MRes Musculoskeletal Ageing course structure information

A medical practitioner assists an elderly person who is using a walking stick

Our modules cover diverse and stimulating topics that will give you an in-depth knowledge of the whole Musculoskeletal System as it ages and include:

  • The Biology of Ageing
  • Muscle in the integrated Musculoskeletal System
  • Biology, Assessment and Maintenance of Skeletal Health
  • Principles of Human Nutrition: Relevance to Ageing

There will be weekly formative tasks for you to take part in and the formal assessments include online exams, essays based on real-life scenarios and a mock grant proposal application.

    The modules are delivered by e-learning (including live interactions with tutors and peers, online lectures and presentations and discussion forums). Students study on campus and live sessions will be held between 9am and 5pm UK time. 

    Biology, assessment and maintenance of skeletal health - MED6510

    Module Co-ordinator – Enrico Dall'Ara

    Email: e.dallara@sheffield.ac.uk

    10 credits

    Aims

    The aim of the module is to make the students familiar with the structure and cellular composition of bone and with the process of bone formation and resorption. This will constitute the basis on which the students will build more specialised and cutting edge knowledge on control of bone homeostasis or loss of it with age. The students will then use this knowledge to be able to propose the correct experimental procedures to assess skeletal health in humans and experimental models and to critically evaluate interventions to prevent or delay skeletal ageing.

    Content

    The module will primarily involve private study with the material provided online. In addition students will be expected to perform their own search for information and identify key research papers to gain experience of analysing experimental work, data presentation and discussion and interpretation of results.

    Objectives

    At the end of the module the student will have:

    • Developed a systematic understanding and in depth knowledge in the following 5 areas:
    • Bone structure and mechanical properties of bone
    • Processes of endochondral and intramembranous bone formation
    • Bone remodelling and the effects of age and disease
    • Experimental models and methods of assessment of skeletal health
    • Pharmacological and lifestyle intervention to skeletal health in the ageing population
    • Have a conceptual understanding of the above 5 areas that enables them to critically
    • Evaluate current research and methodologies and develop critiques of them.

    Teaching methods

    The module will be delivered online and self-directed learning with independent study time. It also includes video lectures, screencasts, links with published papers and reports, MCQ style formative assessments, reflective journals, live lectures and live discussions of case studies.

    Assessment

    1. 2 x short essays (500 words each) – each worth 25% of the module
    2. Online SAQ (short answer question) exam – worth 50% of the module 

    Principles of human nutrition: relevance to ageing - MED6512

    Module Co-ordinator - Liz Williams

    Email: e.a.williams@sheffield.ac.uk

    10 credits

    Aims

    The aim of the module is to provide students with core knowledge of nutritional principles with a particular focus on nutrition and ageing.

    Content

    The module is composed of 5 topics, delivered over consecutive weeks:

    Topic 1 – Nutrient & energy requirements- core concepts.
    This topic is delivered in two parts

    the concept of a balanced diet, nutrient requirements, risks and recommendations the principles behind and the application of Dietary Reference Values

    Teaching methods

    The module is delivered through on-line material, screencasts, live tutorials and by directed independent study. There are short tasks, problem solving exercises and multiple choice questions associated with the topics to help assess learning and progress.

    Assessment

    The module is assessed by a short (1500 words) written report (50% of module mark) and by an online exam composed of multiple choice questions and short answers (50% of module mark).

    Topic 5 – Diet and the older adult.
    This final topic deals specifically with the nutritional requirements of older adults and current recommendations. The factors affecting dietary intake in older adults, and the methods commonly used to assess nutritional status with a particular focus on the older adult will be described.

    Objectives

    The objectives of the module are:

    To provide students with a knowledge and understanding of core nutritional principles including: dietary components, dietary reference values, inadequacy and excess, energy balance, metabolic rate, regulation of food intake, appetite and nutritional issues of particular relevance to the older adult. To provide students with an awareness of dietary and nutritional assessment skills, and the ability to critically analyse and interpret nutritional information.

    Topic 4 – Energy balance.
    This topic is delivered in two parts

    energy balance & the measurement of metabolic rate the regulation of food intake

    Topic 2 – Metabolism.
    The topic covers the characteristics of macronutrients, their metabolism and the integration of metabolism. Micronutrients that have specific importance to musculoskeletal ageing will be described.

