Centre for Integrated research into Musculoskeletal Ageing (CIMA) Renewal

Overview
The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA) is a unique team. CIMA brings in a mix of skills from three major U.K. Universities: Liverpool, Newcastle and Sheffield. It helps doctors and lab scientists to work together to grasp:
1) How our muscles, bones and joints change as we age.
2) How this makes some people prone to problems with these tissues such as arthritis and osteoporosis.
3) What each person can do to reduce the risk of developing these problems.

Progress So Far
CIMA was first funded for 5 years in 2012. CIMA has made great progress in figuring out some key processes in muscles, bones and joints as we age. As well as working out what might reduce the risk of developing these problems, we have also done trials of some likely nutritional agents. These might reduce age-related decline in muscles, bones and joints. We have obtained some early evidence that raising vitamin D may help reduce age-related decline, but putting up nitrate intake may not help. A big limit to expanding research in this important area has also been a lack of well-trained researchers and doctors. So the Centre has also developed and run good training courses to meet this need.

Future: Targets, Treatments & Training
This bid is for 5 more years of funding from the Medical Research Council (MRC) and Arthritis Research UK to help build on this work. Our first phase of funding has let the CIMA members spot certain changes to cells- called epigenetic changes. These seem vital in influencing whether muscles, bones and joint tissues decline quickly or slowly as we age. We plan to do a linked research programme across Liverpool, Newcastle and Sheffield. This will seek to work out the importance of these changes and whether we can modify the changes to reduce the risk of getting muscle, bone and joint problems. We will also work together to look more closely at whether nutrition and exercise can prevent or reduce the risk of these problems. We also plan to expand our training programme so more basic scientists and doctors can do excellent research into these problems. Key results will be shared in papers and meetings. More funding bids will be made to do this work.

Patient View
People with arthritis have helped to shape this bid. By joining a series of "Arthritis Matters" Public Engagement events, for example. These have helped the public grasp CIMA's research and shape future priorities. Above all this includes a grasp of new arthritis treatments and how study findings can benefit patients. We also asked a group of 15 patients to advise on the final lay summary. We think talking to patients often about research and listening to their views makes for better research.

Better Engagement
Going forward, patients and the public will continue to be actively involved by providing insight and valued feedback in many ways. Face to face meetings will remain a key part. And more events will be used, including local, national and global schemes. There will be new work with schools, to share CIMA's work, inspire new ideas and nurture talent. The VOICE North digital platform will support this across the Centre and more widely. The CIMA website will also be kept up to date and advances shared on Twitter. We know most older people don't use these yet, but that could change quickly as access gets easier and cheaper. We expect young people to help make solutions for this. We will also increase our work with drug companies, local authorities and the NHS. This will allow us to develop ways to make sure our findings are quickly put into practice to benefit older people. Arthritis is also one of a key number of conditions included in the NIHR James Lind Alliance Priority Setting Partnership on Ageing and Multiple conditions, led by Newcastle University. This will provide more chances for patients who have arthritis to be involved and link to CIMA.

The MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) brings together scientific and clinical expertise in different disciplines from the universities of Liverpool, Newcastle and Sheffield. Formed in 2012, CIMA has developed an integrated approach to study the effects of ageing on the musculoskeletal system, which has been demonstrably successful. CIMA has focussed activities in areas of critical mass where collaborations have provided enhanced value. These include the role of epigenetic changes in cells and tissues affected by musculoskeletal ageing, development of an assessment protocol for monitoring age-related decline in the musculoskeletal system (the CIMA Toolkit), and proof of principle pre-clinical and human studies to identify interventions that reduce the deleterious effects of ageing on the musculoskeletal system. CIMA has developed an innovative graduate training programme and undertaken well-received public engagement activities. The revised CIMA strategy will be increasingly translational, but informed by basic research. Specifically, we will; determine how epigenetic changes in the ageing musculoskeletal system influence the risk of musculoskeletal disorders, the effect of modification of epigenetic changes on musculoskeletal function, and the effect of lifestyle changes on epigenetic marks and molecules; design and implement interventions based on physical activity, nutrition, anti-inflammatory or age-retarding agents on decline of the ageing musculoskeletal system; extend the CIMA training programme to increase MRes, PhD and clinical training, and; develop engagement and impact activities to increase involvement of patients and the older population, and work with industry and other partners to maximise translation of our research discoveries. Finally, it will provide a resilience that will ensure musculoskeletal ageing moves to the centre of medical research activities within and beyond the UK.

CIMA renewal will contribute to all key impacts, including advancement of scientific knowledge, health and wellbeing, economic competitiveness, policy development and the provision of skilled people to the workforce. Our activities will supplement and complement existing programmes, harnessing the best practice at each of the centres to deliver excellence at all. In every area, the process will be a dialogue or platform of co-discovery, where both sides benefit from improved knowledge and understanding.

Benefits are targeted to the aging population and those who have conditions that are associated with accelerated ageing, for example those with systemic and local joint inflammation.

Potential impacts to the ageing population from advances in scientific knowledge include:
- direct benefits including learning and empowerment from contributing to the design and delivery of studies
- Improved ability to monitor age-related decline of the entire musculoskeletal system and the effects of potential interventions to reduce this through use of the CIMA Toolkit
- benefits from involvement in effective shared decision making using tools like FRAX for assessing fracture risk.
- wider understanding of musculoskeletal ageing from PPI and patient engagement, VOICENorth (Quote: 'We are volunteering the accumulated knowledge we have gathered over our entire life'.)
- better information about healthy ageing and how to achieve it from better trained experts and improved personal engagement from platforms including VOICENorth online and the MOOC.- enhanced understanding of mechanisms and targets, feeding directly into accelerated novel drug identification and development
- refining outcomes and delivering interventions that improve care and both scientific and clinical practice

Impacts for health and wellbeing include:
- improved pain, function and quality of life from participation in clinical trials and accruing to the wider population once interventions are proven effective
- high standard of care related to being involved in a clinical trial
- avoidance of harm from better targeting of therapy and toxicity identification of widely used drugs, such as paracetamol
- improved treatment options and prognostication

Impacts on economic competitiveness include:
- investment in research, delivering economic benefits for the centre and wider economy by a) health gains net of the cost of delivery, b) GDP gains from the activity and further stimulated activity
- these will come from new biomarkers, assessment tools, nutritional supplements and drugs, training and engagement activity

Impacts on policy development will include:
- benefits of more effective care, driven by NICE and other guidelines
- briefing MPs; advising expert panels, select committees, the Foresight programme (such as 'Future of an Ageing Population', 2016); WHO
- collaboration and advisory work for industry, including the CIMA Industrial Strategy Board

Impacts on provision of skilled workforce will include:
- better education and proactive identification of talented scientists from early identification and support for innovation from school sixth form onwards
- enhanced awareness of musculoskeletal ageing in trainee scientists and clinicians arising from exposure to the CIMA MOOC
- support for MRes and PhD students, postdoctoral and tenured scientists, who will contribute to training the next generation, specifically training to increase understanding of PPI and engagement.
- closer industry links leading to both funding of education and scientific posts by industry and flow of highly skilled workforce between academia and industry