these with standard measures of anabolic signalling (e.g. detection of phosphorylation events in these pathways). Data from these measures will then be correlated with tissue level changes and defined by comparison to a younger group to seek age x spatial architecture/ spatial metabolic differences such to identify the dynamic metabolic underlying sarcopenia. Next, we will determine the longitudinal and spatially distinct alterations in architecture, signalling, and metabolism (as above) in response to concentric (CON) vs. eccentric (ECC) contraction by comparison to a young population to seek contraction x age x spatial architecture/ spatial metabolic differences. This will inform on (i) dynamic processes regulating distinct spatial adaptations to ECC/CON and (ii) the efficacy of ECC vs. CON in reversing spatially distinct aspects of sarcopenia. Lastly, we will measure the effect of ECC vs. CON in functional terms (e.g. strength gains, improved gait, improved balance, etc.) to determine if ECC or CON is more effective at combating the functional consequences of sarcopenia.

Planned Impact

In addition to academic beneficiaries we believe this work will benefit, the wider public, the commercial private sector, charities, and the staff working on the project. Academic beneficiaries will be the wider muscle community as we will provide innovative knowledge on the mechanisms of muscle growth in response to different modalities of mechanical loading, the causes of the blunted anabolic response to resistive training in old age, and proof of concept of the efficacy of repeated, submaximal muscular exercise for combating sarcopenia and weakness in old age. Additionally, we will develop a new resource for use by other scientists in the field. Our muscle protein synthesis (MPS) determination by D2O method provides an unprecedented method for studying the temporal and sub-cellular variations in muscle protein metabolism based on chronic rate determinations of MP; many groups will likely use this approach for mechanistic research into hypertrophy and sarcopenia. The wider public will benefit from this work in the form of improved diagnosis and treatment of sarcopenia, ultimately (it is hoped) decreasing public healthcare expenditure. We will directly examine the type, modality and impact of muscle loading exercise regime most efficacious for treating sarcopenia. Within 3-5 years this could reduce the public healthcare expenditure for conditions associated with declining muscle health (for example in this case the aged) though reducing economic burden of sarcopenia and perhaps to wider prevalent conditions associated with muscle atrophy i.e. cancer, type II Diabetes. Even more broadly all sectors of the UK could benefit from increased productivity as the result of decreased loss of work days due to muscle problems. Importantly, as we are members of a new MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research we are uniquely positioned to conduct BBSRC funded basic research and interact with those engaged in seeking treatments for the decline of muscle with age. If exercise proves effective, we can therefore start the translational process as soon as the end of the second year of this project and demonstrate true cross council prioritization of muscle aging research. The commercial private sector will benefit in the development and commercialisation of innovative training contraptions targeted at restoring muscle mass of older individuals. These impacts will be felt within the third year as we present and publish our results of these exercise interventions. Charities will also benefit in much the same way, particularly those charities that support increased quality of life in individuals with problems that involve musculoskeletal frailty, loss of mobility and increased risk of falls (for example: Research into Aging) and Arthritis Research UK who is committed to reducing decline of the entire musculoskeletal system with age. Lastly, the staff working on this project will benefit in two ways. The post-doctoral researcher will gain training in in vivo protein metabolism assessment using this innovative D2O methodology, molecular biology, muscle ultrasound and muscle function, and in the physiological awareness of sarcopenia. The appointed technician will gain unique experience running this new method of assessment of human protein synthesis, thereby strengthen his/her skill-set. Both of these types of professional development will aid in their ability to seek further employment, with additional training in project management being the most transferable skill they will continue to develop. These impacts will be felt within the first year and fully realized in 2-4 years.

Publications

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Mitchell WK (2017) Eccentric Exercise and the Critically Ill Patient. in Frontiers in physiology

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Narici M (2016) Muscle structural assembly and functional consequences. in The Journal of experimental biology

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Quinlan JI (2018) Muscle and Tendon Contributions to Reduced Rate of Torque Development in Healthy Older Males. in The journals of gerontology. Series A, Biological sciences and medical sciences

 
Description The project 'Structural and metabolic determinants of sarcopenia and efficacy of concentric vs. eccentric exercise training: a novel temporo-spatial approach' has entered its 3rd and final year. Now we report the following results:
1) Comparison of muscle morphological (muscle architecture, muscle mass) and functional characteristics (muscle strength, activation capacity, rate of torque development) of the young (YM) and older (OM) male cohorts
2) Comparison of the tendon mechanical properties (tendon stiffness and Young's Modulus) of the YM and OM cohorts and their role, together with neural drive and muscle size, to the speed of force development in the YM and OM cohorts.
3) Comparison of the time-course of the morphological adaptations of the YM and OM participants to 8-week resistive exercise training programme based on either shortening contractions (concentric, CON) or lengthening contractions (eccentric, ECC).
4) Temporal response and mechanisms of muscle protein and collagen synthesis to different modes of exercise in YM vs OM

