Combating hypothalamic ageing through exercise

人们普遍认为，长寿的方法是通过经常锻炼，良好的睡眠习惯和健康的饮食。的确，有规律的锻炼对大脑和身体都是有益的，可以帮助我们减掉脂肪，修复大脑，刺激新的脑细胞的产生，提高我们解决问题的能力，增强我们的生物钟。拥有良好睡眠和饮食习惯的关键是确保我们保持规律的就寝时间和用餐时间。我们的生物钟告诉我们什么时候醒来，什么时候吃饭，这与白天24小时的变化是一致的，因此我们每天的睡眠和进食都有规律。不幸的是，随着年龄的增长，我们的生物钟和我们与外部世界的同步都会减弱，导致睡眠-觉醒周期中断，饮食和解决问题的能力受损。在久坐不动的生活方式中，这种破坏会加剧，衰老过程会加速，导致过早死亡。这被称为“不健康的衰老”，最近我们在久坐的老鼠身上发现了类似的影响。将老鼠保持在社会群体中，但没有锻炼的手段，会导致这些动物在老年时变得肥胖。他们对饮食和休息习惯的控制也很差，生物钟也很弱。值得注意的是，当提供一个运动轮时，这些老鼠选择在轮子上剧烈奔跑，在6周内，它们减掉了8%的体重。这表明久坐生活方式的负面影响可以在老年时通过锻炼得到纠正。不幸的是，我们并不了解这种生活方式的改变是如何影响控制生物钟和食物消耗的脑细胞的活动的。我们也不知道运动如何调节年老动物的体脂水平，我们也不知道这些老鼠的大脑修复、新脑细胞的产生和解决问题的能力是否会受到老年运动的影响。此外，我们不知道在青年或中年采取积极的生活方式是否能预防随后的年龄相关肥胖、生物钟紊乱和决策能力下降。对于生物钟因失去一种关键的信号化学物质而变弱的动物来说，定期锻炼是否能减缓衰老过程也尚不清楚。在这项研究中，我们的目标是研究如何为老鼠提供在生命的不同阶段自愿在轮子上锻炼的机会，从而阻止衰老过程。我们预计，当动物开始锻炼时，它们越年轻，异常衰老过程就会越有效地减少。有可能，即使在久坐不动的状态下度过了半辈子的动物，在有机会锻炼之后，它们的大脑和身体功能也会有显著的改善。生物钟变弱或完全失调的动物可能会加速衰老，我们将探索运动对这些动物是否有效。有规律的锻炼也有可能刺激老化的大脑产生新的细胞，提高解决问题的能力。通过这个研究项目，我们将建立恢复大脑和身体节律的新方法，以促进健康和长寿。

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.