The consequences of motor unit remodelling for motor control: an important factor in the loss of mobility with old age.

The muscles in our arms and legs get smaller and weaker in old age, but what is less well known is that the nerves controlling these muscles also undergo dramatic changes. In this research project we will investigate whether the changes occurring in the nerves are related to the general loss of mobility and poor balance that affects frail as well as healthy older people and impacts on the ability to complete physical tasks thereby reducing quality of life and independence in old age.

Each of our muscles has hundreds or thousands of nerves that help us to control movements with each nerve controlling a portion of the muscle, known as motor units which vary in size. For small forces such as used in the majority of daily activities we use the small motor units, giving fine control, while the large units are used only when large forces are needed. Research has shown that more than half of the nerves in a muscle can die by the age of 75 years even during normal, healthy ageing and it tends to be the nerves supplying the large motor units that are affected. However, the nerves that remain, supplying the small motor units, compensate by taking over the portions of the muscle that have lost their connection. This helps to maintain maximal strength but has the disadvantage that when it comes to making the small contractions used for activities such as involving balance, the forces produced may be inappropriate leading to poor motor control, loss of confidence and ultimately a reduction in mobility.

There is some hope, however, because it might be possible to preserve the nerves by leading a physically active lifestyle. We will study the nerves and muscles of people who have maintained exceptionally high exercise levels all of their lives to see whether preservation of nerves is a reason why older athletes are able to maintain remarkable physical activity and performance levels similar to that of young adults. It may also be possible to learn new ways of activating the nerves to generate smooth contractions and we will examine people who have continued dancing into old age.
A limitation in the available scientific data is that up until now almost all of the information we have on the nerve changes during ageing comes from studies of small muscles controlling hands and feet. We will develop the techniques to estimate motor unit size and number in large leg muscles and study frail, healthy and older athletes to see to what extent changes in nerves affect our muscles and the ability to balance and walk.

More than half the motor units in skeletal muscle can be lost by the age of around 75 yrs, but the surviving, predominantly slow, motor units are significantly enlarged. Our interdisciplinary approach will combine clinical and basic sciences to address three main objectives: 1) Assess the extent of motor unit remodelling in the major locomotor muscles of older men; 2) Determine the extent to which motor unit remodelling is associated with difficulty completing daily tasks that are of critical importance for mobility and an independent lifestyle; and 3) Determine whether life-long physical activity modifies either the process of motor unit remodelling or leads to adaptations of neural control that compensate for the motor unit changes.

Frail and healthy older men (n = 100) as well as older dancers and Masters Athletes competing in power and endurance events (n = 30) together with appropriate young controls (n = 80) will be recruited mainly from the large database of participants from our previous European Union-funded studies into ageing. Volunteers will be screened and undergo clinical assessments. Surface and intramuscular electromyography will be used to estimate motor unit size and number in large locomotor muscles. There will be comprehensive assessments of body composition and muscle size using DEXA and magnetic resonance imaging and detailed balance, walking and chair rising tasks. Statistical analysis will examine the motor unit size and number in association with balance and mobility and the extent to which different types of exercise can either preserve the motor units or maintain precise motor control.

This work will be the most comprehensive assessment of motor unit remodelling during ageing to date. It will focus attention onto the motor neurons and motor units and open up new avenues of future research and lifestyle interventions.

Through our well-defined dissemination programme we will communicate the research progression and results to engage stakeholders and anticipate a number of possible impacts:
Scientific community: The greatest impact of this work will be the contribution to scientific understanding of the changes to motor neurons and motor units during ageing, how this relates to general physical capability and how it can be modified through physical activity interventions. Our work will develop novel techniques and a unique dataset that will form the basis from which new hypotheses will be developed.
General public: We will communicate our findings to the general public. It is our experience that older people are very keen to learn of the changes that might affect them during ageing and what can be done to minimise risks. Our work will meet both of these, with the latter point potentially having a lasting impact if we are able to identify a particular type of activity that preserves motor units during ageing that is acceptable for older people. For instance, older people might be reluctant or unable to newly engage in high impact sports, but might be more open to the idea of dedicated activity and balance training through dance or other related activities.
Patient groups: The incidence of sarcopenia, frailty and falls risk is high and is associated with other major disease and can restrict physical activity in older people. Our work to identify appropriate physical activity interventions could be applied to those at risk of developing these health problems. Furthermore, if specific balance training promotes adaptations to better control muscles through rate-coding or alterative recruitment strategies this could be used to rehabilitate those already at high falls risk and poor mobility.
Local and national government and organisations: Promoting active and healthy ageing is high on the agenda for government and other organisations. Decisions must be evidence based and optimise available resources. Our work will help to inform strategies and prescriptions to promote appropriate exercise and lifestyle intervention that could be used by charitable organisations, local and national governments.
Business and the third sector: There are a number of ways in which business, industry and the third sector could exploit the findings from the proposed research. For instance, in the short term there could be a larger market for the provision of exercise or lifestyle intervention for the over 50s. Another possibility is the provision of personalised prescription and recording of activities and rehabilitation of individuals at high risk of falling or deteriorating mobility that could be based on our research findings. An interdisciplinary approach with computer sciences, engineers, clinicians and academics will help fulfil this potential for use in healthcare as well as commercial innovation and this is an area Dr McPhee and colleagues at MMU are already developing. In the longer term, research will help to uncover the molecular pathways leading to motor unit remodelling with ageing and this could lead to pharmacological intervention.