Results
1) Muscle architecture, muscle volume and muscle function of YM and OM
OM demonstrated a 32% lower isometric MVC ('static maximum contraction force') and a 25% smaller quadriceps muscle CSA compared to YM. Quadriceps voluntary activation (AC) during maximal leg extension was 4% lower in OM than in YM, and muscle twitch CT was 21% longer in OM . Also, the rate of motor unit recruitment (rate of EMG development) was significantly 42% slower in OM than in YM. Absolute RTD was 34.5% lower in OM. The age-related reduction in RTD was maintained after normalization of RTD to peak CSA (nRTD).

2) Tendon mechanical properties and related functional outcomes
Patellar tendon dimensions (CSA and length) of YM and OM respectively were found to be unaffected by age. Patellar tendon stiffness was found to be 31% lower in OM. Young's modulus demonstrated the same trend as stiffness. No differences in either fascicle length or in resting fascicle: tendon ratio were detected.
RTD correlated with AC, rate of EMG development, CSA, MVC and tendon stiffness. However, nRTD was found to be significantly correlated with tendon stiffness and MVC.

These observations provide evidence that in absolute terms, a lower RTD in the elderly is caused by a slower muscle contraction speed, slower TTPE, a reduction in muscle CSA and a decrease in tendon stiffness. Significantly, however, the only variable to remain correlated once the RTD is normalized to quad CSA, is tendon stiffness. This strongly reinforces the importance of both muscle and tendon characteristics when considering RTD, but especially the stiffness of the tendon. This has implications for the design of interventions aiming at improving postural stability and preventing falls in older people.

3) Time-course of the morphological adaptations to resistive training (RT) of YM and OM
Twenty-four healthy volunteers (12 YM, 19-30 yrs, and 12 OM, 65-73 yrs) were recruited for this investigation. YM and OM were randomly assigned to either an ECC (n=6) or CON (n=6) RT group: volunteers were trained 3 times/wk for 8 weeks (12-15 reps x 4 sets) at the 60% of either the ECC or CON 1RM. Changes in vastus lateralis (VL) architecture (fascicle length -Lf, and pennation angle - PA) were assessed by ultrasound technique. Quadriceps mid-thigh (50% of VL length) cross sectional area (CSA) was measured by extended field of view (EFOV) ultrasound technique. The data acquisition was performed at 0, 2, 4, 6 and 8 weeks of the training regime.
Contraction-specific responses in muscle architecture were found with RT:
i) a preferential increase in Lf was found after ECC, while PA showed greater increase after CON RT.
ii) YM ECC group showed a faster and greater increase in Lf compared to the ECC OM group since 2 weeks from the start of the protocol (+2.84%) which was maintained at 4,6 and 8wks.
iii) CSA showed similar increase and time course pattern with both loading types (ECC or CON) across ages (YM vs. OM): however, in OM, ECC presented a greater CSA increase at 4 and 6 wks compared to CON.

These findings show that structural changes are achieved earlier and in a greater manner by moderate-load ECC in YM compared to OM. In OM, the more rapid increase in muscle CSA in response to ECC indicates that moderate-load ECC exercise could be a more time-efficient hypertrophic stimulus than moderate CON RT.

4) Temporal response and mechanisms of muscle protein and collagen synthesis to different modes of exercise in YM vs OM
Progress with regard to the synthesis measures of muscle and tendon has been hampered by significant technical issues with the Isotope Ratio Mass Spectrometer that makes the very sensitive measures of deuterated Alanine incorporation into muscle protein and tendon collagen. So, at this point we have been unable to compare the effect of the different modes of exercise on protein turnover in these tissues. The muscle samples have been extracted and prepped ready for analysis and some method development work on some of the Tendon samples has demonstrated quite clearly via the incorporation of deuterated Alanine in collagen extracted from Tendon, that we can measure the rate of incorporation of label into Tendon, albeit the rate of turnover is markedly less than muscle myofibrillar protein - in line with data from the literature from acute measures.
With regard to the technical issues this required significant input from the instrument vendor over a protracted period of time (approx. 12 months), but we now believe we have identified a build-up of material in capillaries leading from the reactor (the reactor is set at 1400oC and is responsible for generating the H2 gas from the Alanine) which ultimately back up into the reactor causing a dilution of the deuterium labelling in subsequent samples leading to significant dilution of the label and underestimation of the incorporation rate (synthesis). Such is our confidence that we have overcome this issue that we have acquired a second instrument to make these measurements ensuring we can double throughput and capacity (we have many studies involving D2O that are ongoing and in planning - we have 2 grants from the Dunhill Medical Trust and Industry funding that will use this approach) importantly the acquisition of this new mass spectrometer will reduce the back-log of samples that have built up over the last 12 months. We anticipate completing the Muscle synthesis and Tendon collagen synthesis measures from this study over the next 6 months.
Exploitation Route BASED ON OUR PRELIMINARY RESULTS:

