Combating hypothalamic ageing through exercise

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It is popularly accepted that the way to a long life is through regular exercise, good sleeping habits and a healthy diet. Indeed, regular exercise is beneficial for the brain and body and can help us lose fat, repair the brain, stimulate the production of new brain cells, improve our problem solving abilities, and strengthen our body clock. A key to having good sleep and dietary habits is to make sure that we maintain regular bed-times and meal times. Daily regularity in sleeping and feeding arises because our body clock, which tells us when to awaken and when to eat, is matched to the 24h changes in daylight. Unfortunately, as we age, both our body clock and our synchronization to the external world can weaken, resulting in disruptions in sleep-wake cycle, eating and impaired problem-solving abilities. In people leading sedentary lifestyles, such disruptions worsen and the ageing process is sped up, leading to premature death. This is called 'unhealthy ageing' and recently we have found similar effects in sedentary mice. Maintaining mice in social groups but without a means to exercise, results in these animals becoming obese in old age. They also have poor control of their eating and resting habits and weakened body clocks. Remarkably, when provided with an exercise wheel, these mice choose to vigorously run in the wheel and, within 6 weeks, they lose 8% of their body weight. This suggests that negative aspects of a sedentary lifestyle may be corrected by exercise in old age. Unfortunately, we do not understand how this change in lifestyle affects the activity of brain cells that control the body clock and food consumption. We also lack knowledge of how exercise may regulate body fat levels in old animals and we do not know if brain repair, new brain cell production and problem-solving performance in these mice are affected by exercise in old age. Further, we do not know if adopting an active lifestyle in young or middle adulthood can prevent subsequent age-related obesity, body clock disruption, and decline in decision-making. Whether regular exercise can slow-down the ageing process in animals with body clocks weakened through loss of a key signaling chemical is also not known.In this research, we aim to study how providing mice with the opportunity to voluntarily exercise in a wheel at different stages of life thwarts the ageing process. We anticipate that the younger the animals are when they begin exercising, the more effectively the abnormal ageing process will be lessened. It is possible that even after spending half their life in a sedentary state that animals will show a significant improvement in their brain and body functions following the opportunity to exercise. Animals with weakened or completely dysfunctional body clocks are potentially prone to accelerated ageing and we will explore whether exercise is an effective intervention in these animals. It is also possible that regular exercise will stimulate the ageing brain to produce new cells and improve problem-solving capabilities. Through this research project, we will establish new ways of restoring brain and body rhythms to promote good health and longevity.