Centre for Musculoskeletal Ageing Research

Ageing is a complex process that results in the reduced functioning of most of the body's organ systems, with the musculoskeletal system (muscle, bone, tendon and cartilage) significantly affected. The musculoskeletal system is compromised not only by loss of muscle, bone and cartilage with age, but also by the decline in function of the nervous system which results in reduced control of movement and balance. Ageing is also often accompanied by weight gain which puts further strain on joints and contributes to erosion of cartilage and bone, increasing the chances of developing Osteoarthritis (OA). Importantly both ageing and obesity decrease physical activity levels and increase the level of inflammation in the body and alter hormone balance, all of which affect the ability of the body to maintain the musculoskeletal system. Therefore increased physical activity and interventions that are able to reduce inflammation and correct age and obesity related hormone changes, offer a way forward for delaying age-related changes in the musculoskeletal system.
Objectives:
The objective is to set up a Centre of Excellence in Musculoskeletal Ageing Research by integrating and expanding the complementary research and postgraduate training activity of the two leading Midlands based Universities, Birmingham and Nottingham, together with their associated NHS hospital trusts. The Centre will also establish a unique technical facility for measuring human muscle, tendon and bone metabolism that will provide a valuable resource for the UK research community. The Centre's over-arching research aim is to understand how ageing results in loss of musculoskeletal function and to use this knowledge to intervene and minimise age-related musculoskeletal decline and disease. The major focus of these interventions will be exercise and diet.

Clinical benefits:
The potential clinical benefits of the research carried out by the Centre are significant as age-related loss of musculoskeletal function has major clinical consequences, including increased risk of falls and fracture (hip and wrist), OA and pain. 1 in 3 older adults fall each year and for 76,000 patients this results in hip fracture. Hip fracture is associated with increased morbidity, loss of independence and the 1 year mortality figure for hip fracture is 22%. There are 6 million people with OA in the UK1, a painful condition which reduces the ability to work and has a significant impact upon quality of life. OA is exacerbated by obesity and there are currently no treatments other than pain remediation.

Research questions:
1. What are the key factors driving ageing of the component tissues of the musculoskeletal system, both individually and as an integrated system? This will include the role of genetics and lifestyle; the role of inflammation, physical activity and changes in tissue steroid hormones; age-related loss of neuromuscular function and its contribution to reduced coordination, balance and reduced ability to perform complex motor tasks such as driving.
2. Assessment of interventions to improve musculoskeletal function in old age. It is well established that physical activity reduces the loss of muscle and bone mass with age. In young subjects dietary supplements can increase muscle mass, improve metabolism and reduce inflammation, but efficacy in older adults is largely unknown. The Centre will determine optimal exercise and nutritional supplementation regimes for musculoskeletal maintenance in older adults, both healthy and frail. Interventions will also include pharmacological approaches aimed at reducing inflammation and adjusting hormone balance in favour of musculoskeletal maintenance.
3. Identifying psychological and environmental (practical) barriers to increased physical activity or weight loss in older adults will be a key question addressed by the Centre, with the aim of developing interventions that will be practical and attractive to older adults.

Centre research will be carried out almost entirely in humans, with animal studies limited to testing of new hypotheses or treatments.
1. Understanding the processes underlying the loss of muscle, bone and cartilage with age, the role played by inflammation, metabolism and altered hormones and the efficacy of a range of methods for improving musculoskeletal function, will be addressed using a variety of methods in healthy older adults. This will include:
a. Analysis of new and stored muscle biopsy material, including samples from a 20 year longitudinal tissue bank;
b. Studies of muscle function and metabolism in older humans during exercise;
c. Computer modelling of these data to understand the key factors driving musculoskeletal decline and revealing where interventions should be targeted to gain maximum benefit;
d. Studies of neuromuscular function using lab based analysis of feedback from the brain to the muscles and novel blue-tooth technology to analyse gait in volunteers whilst carrying out their normal activities.

2. Intervention studies to improve musculoskeletal function will include:
a. Assessing the efficacy of different diet and exercise regimes. To improve adherence to these protocols, different motivational approaches will be assessed in older volunteers.
b. Assessing the benefits of novel drugs;
c. Virtual reality and augmented muscle activation (electromagnetic stimulation) to improve neuromuscular performance.

3. Overcoming barriers to lifestyle change adoption.
Effecting long term lifestyle changes remains a significant health challenge. A unique feature of this Centre will be close working with psychologists in order to understand and optimise motivational processes linked to increased physical activity or weight loss. The focus will be on development, implementation and evaluation of theory-based psychological interventions in older adults, initially community dwelling but eventually extending to residential home settings.

370,000 older adults fall each year in the UK, 76,000 of these falls result in hip fracture and this is predicted to rise to 120,000 by 2015. There are also 6 million UK patients with osteoarthritis. These are just two examples of the consequences of unsuccessful musculoskeletal ageing. The proposed Centre for Musculoskeletal Ageing Research will improve understanding of the loss of musculoskeletal mass and function with age. Crucially, it will use this knowledge to develop and validate evidence-based interventions, with a focus on physical activity and diet, for use in the community as well as care or residential homes, which will attenuate age-related musculoskeletal frailty.
The potential beneficiaries and areas of impact of the research include:
a. Older individuals and their carers will benefit, through extended independence and good health of the older individual. In the case of falls, hip fracture is a leading cause of admission into residential care as well as leading to increased mortality. Relatives lose out economically through reduced time spent at work whilst caring for the injured relative. Maintaining good musculoskeletal function will help to prevent primary and secondary falls and reduce the chance of hip fracture. The two most significant risk factors for Osteoarthritis are age and obesity and OA has a significant economic impact through costs to the NHS and for loss of productivity for the patient. Research in the Centre will develop interventions to optimise musculoskeletal function into old age, helping to prevent the incidence of both conditions and influencing health policy in the UK. Maintained physical vitality and independence will also have broader health benefits, contributing to maintenance of well being.
b. UK economy. According to ARUKs 2008 Arthritis in the UK factsheet 10 million working days were lost through musculoskeletal conditions in 2006/7 and the cost to the NHS of poor musculoskeletal health is £5.7 billion per annum. maintaining musculoskeletal function in old age will thus have impact on the cost of health care in the UK and beyond;
c. Pharmaceutical and nutraceutical industry. The interventions tested in the Centre will include pharmacological interventions and will potentially extend the remit of existing drugs or those in development by big pharma. Equally interventions involving nutraceuticals should provide a strong evidence base for their use in older adults, thus helping this industry.
d.Public and private organisations providing advice and services to older adults (NHS, AGE UK, BUPA), will benefit through the availability of a strong evidence base for health policy or interventions (lifestyle, nutraceutical or pharmacology based). Centre research will also include a strong motivational psychology element, assessing which lifestyle intervention delivery modes achieve greater adherence in older adults;
e. Understanding of musculoskeletal development and ageing and the impact of exercise and nutrition, will be improved and will increase the knowledge ase and research and training capacity in a key area in the UK.