    Topic 3 – Dietary assessment and biomarkers of intake.
    This topic is composed of two parts

    the importance and use of nutritional biomarkers the methods and limitations of dietary assessment
    Biology of ageing: principle concepts & physiological applications – MTM8016

    Delivered by Newcastle University 

    Module co-ordinator: Alison Clapp

    Email: alison.clapp@newcastle.ac.uk

    20 credits

    Aims

    - To provide a framework to understand why ageing occurs in almost all organisms and why ageing is particularly slow in humans
    - To present details of the essential mechanisms of ageing as a basis to understand how organisms age
    - To inform students on the role of intrinsic and extrinsic stress in ageing
    - To provide a critical platform to judge the efficacy of potential interventions
    - To apply the mechanisms of ageing to the physiological processes in humans and other animals
    - To present details of the development of theories in ageing research
    - To inform students of the current and likely future trends in ageing research

    Content

    - Longevity, ageing and the life cycle including the evolutionary theories of ageing
    - Mechanisms of stress and ageing: damage to protein, lipid and DNA molecules; the
    associated maintenance and repair systems; and the consequences of the accumulation of un-repaired molecular damage
    - Protein homeostasis
    - Maintenance of telomeres including telomerase; apoptosis and cellular senescence; the role of mitochondria and oxidative stress
    - Use of cell and animal model systems for ageing research
    - The mechanisms of ageing in stem cells
    - Ageing of hormonal systems
    - Ageing of extra cellular matrices
    - Molecular nutrition and its’ role in ageing
    - Female reproductive ageing
    - The role of oxidative stress in ageing
    - The future of ageing research including genetics and the use of systems biology

    Objectives

    At the end of the module students are expected to be able to:
    - Explain why ageing occurs and the role of stress in its progression
    - Summarize the key mechanisms of ageing
    - Evaluate potential interventions to slow the ageing process
    - Explain how normal ageing differs from disease
    - Use their knowledge and critical appraisal skills to judge realistically the potential of possible interventions
    - Suggest appropriate experimental procedures to address problems in biogerontology
    - Analyse why a systems approach is useful in ageing research
    - Discriminate between normal ageing and disease
    - Be aware of the current areas of research in ageing
    - Summarize age-related alterations in physiological processes

    Teaching methods

    - 24 hours “Lectures” (online material with asynchronous activity on the discussion board)
    - 24 hours tutoring time with scheduled online discussion as well as asynchronous discussion
    - 152 hours guided independent study with directed research and reading, and assessed assignment preparation

    Assessment

    1. Weekly reflective journals – worth 40% of the module - ongoing weeks 1-12
    2. Online MCQ exam – worth 30% of the module
    3. Journal article report – worth 30% of the module

    IMPORTANT: This module is delivered by the Newcastle University and as such adheres to the regulations of Newcastle University which may differ from the University of Sheffield. Where policies diverge, students will be informed at the start of the course via the student handbook.

    Muscle in the Integrated Musculoskeletal System – CIMA001

    Delivered by the University of Liverpool

    Module Co-ordinator – Anne McArdle

    Email: mdcr02@liverpool.ac.uk

    20 credits

    Overview

    This module takes a critical approach to current understanding of the biology of muscle ageing and current theories of muscle ageing, in addition to developing a broad knowledge of appropriate techniques and approaches for studying muscle ageing, within the context of an integrated musculoskeletal system. Knowledge is consolidated and practically applied in the identification of a research question and submission of a simulated grant application to the Medical Research Council, thereby providing you with the skills and knowledge to draft a grant proposal to Research Council specifications.

    Aims

    • To provide an aspect of research training in the area of muscle ageing in the integrated musculoskeletal system
    • To develop creative and critical thinking in scientific approaches to current issues in muscle ageing in the integrated musculoskeletal system
    • To allow students to have a first attempt at drafting an MRC (Medical Research Council) grant proposal and orally presenting this proposal
    • To provide students with an opportunity to experience peer review, both as a reviewer and a reviewee

    Content

    • Overview of muscle within the musculoskeletal system
    • Ageing effects on muscle and tendon
    • Generic cell/ molecular approaches to studying the musculoskeletal system
    • Model systems; advantages, disadvantages, limitations (human, cells/rodents and larger animals)
    • Muscle Ageing: Overview of Interventions
    • Detailed molecular and cell biology approaches
    • Muscle Ageing: Imaging Overview
    • Muscle: Modelling Overview
    • Writing and reviewing grant proposals to the Medical Research Council