1) Formulation of new exercise protocols aimed at improving muscle mass in young and older populations in health and disease.

2) Novel information on the morphological adaptations of human skeletal muscle to eccentric (lengthening) and concentric (shortening) loading excercise and how these are affected by age
3) Novel information on regional differences in human skeletal muscle morphological and molecular responses to eccentric and concentric resistive exercise.
4) New insights into the mechanisms of muscle ageing and muscle hypertrophy in response to different loading modes.
5) Elderly tendons are less stiff (i.e. more easy to stretch) than young tendons and this seems to account for the slower rate of force development during rapid contractions. This observation may have important implications for the avoidance of fall in the elderly as rapid force development. This is essential for fast transmission of force generated by the muscle to bones, enabling a quick counteraction, as needed when tripping over an object.
Sectors Aerospace, Defence and Marine,Agriculture, Food and Drink,Communities and Social Services/Policy,Education,Electronics,Healthcare,Leisure Activities, including Sports, Recreation and Tourism,Manufacturing, including Industrial Biotechology

 
Description BBC Trust me I'm a doctor - we used methods in this grant to attract significant media attention
First Year Of Impact 2016
Sector Education,Healthcare,Other
Impact Types Societal

 
Description Our group will host the ESPEN international tracer course on metabolism - this will impact researchers stable isotope technology applications
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
URL http://icu-metabolism.se/onewebmedia/CTMM2016_Flyer%202.pdf
 
Description Abbeyfield Studentship
Amount £100,000 (GBP)
Organisation Abbeyfield 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2016 
End 01/2019
 
Description Biomedical Research Centre Musculoskeletal Disease Theme
Amount £23,600,000 (GBP)
Organisation Department of Health (DH) 
Sector Public
Country United Kingdom
Start 01/2018 
End 12/2022
 
Description Industry Funding
Amount £35,000 (GBP)
Organisation GlaxoSmithKline (GSK) 
Sector Private
Country Global
Start 04/2017 
End 10/2018
 
Description MRC Doctoral Training Grant
Amount £60,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2014 
End 03/2017
 
Description NCESM
Amount £100,000 (GBP)
Organisation Loughborough University 
Sector Academic/University
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description Programme Grant
Amount £73,000 (GBP)
Organisation The Dunhill Medical Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2018
 
Description Programme Grant
Amount £100,000 (GBP)
Organisation The Dunhill Medical Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2016 
End 03/2019
 
Description iCASE PhD Studentship
Amount £140,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 08/2020
 
Title Deuterium Oxide stable isotope to quantify multiple aspects of metabolism in vivo 
Description We have developed, validated and applied methods to quantify fat, protein and DNA metabolism concurrently in humans. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2015 
Provided To Others? Yes  
Impact Ensuing publications revealing that long term measures of muscle protein synthesis are listed in older age - explaining for the first time why older muscle is less malleable to anabolic interventions. 
 
Title Isolated concentric/eccentric muscle loading device 
Description This research tool enables to load human muscles either only concentrically (i.e. using shortening contractions) or eccentrically (using lengthening contractions). The device consists of an electrical winch attached to a weight training machine enabling the subject to perform concentric only' exercise or 'eccentric only' exercise. 
Type Of Material Improvements to research infrastructure 
Year Produced 2014 
Provided To Others? Yes  
Impact Several research groups of the University of Nottingham are using this adapted exercise device and its use supports various undergraduate and postgraduate research projects. 
 
