Examining the impact of inactivity and diet on muscle health with age in C. elegans

检查不活动和饮食对秀丽隐杆线虫肌肉健康随年龄增长的影响

• 批准号: BB/S002863/1
• 负责人: Nathaniel Szewczyk
• 金额: $ 41.41万
• 依托单位: University of Nottingham
• 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%2FS002863%2F1
• 关键词: Examining; impact; inactivity; diet; muscle

Intuitively we know that lack of physical activity makes us feel both mentally and physically worse. We also appreciate that as we get older we become less active and less healthy. Surprisingly, the World Health Organization has found that inactivity does indeed cause poorer health and that, in fact, it is the fourth leading cause of death worldwide. Despite the importance of inactivity on poor health, the majority of research on how inactivity causes poor health has been conducted in astronauts (e.g. less than 900 individuals worldwide since the 1960s!). Currently allot of research is conducted on the impact of activity on health with the assumption that the mechanisms that promote health in response to activity are the same ones that promote lack of health with inactivity. However, loss of muscle in response to spaceflight or confinement to bed is rapid and large (>7% loss in 7 days, a dramatic decrease in 1 week) whereas increase in muscle in response to exercise is much slower (nobody gets fit in just 1 week at the sports centre). Thus, research into how inactivity causes poor health is needed and needed quickly. In order to gain this knowledge faster, we propose to study how inactivity causes poor health in a tiny worm and later to test if the same mechanisms act in people. This may seem far fetched but we have already shown that the muscles of this tiny worm respond to spaceflight much the same way astronauts muscles do, with many changes in the molecules that cause much to be strong and make energy declining rapidly in both the worm and in astronauts. Our past spaceflight work has suggested that decreased signal from nerve to muscle occurs in spaceflown worms and similar changes are seen in people confined to bed. Therefore we will systematically decrease signal from nerve to muscle in worms and determine the impact upon health and particularly muscle health decline with age. We will specifically ask: i) Does it matter when you are inactive (e.g. child vs. adult) in terms of the impact on health and muscle health decline with age; ii) Do repeated episodes of inactivity during adulthood (e.g. working at a desk, hospitalization, etc) have additive negative impacts on health and muscle decline with age; and iii) Can diet which produces increased health (e.g. longer life) protect against the impact of inactivity? The results of these experiments will allow us to begin to understand the molecules that control these processes and, in the future, possibly design new drugs. Equally importantly, the results from these experiments will provide a framework for testing if the findings from the worm also hold true in people but in a faster and cheaper way than starting with studying people (much as we used animals to prove spaceflight was safe before sending astronauts).

直觉上，我们知道缺乏体育活动会让我们在精神和身体上都感觉更糟。我们也意识到，随着年龄的增长，我们变得不那么活跃和健康。令人惊讶的是，世界卫生组织发现，不活动确实会导致健康状况恶化，事实上，它是全球第四大死亡原因。尽管不活动对健康状况不佳的重要性，但大多数关于不活动如何导致健康状况不佳的研究都是在宇航员中进行的（例如，自20世纪60年代以来，全球不到900人！）。目前，许多研究都是关于活动对健康的影响，假设促进健康的机制与促进缺乏健康的机制是相同的。然而，由于航天飞行或卧床而导致的肌肉损失是迅速而巨大的（7天内损失>7%，1周内急剧下降），而由于运动而增加的肌肉则要慢得多（在体育中心，没有人在1周内就能恢复健康）。因此，研究不活动如何导致健康状况不佳是必要的，而且需要迅速。为了更快地获得这一知识，我们建议研究不活动如何导致微小蠕虫的健康状况不佳，然后测试是否有相同的机制作用于人类。这似乎有些牵强，但我们已经证明，这种微小蠕虫的肌肉对太空飞行的反应与宇航员的肌肉反应大致相同，分子中的许多变化导致蠕虫和宇航员的能量迅速下降。我们过去的太空飞行工作表明，从神经到肌肉的信号减少发生在太空飞行的蠕虫身上，类似的变化也发生在卧床不起的人身上。因此，我们将系统地减少蠕虫从神经到肌肉的信号，并确定对健康的影响，特别是肌肉健康随年龄的下降。我们将具体询问：1.当你不活跃时，（例如儿童与成人）在对健康和肌肉健康的影响方面随年龄下降; ii）在成年期反复发生不活动（例如，在办公桌前工作，住院治疗等）对健康和肌肉随着年龄的增长而衰退有附加的负面影响;和iii）能增进健康（例如延长寿命）的饮食是否能防止不活动的影响？这些实验的结果将使我们开始了解控制这些过程的分子，并在未来可能设计新的药物。同样重要的是，这些实验的结果将提供一个框架，用于测试蠕虫的发现是否也适用于人类，但比从研究人类开始更快，更便宜（就像我们在发送宇航员之前使用动物来证明太空飞行是安全的一样）。

项目成果

Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans.

• DOI: 10.1002/jcsm.12843
• 发表时间: 2022-04
• 期刊: Journal of cachexia, sarcopenia and muscle
• 作者: Gharahdaghi N;Rudrappa S;Brook MS;Farrash W;Idris I;Aziz MHA;Kadi F;Papaioannou K;Phillips BE;Sian T;Herrod PJ;Wilkinson DJ;Szewczyk NJ;Smith K;Atherton PJ
• 通讯作者: Atherton PJ

Commercial access for UK/ESA student experiments on board the ISS

英国/欧空局学生在国际空间站上进行实验的商业访问

• 发表时间: 2020
• 作者: Gaffney, CJ

Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model.

• DOI: 10.1073/pnas.2018342118
• 发表时间: 2021-03-02
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Ellwood RA;Hewitt JE;Torregrossa R;Philp AM;Hardee JP;Hughes S;van de Klashorst D;Gharahdaghi N;Anupom T;Slade L;Deane CS;Cooke M;Etheridge T;Piasecki M;Antebi A;Lynch GS;Philp A;Vanapalli SA;Whiteman M;Szewczyk NJ
• 通讯作者: Szewczyk NJ

Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age.

• DOI: 10.1007/s11357-022-00658-5
• 发表时间: 2023-06
• 期刊: GEROSCIENCE
• 影响因子: 5.6
• 作者: Deane, Colleen S.;Phillips, Bethan E.;Willis, Craig R. G.;Wilkinson, Daniel J.;Smith, Ken;Higashitani, Nahoko;Williams, John P.;Szewczyk, Nathaniel J.;Atherton, Philip J.;Higashitani, Atsushi;Etheridge, Timothy
• 通讯作者: Etheridge, Timothy

Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.

年轻人和老年人废用性肌肉萎缩与抗阻运动引起的肥大的转录组荟萃分析。

• DOI: 10.1002/jcsm.12706
• 发表时间: 2021-06
• 期刊: Journal of cachexia, sarcopenia and muscle
• 作者: Deane CS;Willis CRG;Phillips BE;Atherton PJ;Harries LW;Ames RM;Szewczyk NJ;Etheridge T
• 通讯作者: Etheridge T