Combating hypothalamic ageing through exercise

通过运动对抗下丘脑衰老

• 批准号: BB/R019223/2
• 负责人: Hugh Piggins
• 金额: $ 67.7万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR019223%2F2
• 关键词: Combating; hypothalamic; ageing; through; exercise

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.

有规律的锻炼、良好的睡眠习惯和健康的饮食是长寿之道，这是人们普遍接受的观点。事实上，定期锻炼对大脑和身体有益，可以帮助我们减掉脂肪、修复大脑、刺激新脑细胞的产生、提高我们解决问题的能力并增强我们的生物钟。拥有良好睡眠和饮食习惯的关键是确保我们保持规律的睡觉时间和吃饭时间。每天睡眠和进食的规律性是因为我们的生物钟，它告诉我们什么时候醒来，什么时候吃饭，与白天24小时的变化相匹配。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。对于那些久坐不动的人来说，这种干扰会恶化，衰老过程会加快，导致过早死亡。这被称为“不健康的衰老”，最近我们在久坐不动的老鼠身上发现了类似的效果。将小鼠保持在社会群体中，但没有锻炼的手段，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，这些小鼠选择在轮子上剧烈奔跑，在6周内，它们失去了8%的体重。这表明，久坐不动的生活方式的负面影响可以通过老年锻炼来纠正。不幸的是，我们不知道这种生活方式的改变如何影响控制生物钟和食物消耗的脑细胞的活动。我们也缺乏关于运动如何调节老年动物体内脂肪水平的知识，我们不知道这些小鼠的大脑修复，新脑细胞的产生和解决问题的能力是否受到老年运动的影响。此外，我们不知道在年轻或中年时采取积极的生活方式是否可以预防随后的年龄相关性肥胖，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是未知的。在这项研究中，我们的目标是研究在生命的不同阶段为小鼠提供自愿在轮子上锻炼的机会如何阻止衰老过程。我们预计，当动物开始锻炼时，它们越年轻，异常衰老过程就越有效地减少。有可能的是，即使在久坐不动的状态下度过了一半的生命，动物在有机会锻炼后，其大脑和身体功能也会显着改善。生物钟减弱或完全失调的动物可能容易加速衰老，我们将探讨运动是否是对这些动物的有效干预。定期锻炼也有可能刺激衰老的大脑产生新细胞并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奏的新方法，以促进健康和长寿。

项目成果

Timed daily exercise remodels circadian rhythms in mice.

• DOI: 10.1038/s42003-021-02239-2
• 发表时间: 2021-06-18
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Hughes ATL;Samuels RE;Baño-Otálora B;Belle MDC;Wegner S;Guilding C;Northeast RC;Loudon ASI;Gigg J;Piggins HD
• 通讯作者: Piggins HD

Circadian VIPergic Neurons of the Suprachiasmatic Nuclei Sculpt the Sleep-Wake Cycle.

• DOI: 10.1016/j.neuron.2020.08.001
• 发表时间: 2020-11-11
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Collins B;Pierre-Ferrer S;Muheim C;Lukacsovich D;Cai Y;Spinnler A;Herrera CG;Wen S;Winterer J;Belle MDC;Piggins HD;Hastings M;Loudon A;Yan J;Földy C;Adamantidis A;Brown SA
• 通讯作者: Brown SA

A new phase model of the spatiotemporal relationships between three circadian oscillators in the brainstem.

• DOI: 10.1038/s41598-023-32315-y
• 发表时间: 2023-04-04
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Ahern, Jake;Chrobok, Lukasz;Champneys, Alan R.;Piggins, Hugh D.
• 通讯作者: Piggins, Hugh D.

Phasic Neuronal Firing in the Rodent Nucleus of the Solitary Tract ex vivo.

• DOI: 10.3389/fphys.2021.638695
• 发表时间: 2021
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: Chrobok L;Wojcik M;Klich JD;Pradel K;Lewandowski MH;Piggins HD
• 通讯作者: Piggins HD

Circadian Influences on the Habenula and Their Potential Contribution to Neuropsychiatric Disorders.

昼夜节律对Habenula的影响及其对神经精神疾病的潜在贡献。

• DOI: 10.3389/fnbeh.2021.815700
• 发表时间: 2021
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Young CJ;Lyons D;Piggins HD
• 通讯作者: Piggins HD