Title Ultrasound assessement of muscle architecture and muscle cross-sectional area 
Description State-of-the-art B-mode ultrasonography has been applied for the investigation of human skeletal muscle architecture in vivo to phenotypically characterise sarcopenic muscle and assess the changes thereof induced by resistive exercise interventions. A new ultrasound-based research tool has been developed for the assessment of muscle cross-sectional area through the use of extended-field of view (EFOV) ultrasound. This method enables to perform a tomographic scan of the muscle in the axial (transverse) plane and obtain a cross-sectional image of the muscle investigated. The technique was tested against MRI and found to be highly correlated. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2016 
Provided To Others? Yes  
Impact Several research groups in our medical school are now using the above two techniques in current research studies, including undergraduate and postgraduate research student projects. Also, Professor Narici has been invited to contribute to a clinical perspective review paper on the use of muscle ultrasound for the study of sarcopenia in older individuals (Ticinesi A, Meschi T, Narici MV, Lauretani F, Maggio M. Muscle Ultrasound and Sarcopenia in Older Individuals: A Clinical Perspective. J Am Med Dir Assoc. 2017 Feb 12. pii: S1525-8610(16)30545-X.) 
 
Title Extended Field of View Ultrasound (EFOV) 
Description EFOV generated data affords new insights into the regional changes of human skeletal muscle associated with sarcopenia and the adaptations to resistive exercise. Furthermore, EFOV ultrasound affords the acquisition of muscle cross-sectional images with an accuracy comparable to MRI. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact The EFOV technique has now become routine in most projects on human skeletal muscle performed at the Derby Campus of the MRC-AR UK Centre for Musculoskeletal Ageing of Nottingham University. 
 
Title HUMAN_ECC_CON 
Description Biological samples (blood, tissue) that could be exploited in the future for phenotyping purposes. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Future contribution of biological samples to chart studies to interrogate the mechanisms of ageing; including applying metabolomic profiling to attempt to uncover novel biomarkers/mechanisms underlying muscle growth and hypertrophy. 
 
Description Liverpool John Moores University 
Organisation Liverpool John Moores University
Department Faculty of Engineering and Technology
Country United Kingdom 
Sector Academic/University 
PI Contribution A collaboration with Professor Constantinos Maganaris was initiated by the PI of this project to add investigations into the tendon adaptations to strength training in the young and older individuals recruited for our project. Professor Maganaris has been involved in this project as external advisor for the investigations into tendon mechanical properties assessed in vivo using ultrasonography. These investigations are currently supporting a PhD project of a MRC-funded student.
Collaborator Contribution Professor Maganaris has been instrumental for the setting up of the measurements of tendon mechanical properties in vivo and for advising on the data analysis and result interpretation. This collaboration has resulted in a manuscript comparing tendon mechanical properties of young and older individuals and the impact of tendon stiffness in the rate of force development in young and older individuals. The manuscript is due to be shortly submitted for publication in the Journal of Gerontology. Plans to extend these analyses to the intervention study are in place with the aim to compare the muscle and tendon adaptations, and their time-course, to resistive training in the young and older participants of this project.
Impact Abstract presented at the 2017 Advances in Skeletal Muscle Biology in Health and Disease, University of Florida meeting, 8-10 March, 2017, Gainesville, FL, USA.
Start Year 2016
 
Description University of Zurich 
Organisation Balgrist University Hospital
Country Switzerland 
Sector Academic/University 
PI Contribution The Research Fellow Dr Martino Franchi working on this grant initiated a collaboration with Professor Martin Flueck of the Balgrist Hospital, ETH, given his leading expertise in mechanotransduction.
Collaborator Contribution Professor Fluck offered to collaborate to our project by performing analyses on tissue portions of the muscle biopsies collected in our project with the intent of measuring the activity and content of focal adhesion kinase (FAK). This analyses will provide insights into the molecular mechanisms responsible for the remodeling of human skeletal muscle in response to resistive training in young and older individuals,
Impact This collaboration has so far focused on samples collected in young individuals in a previous study with similar training protocol to the present one. The results obtained have been recently presented by Dr Franchi at the Muscle Biology meeting of the University of Florida (2017 Advances in Skeletal Muscle Biology in Health and Disease)
Start Year 2016
 
Description University of Zurich 
Organisation Liverpool John Moores University
Department Research Institute for Sport and Exercise Sciences (RISES)
Country United Kingdom 
Sector Academic/University 
PI Contribution The Research Fellow Dr Martino Franchi working on this grant initiated a collaboration with Professor Martin Flueck of the Balgrist Hospital, ETH, given his leading expertise in mechanotransduction.
Collaborator Contribution Professor Fluck offered to collaborate to our project by performing analyses on tissue portions of the muscle biopsies collected in our project with the intent of measuring the activity and content of focal adhesion kinase (FAK). This analyses will provide insights into the molecular mechanisms responsible for the remodeling of human skeletal muscle in response to resistive training in young and older individuals,
Impact This collaboration has so far focused on samples collected in young individuals in a previous study with similar training protocol to the present one. The results obtained have been recently presented by Dr Franchi at the Muscle Biology meeting of the University of Florida (2017 Advances in Skeletal Muscle Biology in Health and Disease)
Start Year 2016
 