    Objectives

    Students will be able to –

    • Identify and critically evaluate appropriate techniques and approaches for studying ageing of muscle in the context of an integrated musculoskeletal system
    • Discuss the advantages and limitations of techniques currently employed to study musculoskeletal ageing
    • Apply a systematic understanding of knowledge to produce a draft and grant application proposal to study muscle ageing
    • Explain the current understanding of the biology of muscle ageing
    • Discuss the evidence for and against current theories of muscle ageing
    • Demonstrate a critical awareness of the current gaps in our understanding of muscle ageing

    Teaching Methods

    The module will be delivered via e-learning and self-directed learning, using online lectures, presentations and tasks, student on-line discussion forums and individual and group tutorials.

    Assessment:

    • Draft grant proposal to the MRC 20% of module mark
    • Review of a draft proposal Pass/Fail
    • Final full grant proposal 60% of module mark
    • Oral presentation 20% of module mark

    IMPORTANT: This module is delivered by the University of Liverpool and as such adheres to the regulations of the University of Liverpool which may differ from the University of Sheffield. Where policies diverge, students will be informed at the start of the course via the student handbook.

    The Research Project in Sheffield

    Module code: MED6511

    Overview

    In the second semester (approx. February - August), you will undertake a 120 credit research project. You will be asked to choose from a selection of pre-existing projects (for examples of  projects that have been on offer in previous years, see download box on the right), or you are welcome to propose your own to suit your future career plans (subject to Training Committee approval).

    You will be supervised by CIMA researchers based across all 3 of the CIMA sites, giving you a truly collaborative and multi-disciplinary supervisory team. You will also partake in up to 3 weeks of placements at any of the other CIMA sites to give you the chance to liaise with your supervisors and fellow students at other institutions, to use their facilities and laboratories, or perhaps to learn a new technique.

    Placements

    As part of the research project module, you will undertake up to 3 weeks of exchange visits to either (or both) of the two CIMA sites (Liverpool and Newcastle), so that you can access facilities and resources relevant for your project. 

    Exchange visits are an integral part of the MRes because although individually each University has excellent facilities for basic science research, pre-clinical and clinical research, as a student of CIMA, you will have shared access to high-end technology and expertise, access to model systems that cover the musculoskeletal system as a whole and clinical expertise and resources not available in any single institute.

    To ensure you develop an optimal range of complementary skills and are prepared to make an informed choice about future career directions, during the research project, you will prepare a training needs analysis and a personal development plan with the help of your supervisors and tutor. This will contain approximately 200 hours worth of activities among those offered by the University of Sheffield and within CIMA. You will be required to keep a log of all your activities using the e-portfolio.

    Assessment

    Assessment for the module includes the following components:

    • 7500 word project dissertation - worth 70%
    • Oral presentation - worth 10%
    • E-portfolio and lab book - worth 20%

    It will give you practical experience in:

    • Planning research
    • Critically evaluating data from your work and others
    • Laboratory experimentation and record keeping
    • Training in writing a substantial scientific document
    • Click here for the module aims and objectives.

    Previous research projects

    Here are a few examples of research projects already completed at Sheffield as part of the MRes in Musculoskeletal Ageing. Remember, we encourage students to propose their own projects if they have any ideas of their own that would particularly fit with their future career plans and we will be happy to discuss this with students once they start the course. 

    Combining mechanical loading and anabolic therapy in postmenopausal women – a pilot study

    Background:
    The effects of mechanical loading of the skeleton are age-dependent in both animal and human models (Skerry 1997; Skerry 2008). Improvements in bone geometry and strength can be induced by loading in childhood, whereas loading in older adults seems to predominantly preserve bone mass and structure with modest, if any, improvements in site-specific geometry and mass(Hamilton, Swan et al. 2010). Several anabolic therapies, e.g. teriparatide, improve bone mass and structure (Boonen, Marin et al. 2008; Glover, Eastell et al. 2009) and have shown synergy with loading in animal models (Li, Duncan et al. 2003; Sugiyama, Saxon et al. 2008). PTH can also influence blood flow, but little is known about the effect of combined therapy on muscle. Furthermore, it is not clear if results from animal models are transferable to humans. A potential interplay between loading (whole body vibration, WBV) and low dose anabolic therapy (teriparatide) could therefore lead to enhanced but cheaper combination therapies.

