Discovery of brain circuit reversing the decline in physical activity and muscle mass with age

Being physically active is one of the most important things we can do for our physical and mental health and yet, levels progressively decline with age.  Without regular exercise, our muscles decrease in size and get weaker.  This is important because the amount of muscle we have impacts quality of life, overall health and helps resist diseases, like type 2 diabetes and hypertension.  The motivation gap to take up exercise programmes and stick with them has meant the health benefit of exercise is not available for many.  In fact, approximately 40% of UK adults do not take the recommended minimum amount of exercise.  How can we change this?  The goal of this research programme is to identify a fundamental brain circuit controlling the motivation to be physically active.
This programme of research is timely because how much people exercise is a key predictor for health and lifespan.  We started by tracking steps using accelerometers in a group of younger and older UK adults and found the expected reduction in physical activity (PA) and muscle mass, and increase in fat mass in middle-aged compared to younger adults.  We then asked why the motivation to exercise declines with age and turned our attention to brain function because it controls voluntary PA. We next surveyed changes that occur in the brain with age.  A chemical made in our brain called serotonin is known to influence PA.  We then performed a series of studies to support this application.  Specifically, we found a certain subset of cells making serotonin in the brain region called the dorsal raphe nucleus (DRN) change their tone with ageing. We discovered that mimicking this serotonin:DRN tone in young mice produced a middle-aged PA profile.  Importantly, we found that re-tuning the activity of serotonin cells only in this particular part of the brain completely reversed the decline in PA with ageing.  In looking at how this might occur, we...