Description University of Zurich 
Organisation University of Florida
Department Department of Physiology and Functional Genomics
Country United States 
Sector Academic/University 
PI Contribution The Research Fellow Dr Martino Franchi working on this grant initiated a collaboration with Professor Martin Flueck of the Balgrist Hospital, ETH, given his leading expertise in mechanotransduction.
Collaborator Contribution Professor Fluck offered to collaborate to our project by performing analyses on tissue portions of the muscle biopsies collected in our project with the intent of measuring the activity and content of focal adhesion kinase (FAK). This analyses will provide insights into the molecular mechanisms responsible for the remodeling of human skeletal muscle in response to resistive training in young and older individuals,
Impact This collaboration has so far focused on samples collected in young individuals in a previous study with similar training protocol to the present one. The results obtained have been recently presented by Dr Franchi at the Muscle Biology meeting of the University of Florida (2017 Advances in Skeletal Muscle Biology in Health and Disease)
Start Year 2016
 
Title Muscle Ultrasound 
Description The use of muscle ultrasound to quantify mass and as a clinical diagnostic for low muscle mass (comparing MRI). This grant has both MRI and US which we are comparing performance/ diagnostic capacity. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2016
Development Status Actively seeking support
Impact N/A as of yet. 
 
Title Tendon Biopsy Technique 
Description Two members of our team visited collaborators in Copenhagen for training in the procedure for acquiring tendon biopsies. This surgical technique is now available for regular use within this project and future muscle-tendinous research undertaken by the team. This will provide mechanistic insight into the regulation and turnover of tendon tissue in response to different modes of exercise in young and elderly volunteers 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact The technique has been utilised throughout this project, without mishap and represents an important tool in understanding tendon biology. 
 
Title Muscle ultrasound 
Description Ultrasound and extended field of view ultrasound validated to match MRI to quantify muscle mass and detect low muscle mass 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2015 
Impact development of convenient non-invasive methods to quantify muscle mass accurately 
 
Title deuterium oxide stable isotope tracer 
Description Use of GC-IRMS-Pyrolysis and deuterium oxide tracers to quantitate in vivo metabolism 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2014 
Impact The ability to simultaneously quantify in vivo macronutrient substrate metabolism 
 
Description BBC Trust me Im a Doctor 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Team appeared on BBC Trust Me I'm a Doctor. Substantial section on skeletal muscle mass and exercise with ageing i.e. running a home based intervention to improve muscle function older people.
Year(s) Of Engagement Activity 2015
 
Description Primary School Visit- Walter Evans 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact We visited a primary school where we gave a talk about how and why to do a biology experiment in space and had hands on activities including handling spaceflight harware, examining normal and mutant worms, assessing hand grip strength, and assessing blood pressure. The audience was comprised of approximately 100 year 5 and year 6 students, their teachers, and other staff from the school. Feedback from the students and staff was that they enjoyed the event and were very interested in learning more about our next space mission.
Year(s) Of Engagement Activity 2019
 
Description Research Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Members of the public (including children), students, patient groups and volunteers were invited to the medical school to see the range of research activities that were ongoing. Including demonstrations of human physiology, exercise bikes, ultrasound to demonstrate effects on blood flow muscle architecture and other techniques. Results from a number of recently completed human studies were also presented and volunteers (and general public) were able to discuss the outcomes in the context of healthy living.
Year(s) Of Engagement Activity 2015
 
Description School Visits 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Main purpose is to get children interested in and talking about science and health. Members of our research team are involved in designing the workshops, taking the workshops into schools within Nottinghamshire and Derbyshire. Undergraduate and postgraduate students then run these workshops, we have 3 workshops that are rolled out to 3 schools, so at least 9 visits involving approximately 90 students, and follow up tasks are given to the teachers to assess the impact in terms of their recall and interest. One workshops is based around muscles (might muscles) and the children learn about exercise and the role of their muscles, one is around healthy eating (Eating for Energy) in which they learn about different macronutrients, portion size in relation to being active and the third is around hygiene (Litterbugs) in which the children are encouraged to have good hygiene, wash their hands and are told about bacteria.
Year(s) Of Engagement Activity 2013,2014,2015,2016