The rationale of the Centre for Musculoskeletal Ageing Research (CMAR) was, and remains that multidisciplinary research, at scale, is required if we are to achieve meaningful impact. CMAR was thus set up as a partnership between the universities of Birmingham and Nottingham uniting the significant research strengths of both partners in musculoskeletal (MSK) physiology, metabolism, neurophysiology, endocrinology, inflammation biology, and motivational psychology and in recognition of our ability to deliver interventions in human populations. In the first 5 year phase (2012 to 2017), we focused on improving understanding of the loss of (MSK) mass and metabolic and contractile function with age, with an emphasis on muscle.
We also had research themes considering the role of the central nervous system in loss of muscle function and strength and compromised motor control and balance. Both of these have allowed us to develop interventions to overcome the negative impact of age, using physical activity and nutritional approaches predominantly, but also methodologies such as brain stimulation to improve motor control.
More recently we have been working with biomedical engineers to develop novel scaffolds for cartilage and bone repair. In addition, the inclusion of metabolomics as a theme following the inception of the Centre, facilitated by the establishment of the Birmingham Phenome Centre (funded via an MRC Clinical Infrastructure Award), has allowed CMAR to begin untangling the impacts of ageing and lifestyle on metabolic health. This has allowed us to identify biomarkers for predicting the response to therapy in patients with rheumatoid arthritis, and other age-related MSK diseases. This approach, married with our cutting-edge tracer based techniques of tissue and substrate turnover and world-leading MR imaging and spectroscopy facilities, offered an unprecedented opportunity for human ageing research going forward, which we will transition from “physiological ageing” to MSK disease to give greater patient benefit.
Finally, in phase 1 we included motivational psychology in our multidisciplinary working, recognising that advances in tackling MSK conditions, which include a significant emphasis on lifestyle, need a solid theoretical framework to design and implement programmes that will achieve significant uptake and adherence by older adults. We have known since the time of Hippocrates that “Walking is man’s best medicine” but a majority of adults have not adopted an active lifestyle.
In phase 1 integrated working across both sites and increased multidisciplinary research capacity in our priority thematic areas was achieved in a variety of ways:
1) Two new academic staff were appointed at the University of Birmingham and 2 postdoctoral fellows at the University of Nottingham. The former bringing expertise in interventions in frail elders and experimental medicine in MSK ageing and disease, and the latter to support the development of the stable isotope tracer platform and provide genomics and technical support. A total of 16 further appointments were made by the host institutions, showing a sustained commitment to the Centre;
2) Existing researchers established in their field repositioned some of their activity to include ageing. This meant that CMAR acquired excellence, depth and breadth to its research. The impact was to produce significant leverage and increase visibility of ageing research: Birmingham re-organised its Life Sciences capability to include an Institute of Inflammation and Ageing and an Institute of Translational Medicine which now houses the CMAR administrative office; it made Exercise as Medicine a priority for university PhD studentships and most recently committed £25m to a Centre for Human Brain Health that will have Motor Control as one of its 3 research themes. At Nottingham a similar effect was seen with MSK Health in Ageing and Wellbeing selected as a Research Priority Area (aligning CMAR and the ARUK Pain Centre, ARUK Centre for Sport, Exercise and OA and the Nottingham and Derby applied health research group in the care of older people); there has been significant further investment to establish the Sir Peter Mansfield Imaging Centre (SPMIC), a multidisciplinary translational imaging centre, funded in part by the MRC-led Clinical Research Capabilities and Technologies Initiative, providing both quantitative and functional MRI and MRS techniques for probing MSK ageing, including in-bore exercise capabilities;
3) We devoted funds to PhD studentships, which were matched by the host institutions. This set up a cadre of 14 students who met regularly at workshops and whose ranks have been increased by further internally and externally funded studentships, including BBSRC, EPSRC, MRC and Wellcome Trust DTPs and a Marie Curie ITN.
Integrated working has been achieved gradually and is still a work in progress, both within each campus as well as across the two sites. As researchers at the two universities had not worked together to any extent prior to the award of the Centre, a series of workshops were held at the start and in the first 3 years to share interests, resources and skills. One specific workshop in year 1 generated ideas for PhD projects which then allowed researchers to bid for the Centre studentships. Once awarded these then helped to establish new within site and cross-site collaborations.
The Management Board also played a key role in ensuring cross-site working was achieved. It has representation by academics from both institutions and in the first 18 months met every 2 months, though the director and deputy were in more frequent contact. The board helped by raising awareness of activity on both sites (such as seminar series, we are close enough for attendance to be feasible) and ensuring we were all aware of opportunities to secure further funding or work together. The Centre administrator played a vital role as a key communication conduit and point of contact for researchers on both sites.
CMAR Forward Strategy
In phase 1 we established well-functioning structures and platforms that are providing research impact focussed on age-related loss of MSK function that will have significant clinical consequences. We recognised however that if we were to maximise medical advance and patient benefit, then we also needed to consider the influence of ageing on the pathogenesis of disease-related MSK decline.
There are 6 million people with osteoarthritis (OA) in the UK, a painful condition which reduces the ability to work and has a significant impact on quality of life. OA is exacerbated by obesity and there are currently no treatments other than pain remediation and eventually joint replacement.
At the end of phase 1, we were in a position to apply the expertise of CMAR to the role that ageing processes play in OA and RA pathogenesis and potentially open up new therapeutic pathways, based upon inhibiting core ageing processes. Such a proposition would have seemed unrealistic even 5 years ago, but drugs that inhibit ageing by for example mimicking dietary restriction, or promoting autophagy, have shown promise in animal models and are now in clinical trials. These drugs could well have efficacy in MSK conditions. Similarly, applying CMAR expertise to other age-related diseases where frailty, sarcopenia and weakness prevail (such as COPD, IBD and ICU trauma patients) will have a significant impact.