CIMA: The Centre for Integrated Research into Musculoskeletal Ageing

Objectives
This proposal will bring together researchers from 3 leading UK Universities to establish a Centre of Excellence that will undertake world-leading research to understand why our bones, joints and muscles function less well as we age and why older people develop clinical diseases of bones, joints and muscles, such as arthritis or osteoporosis. The Centre will also investigate new ways of preventing the deterioration of bones, muscle and joints that occur as we age to help preserve mobility and independence in older people.

Clinical Benefits
Understanding why our bones, joints and muscles function less well as we get older is crucial to improving ways of preventing the decline in musculoskeletal function that occurs in older people and to an understanding of why older people develop diseases such as osteoporosis or arthritis. Our work aims to develop ways of preventing ageing-related changes in bone, joints and muscle which will be acceptable, cost effective and sustainable for everyone who could benefit from them. This will lead to major improvements in the quality of life of older people associated with increased mobility, greater opportunity for independent living and a decreased risk of developing clinical disorders of bones and joints.

Questions: This application will bring together outstanding researchers from the Universities of Liverpool, Newcastle and Sheffield to undertake innovative and integrated studies of the whole musculoskeletal system. These groups have previously studied individual tissues, but will combine together in this innovative Centre to find answers to a number of important questions:
1. What are the common mechanisms that underlie the age-related deterioration in function of joints, bone, tendon, ligaments and muscle?
2. What is the best way of assessing the changes in structure and function of joints, bone, tendons, ligaments and muscle during ageing and how can we develop an integrated approach to assessing the function of the whole musculoskeletal system?
3. What is the best way of assessing whether a treatment can prevent the loss of function of the whole musculoskeletal system during ageing and how can we determine whether an intervention will reduce the risk of musculoskeletal disorders?
4. Which interventions based on changes in physical activity, improved nutrition or drug-based approaches are effective in preserving musculoskeletal function in older people?

Experimental plan: CIMA will:
1. Integrate existing basic science studies on single tissues to study the whole musculoskeletal system. This will bring unique expertise and equipment to identify common mechanisms leading to age-related decline in musculoskeletal tissues. This research will identify new targets for interventions to slow age-related decline in musculoskeletal tissues.
2. Examine different methods to monitor the structure and function of musculoskeletal tissues and develop an integrated assessment of age-related decline in the whole system.
3. Study the changes in the musculoskeletal system in healthy older people and in patients with disorders of musculoskeletal tissues to identify which groups will provide the most information for studies of interventions.
4. Devise new therapies to prevent age-related decline of musculoskeletal tissues based on types of exercise that improve bone, tendon, ligament and muscle function without damaging joints, improved nutrition or new drugs.
5. Train to the highest standard new researchers to increase capacity to address musculoskeletal ageing.

Novelty:
The work of the Centre will be novel in bringing together to address a common problem, the expertise and facilities currently in 3 Universities. It will identify new common mechanisms underlying age-related loss of function of bone, joints, tendons, ligaments and muscle that may provide routes for possible new drug interventions.

The Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between centres of excellence at the Universities of Liverpool, Newcastle and Sheffield that brings together complementary expertise in skeletal muscle, bone, cartilage and tendon biology, ageing research, nutrition and exercise interventions and clinical excellence in musculoskeletal disorders. CIMA will develop an integrated approach to understanding the processes and effects of ageing in tissues of the musculoskeletal system, how ageing contributes to diseases of the musculoskeletal system and how these processes may be ameliorated or prevented. The three Institutions have developed a strong framework for collaboration and CIMA will provide an outstanding scientific environment that gives researchers access to excellent facilities, cohorts and techniques and will develop a high quality training programme to improve and expand UK and International research capacity in musculoskeletal ageing. A unique feature of CIMA research will be its focus on the whole musculoskeletal system rather than on individual tissue components. We will integrate basic science programmes to understand how intrinsic mechanisms of ageing lead to decline in musculoskeletal function and contribute to musculoskeletal disorders, identify and share current state-of-the-art in monitoring age-related changes in individual musculoskeletal tissues and provide an integrated assessment of musculoskeletal function through use of modelling and systems biology approaches. We will also develop and test novel approaches to reduce age-related deterioration of the musculoskeletal system through nutrition, exercise and pharmacological interventions.

Who will benefit from this research?
Older people will be the main beneficiaries. Improving the health and quality of life of ageing populations is a major challenge. Projections from the UK Office for National Statistics & Government Actuary Department indicate that by 2050 the proportion of people over 60 in Britain will rise from 21% to ~40%. Decline in musculoskeletal function is a major contributor to health problems in older people. UK industry's pharmaceutical and personal care products sectors will benefit from research which will provide resources to guide development of effective interventions to reduce age-related changes in the musculoskeletal system. With the increasing older population there is demand for anti-ageing products with substantial economic potential for the pharmaceutical and personal care products sectors and improved quality of life for older people. The UK research community will benefit through increased critical mass, new techniques, researcher training and CIMA taking a leading role in national and international research activities in this area.

How will they benefit from this research?
CIMA will identify interventions to reduce age-related decline in the musculoskeletal system. Current recommendations promote physical activity, but there are no validated nutritional, exercise or pharmacological approaches to maintain health of the whole musculoskeletal system during ageing that are demonstrated to be effective and acceptable to target population groups and sustainable. We will develop, pilot and test interventions with widespread benefit for public health to improve mobility, independence and quality of life and with an economic impact through reducing healthcare costs. UK pharmaceutical companies will benefit from the work of CIMA in identifying and validating biomarkers, trial design and therapeutic targets.

What will these impacts be, and what is their importance?
The CIMA programme will identify new intervention targets and optimise interventions to preserve musculoskeletal health, reduce the need for assisted care and enhance quality of life in older people (5-10 years).

CIMA will identify new biomarkers for assessing musculoskeletal ageing and for assessing the impact of interventions to improve musculoskeletal health in older people (5-10 years).

Through direct public engagement and interaction with organisations including Age UK and Arthritis Research UK, CIMA will disseminate findings to the general population by routes including web-based information, flyers and training for health professionals (5 years).

CIMA will expand research capacity by training researchers and clinicians with multidisciplinary skills in ageing research and musculoskeletal biology that are applicable to multiple employment sectors (5 years).