    Aims and objectives:
    This project aims to establish the impact of a 48 week intervention with low dose teriparatide on bone and muscle tissues in loaded and unloaded lower legs within the same subject. Power calculations suggest that a total of 20 subjects will be sufficient.

    To reach this aim, we will:
    Investigate the impact of medium-intensity unilateral mechanical vibration on a) cortical and trabecular bone parameters assessed by Xtreme CT in the distal tibia, b) spine and hip BMD (also QCT to be considered), muscle cross-sectional area (CSA) and c) muscle strength.
    In a subgroup, we will explore the impact of teriparatide, with and without WBV, on markers of muscle protein synthesis and degradation, markers of muscle inflammation and evidence of modified Reactive Oxygen Species generation (including antioxidant defence protein and Heat Shock Protein content) and evidence of altered mitochondrial protein expression and activities. Muscle biopsies will also be examined for muscle fibre size.

    Hypothesis: There will be no difference in bone and muscle mass or function between the loaded and unloaded lower leg in older women receiving low dose anabolic therapy.

    The effect of age and body weight on vitamin D metabolism

    Background:
    Vitamin D is a major determinant of the musculoskeletal phenotype. Knowledge gaps in the handling, storage, utilization and clearance of vitamin D metabolites have hampered progress in obtaining consistency in vitamin D intervention studies for improving musculoskeletal health outcomes in ageing.

    Aims and objectives:
    We aim to assess the significance of the observation of low vitamin D in obesity and with ageing by conducting detailed measurements of bone health.
    To reach this aim, our proposal will take advantage of existing stored samples and data from current ongoing case-control studies of obese and lean children and adults of a wide age range (Study 1).

    We will:

    • Explore whether serum 25(OH)D is an appropriate biomarker of metabolic effect.
    • Investigate how vitamin D and its metabolites are handled in the body.
    • Assess how these processes vary according to body composition and life stage.
    • Elucidate the mechanisms for the observation of low 25(OH)D in obesity and ageing.

    Hypothesis:
    We will consider the following hypotheses to explain this observation:
    1. Low 25(OH)D results from low dietary vitamin D intake or low ultraviolet light (sunlight) exposure.
    2. Low 25(OH)D results from increased requirement due to changes in pool size. The consequences of low 25(OH)D would be increases in PTH, and decreases in 1,25(OH)2D and calcium absorption, with no difference in metabolic clearance rate.
    3. Low 25(OH) results from increased requirement due to increased metabolic clearance.

    An examination using murine models of the epigenetic changes that occur with age in bone marrow mesenchymal stem cells

    Background:
    In the musculoskeletal system mesenchymal stem cells (MSCs) are the common progenitors to cartilage and bone. In contrast, muscle progenitor cells reside in a different cell population, called satellite cells. Both types of stem cell are responsible for the maintenance and repair of the musculoskeletal system. Our group (IB) and others have shown that these cells undergo a process of cellular ageing (1-2), with a loss of proliferative and differentiation capacity that impacts detrimentally on tissue repair. Much like DNA polymorphism, epigenetic changes to chromatin can contribute to the ageing process. Unlike DNA polymorphism, these epigenetic changes are however plastic in nature and reversible. Epigenetic changes have been demonstrated in a number of stem cells, including MSCs aged in culture.

    Aims and objectives:
    For this studentship we will initially focus on epigenetic changes in MSCs in murine models. We will then compare the changes identified with epigenetic changes in satellite cells by collaborating with Prof. Tom Rando at Stanford University, who is running a parallel study in satellite cells.

    To reach this aim, we will:
    Validate the NestinGFP+ as bona fide MSCs.
    Determine the changes in number and properties of NestinGFP+ MSCs with age.
    Optimise the technology to determine epigenetic changes with a small number of cells.
    Determine the epigenetic changes in NestinGFP+ MSC with age.

    Hypothesis:
    Our overall hypothesis is that there are common epigenetic changes in the musculoskeletal stem cells occurring with age in vivo and that maintenance of the chromatin epigenetic state by pharmacological intervention will lead to sustained retention of stem cell properties and tissue homeostasis.

