Exercise 'prehabilitation': A novel intervention to protect against disuse-induced muscle atrophy and sarcopenia in the old

运动“预康复”：一种新的干预措施，可防止老年人因废用引起的肌肉萎缩和肌少症

• 批准号: BB/N018214/1
• 负责人: Leigh Breen
• 金额: $ 56.54万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN018214%2F1
• 关键词: Exercise; prehabilitation; novel; intervention; protect

Skeletal muscle mass plays an essential role in activities of daily living and regulation of metabolic health. Ageing is associated with a progressive decline in skeletal muscle mass (sarcopenia) that compromises tasks of daily living, metabolic health and increases the risk of falls, fractures and mortality. The healthcare costs associated with treating age-related musculoskeletal decline are vast, and continue to grow with our expanding ageing population. Of concern is that ~30% of those aged 75-84 years suffer from sarcopenia. Thus, interventions to reduce the progression of age-related muscle wasting will improve the quality of life in older individuals and have a profound impact on healthcare expenditure. To place this into context, a 10% reduction in the incidence of sarcopenia would result in an enormous reduction in healthcare expenditure associated with muscle deterioration (estimated annual cost to the NHS of £5.7 billion).Ageing is associated with an impairment in the normally healthy muscle metabolic response to nutrition, a phenomenon that has been termed 'anabolic resistance'. Age-related muscle anabolic resistance to nutrition may underpin the progression of sarcopenia. The root-cause of age-related muscle anabolic resistance is complex, but may be partly related to periods of disuse and inactivity, which occur with increasing frequency in older individuals. Specifically, the dysregulation in muscle metabolism that occurs during successive periods of short-term disuse and inactivity may accumulate over time to form the characteristic muscle anabolic resistance of ageing. Alarmingly, muscle deterioration occurs soon after the onset of disuse in older adults. This is important as the average length of hospital stay in older individuals is 5-6 days. Therefore, we believe a focus on maintaining healthy muscle metabolism during short-term disuse events is an important research priority in the fight against sarcopenia. Resistance exercise is a potent stimulus for muscle anabolism and can offset muscle loss during disuse in older individuals. However, older individuals are typically unable (or unwilling) to perform strenuous physical activities during disuse events. Interestingly, we recently observed that resistance exercise can restore the muscle anabolic response to nutrition in older individuals, and this enhanced metabolic response persists for several days after exercise completion (after older individuals have returned to a sedentary lifestyle). Therefore, resistance exercise prior to short-term disuse (termed 'prehabilitation') may protect muscle mass, strength and metabolic function in older individuals, with important implications for the progression sarcopenia and promotion of healthy ageing. In the proposed project, we will investigate whether resistance exercise prehabilitation protects against muscle and strength loss during short-term disuse in older individuals. A cohort of healthy older individuals will complete single-leg exercise prehabilitation (for comparison with the untrained control leg), consisting of either single or multiple bouts of resistance exercise. Immediately following exercise prehabilitation, participants will undergo 5 days of strict bed-rest. Detailed assessment of muscle size, architecture, and strength will conducted prior-to and following bed-rest. Furthermore, we will use sophisticated measurement techniques to understand the precise mechanisms that underpin alterations in muscle size and strength during short-term bed rest, and whether adaptations in these mechanisms can explain the protective effects of exercise prehabilitation on muscle health. Ultimately, we hope to demonstrate that exercise prehabilitation is an effective means of preventing muscle deterioration during short-term disuse in older individuals, which will ultimately slow the trajectory of sarcopenia and promote healthy, independent ageing in a diverse and expanding older population.

