Centre for Musculoskeletal Ageing Research

Research context: We are living longer but not healthier, with adults in the UK on average now spending the last decade of life in poor health. Decline in our musculoskeletal system (muscle, bone, cartilage and tendon), and diseases of the joints such as Osteoarthritis (OA) and Rheumatoid Arthritis (RA), are major contributors to ill health in old age. The annual cost to the NHS of musculoskeletal decline is over £5 billion. Doing nothing about the current situation is an expensive and untenable option.
The Centre for Musculoskeletal Ageing Research aims to understand the age-related loss of musculoskeletal function and the role played by lifestyle (physical inactivity and obesity) in influencing this process. Physical activity and diet-based interventions are tested by the Centre to ensure these are effective in older adults. The Centre also includes motivational psychology research to develop approaches that encourage people to adopt healthy lifestyles.

Aims and objectives:
In the second 5 years of the Centre the research will expand to investigate the processes that cause a person to progress from healthy old age to developing arthritis. This will open up new ways to prevent and treat arthritis.
The objectives of the Centre are:
1. To increase understanding of the processes influencing the rate of ageing of the musculoskeletal system and how these increase susceptibility to frailty and disease;
2. To develop and test interventions to improve musculoskeletal health;
3. To develop strong national and international networking to create a significant Healthy Musculoskeletal Ageing research, training and dissemination facility;
4. To increase use of existing patient cohorts and data to support our aims;
5. To work with key policy and health practice influencers, industry and PPI groups to find routes to translation of our research in to health benefits.

Potential applications and benefits:
The potential benefits of the research carried out by the Centre are significant as age-related loss of musculoskeletal function has major health consequences and reduced ability to stay in employment and maintain independence. Applying the knowledge we acquire to understanding the link between ageing and the development of arthritis will increase the impact of our work further, potentially revealing novel routes to the prevention or treatment of arthritis. Applying our exercise interventions to those with established disease can help reduce pain and fatigue and improve quality of life.

Contribution to the Arthritis Research UK strategic focus (2015-2020).
The research in CMAR will contribute to the strategic focus of Arthritis Research UK, helping to understand the link between ageing and arthritis and how lifestyle and pharmacological approaches can delay the former to prevent the latter. For example, if Centre research reveals that the processes that drive normal ageing also contribute to the development of arthritis, then some of the new drugs being tested to slow the ageing process may also help prevent development of arthritis, bringing us closer to a Cure. Work on the benefits of exercise for reducing pain and fatigue in adults with OA or RA will transform patient quality of Life. Together the Centre's research programme will thus help meet ARUK's "Prevent, Transform, Cure" strategy.
This summary was drafted with patients in our arthritis PPI group R2P2. They were supportive of research that could give advice on how to exercise safely, fear of making their pain or disease worse with exercise was common. They were supportive of any treatments that could delay or prevent disease, especially drug repurposing. Overall they were supportive and thought it made sense to expand our programme toward disease pathogenesis and to work with other centres to share knowledge. On the subject of PPI group involvement, they suggested that the group supporting the Centre should include healthy elders too, so we will do this

Poor musculoskeletal health has a significant impact upon the economy, society and the individual. The Centre for Musculoskeletal Ageing Research (CMAR) integrates the work of world class researchers, clinicians and health professionals at the Universities of Birmingham, Nottingham and Oxford to focus on understanding:
1. The age-related loss of musculoskeletal mass and function, including the role played by lifestyle (diet, physical inactivity) in influencing the trajectory of this process. Mechanisms such as anabolic resistance, autophagy, neuromuscular decline and cell senescence are key mechanisms being investigated;
2. How ageing influences musculoskeletal disease pathogenesis and frailty. This will include determining: whether ageing is accelerated in Rheumatoid arthritis (RA) and other chronic inflammatory conditions using epigenetic marks indicative of biological ageing, the role of the gut microbiome in musculoskeletal health and disease, the role of anti-inflammatory pathways and their dysregulation in ageing and RA, the factors driving the sarcopaenia secondary to common chronic inflammatory diseases (COPD, IBD) and physical trauma.
3. Physical activity and diet-based interventions will continue to be assessed and validated in healthy elders and patients, ensuring protocols are tailored to adults of differing ability. Metabolomics will be used to help RA patient stratification for therapy and biomedical engineers and neuroscience researchers will test novel methods to improve tissue regeneration and motor control respectively. CMAR will continue to apply its internationally recognised expertise in motivational psychology to develop programmes achieving good adherence in adults, including patients with arthritis and chronic inflammatory conditions.
CMAR will also place emphasis on collaborative working, supporting students and early career researchers to make collaborative visits of up to 1 year to other centres of excellence in the UK or overseas.

Life expectancy in the UK is increasing at a rate of approximately two years per decade; with 1 in 3 children born now expected to reach 100 years. This would be a cause for celebration if it were not for the fact that increases in health span, the years spent in good health, are not keeping pace with lifespan changes. Estimates from the WHO show a 10 year difference between health span and lifespan in the UK. Supporting the continued need for a Centre of Excellence focused on research into musculoskeletal ageing are the dramatic statistics concerning age-related compromise to the musculoskeletal system: 740,000 adults are admitted to A&E each year after a fall, which resulted in 89,000 hip fractures in 2015; 20% of the population consults their GP about a musculoskeletal problem each year and the NHS spends >£5 billion on MSK health; low muscle mass predicts all-cause mortality in older people; arthritis affects over 10 million people in the UK and there are >175,000 joint replacements annually as a result; the indirect cost to the economy of arthritis, in terms of working time lost, is estimated at £14 billion. These figures make it clear that the opportunity to improve the musculoskeletal health of our ageing population is a critical need for a range of key stakeholders.

Academic researchers across a wide variety of disciplines have the opportunity to benefit not only from the new multidisciplinary knowledge produced across our themes of "Mechanisms of musculoskeletal ageing"; "Ageing and the progression to disease and frailty" and "Interventions to improve musculoskeletal health and function", but to access the technical facilities, well-defined patient cohorts and training courses that the Centre will offer.

There will be significant patient benefit from these themes in terms of tackling the conditions outlined above, which do not only affect the elderly but also a significant proportion of younger people, particularly those who have suffered traumatic injury. The approach of the Centre offers not only the potential to develop new approaches to diet and exercise and measure their efficacy in specific populations, where possible directly consulting with patients and using their input to inform developments, but also to develop new pharmaceutical therapies where needed and to work with charities and policymakers to provide the critical evidence and expertise to inform future policy and patient care, as well as to ensure that consistent and well-informed messages are delivered through mainstream media where possible.

Opportunities for economic outputs will arise from the Centre's innovative research programmes, which already benefit from significant industry engagement. New ideas around potential pharmaceutical or dietary approaches can be protected and discussed with industry partners, who can then resource them to reach wider consumers and patients, while smaller firms may wish to partner around the dissemination of new exercise programmes targeted to organisations such as care homes and health services as well as directly to individuals.