    Analysis of the upper body movements during gait for the assessment of locomotor ability

    Background:
    Age and certain neurodegenerative diseases reduce an individual’s ability to walk safely and efficiently. Consequently, gait observation and quantification is potentially a powerful tool to identify incipient pathology, contribute towards diagnostic algorithms, and quantify intervention efficiency (lord, 2013). An emerging perspective is that the movement of upper body during gait plays a critical role in successful locomotion and may provide useful information for the elderly/pathologies due to it’s relation to critical aspects of walking, such as maintenance of balance, reduction of tissue mechanical loads, and energy efficiency. Healthy individuals adopt a ‘‘head stabilization in space’’ strategy during walking. This strategy, quantified by a reduction of body segment accelerations going from pelvis to head level, is already in place in pre-pubertal age (Mazzà, 2010), and is compromised in elderly women (Mazzà, 2008). Furthermore the control of the upper body has been found to be impaired as a result of age related neurodegenerative disease such as Parkinson’s disease (Cole, 2010). As a result, Upper body variables are proposed to be able to objectively quantify gait and balance decline as a result of ageing or for diseases whereby postural control is affected. Being the lower limb movements transmitted to the upper body through the pelvis, upper body movements can also be informative of gait variability (defined as stride-to-stride fluctuations of gait parameters), which is sensitive to change due to aging, intervention, and pathology (Lord 2012), the combination of the two may be increasingly informative. However, the lack of standardized testing protocols and knowledge of reliability of gait variability measurements still limits the interpretability of this data (Galna 2013, Lord 2011).

    Aims and objectives:
    With this project, we aim at:

    • Establishing a lifespan reference metrics for the assessment of the head stabilization strategy and gait variability through devising experimental methods and data analysis techniques based on the use of wearable inertial sensors.
    • Providing reference data and measurement procedures for the clinical assessment of life-style based intervention aiming at improving locomotor function and reducing falls for the elderly. Comparisons will be made from this reference data to determine if pathological elderly groups (e.g. arthritis, Parkinson’s disease) can be identified from their respective age matched controls.
    The role of gastrointestinal hormones and identification of GI hormone receptor expressions in bone cells

    Background:

    Human body has remarkable ability to adapt to different dietary requirements. Coordinated regulatory nervous and hormonal systems control human metabolism, ensure adequate response to various dietary, physiological situations and the appropriate flux through specific metabolic pathways (Frayn, 2010).

    There are complex interactions between gastrointestinal (GI) hormones that regulate energy metabolism and bone homeostasis. These interactions are mediated directly through various calciotropic, gut and pancreatic hormones and peptides or indirectly via the endocrine organs (Talbott et al., 1998; Zeni et al., 2003, Naot and Cornish, 2008). Assessment of biochemical markers of bone formation and resorption suggest strong interlinks between food intake and bone remodeling. Abnormal dietary intake including anorexia of ageing, starvation and anorexia nervosa, and disorders of GI absorption including inflammatory bowel and celiac diseases may increase the risk of bone fractures and cause bone disorders (Bernstein and Leslie, 2003; Moss et al., 2011). These suggest that sufficient nutrient intake and normal GI function are essential for the skeletal health.

    Aims and objectives:

    The aims of this project were to analyse the expression of GI hormone receptors in two osteoblastic cell lines (SaOS-2 and Te85), stages of osteoblastic development and changes in GI hormon concentrations of fed or overnight fasted C57BL/6 mice.

    To achieve the aims we have

    • Assessed mRNA expression of GI hormone receptors in two osteoblastic cell lines using end-point PCR
    • Performed mineralisation assay to study different stages of osteoblast development
    • Measured the concentrations of insulin and glucagon hormones of fed (n=8) and overnight fasted (n=8) C57BL/6 mice using multiplex metabolic assay

    Hypothesis:

    The concentrations of metabolic hormones that have potent regulatory effects on bone formation differ during fasting and fed states. The functional activity of osteoblasts varies depending on developmental stages of osteoblast lineage. Identification of GI hormone receptor expressions in osteoblastic cell lines broadens our understanding of synergies between direct and indirect interactions of GI hormones and bone cells.


    See full course information on our Prospectus

    The content of our courses is reviewed annually to make sure it is up-to-date and relevant. Individual modules are occasionally updated or withdrawn. This is in response to discoveries through our world-leading research, funding changes, professional accreditation requirements, student or employer feedback, outcomes of reviews, and variations in staff or student numbers. In the event of any change we'll consult and inform students in good time and take reasonable steps to minimise disruption.

    Information last updated: 27 July 2020


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