骨骼肌质量在日常生活活动和代谢健康的调节中起着至关重要的作用。衰老与骨骼肌质量（肌肉减少症）的进行性下降有关，这损害了日常生活任务、代谢健康，并增加了福尔斯、骨折和死亡的风险。与治疗年龄相关的肌肉骨骼衰退相关的医疗保健成本是巨大的，并且随着我们不断扩大的老龄化人口而继续增长。值得关注的是，75-84岁的人中约有30%患有肌肉减少症。因此，减少与年龄相关的肌肉萎缩进展的干预措施将改善老年人的生活质量，并对医疗保健支出产生深远的影响。为了将其置于背景中，肌肉减少症的发病率降低10%将导致与肌肉退化相关的医疗保健支出的巨大减少（NHS的估计年度成本为57亿英镑）。衰老与正常健康的肌肉对营养的代谢反应受损有关，这种现象被称为“合成代谢抵抗”。与肌肉合成代谢有关的营养抵抗可能是肌肉减少症进展的基础。与年龄相关的肌肉合成代谢阻力的根本原因是复杂的，但可能部分与废用和不活动的时期有关，这在老年人中发生的频率越来越高。具体地说，在连续的短期废用和不活动期间发生的肌肉代谢失调可能会随着时间的推移而积累，形成衰老的特征性肌肉合成代谢抵抗。令人担忧的是，肌肉退化发生在老年人开始废用后不久。这一点很重要，因为老年人的平均住院时间为5-6天。因此，我们认为，在短期废用事件中保持健康的肌肉代谢是对抗肌肉减少症的重要研究重点。抗阻运动是一种强有力的肌肉刺激，可以抵消老年人废用期间的肌肉损失。然而，老年人通常不能（或不愿意）在废用事件期间进行剧烈的身体活动。有趣的是，我们最近观察到，阻力运动可以恢复老年人对营养的肌肉合成代谢反应，并且这种增强的代谢反应在运动完成后（老年人恢复久坐的生活方式后）持续几天。因此，在短期废用（称为“预锻炼”）之前进行抗阻运动可以保护老年人的肌肉质量、力量和代谢功能，对肌肉减少症的进展和促进健康老龄化具有重要意义。在拟议的项目中，我们将调查是否阻力运动prehistorian防止肌肉和力量损失在短期废用老年人。一组健康的老年人将完成单腿运动训练（与未经训练的对照腿进行比较），包括单次或多次抗阻运动。在运动训练后，参与者将立即进行5天的严格卧床休息。在卧床休息之前和之后，将对肌肉大小、结构和力量进行详细评估。此外，我们将使用复杂的测量技术来了解短期卧床休息期间肌肉大小和力量变化的确切机制，以及这些机制的适应是否可以解释运动预防对肌肉健康的保护作用。最终，我们希望证明运动预防是预防老年人短期废用期间肌肉退化的有效手段，这将最终减缓肌肉减少症的轨迹，并促进多样化和不断扩大的老年人口的健康，独立老龄化。

项目成果

Age-Related Anabolic Resistance of Myofibrillar Protein Synthesis Is Exacerbated in Obese Inactive Individuals.

• DOI: 10.1210/jc.2017-00869
• 发表时间: 2017-09-01
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Smeuninx B;Mckendry J;Wilson D;Martin U;Breen L
• 通讯作者: Breen L

Comparable Rates of Integrated Myofibrillar Protein Synthesis Between Endurance-Trained Master Athletes and Untrained Older Individuals.

接受过耐力训练的高水平运动员和未经训练的老年人之间的肌原纤维蛋白综合合成率相当。

• DOI: 10.3389/fphys.2019.01084
• 发表时间: 2019
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: McKendry J

The effect of short-term exercise prehabilitation on skeletal muscle protein synthesis and atrophy during bed rest in older men.

• DOI: 10.1002/jcsm.12661
• 发表时间: 2021-03
• 期刊: Journal of cachexia, sarcopenia and muscle
• 作者: Smeuninx B;Elhassan YS;Manolopoulos KN;Sapey E;Rushton AB;Edwards SJ;Morgan PT;Philp A;Brook MS;Gharahdaghi N;Smith K;Atherton PJ;Breen L
• 通讯作者: Breen L

No effect of five days of bed rest or short-term resistance exercise prehabilitation on markers of skeletal muscle mitochondrial content and dynamics in older adults.

• DOI: 10.14814/phy2.15345
• 发表时间: 2022-07
• 期刊: Physiological reports
• 影响因子: 2.5