随着年龄的增长,骨骼肌功能逐渐衰退。
Skeletal muscle dysfunction with advancing age.
机构信息
Centre of Metabolism, Ageing and Physiology (COMAP), School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, DE22 3DT, U.K.
MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research (CMAR), U.K.
出版信息
Clin Sci (Lond). 2024 Jul 17;138(14):863-882. doi: 10.1042/CS20231197.
As a result of advances in medical treatments and associated policy over the last century, life expectancy has risen substantially and continues to increase globally. However, the disconnect between lifespan and 'health span' (the length of time spent in a healthy, disease-free state) has also increased, with skeletal muscle being a substantial contributor to this. Biological ageing is accompanied by declines in both skeletal muscle mass and function, termed sarcopenia. The mechanisms underpinning sarcopenia are multifactorial and are known to include marked alterations in muscle protein turnover and adaptations to the neural input to muscle. However, to date, the relative contribution of each factor remains largely unexplored. Specifically, muscle protein synthetic responses to key anabolic stimuli are blunted with advancing age, whilst alterations to neural components, spanning from the motor cortex and motoneuron excitability to the neuromuscular junction, may explain the greater magnitude of function losses when compared with mass. The consequences of these losses can be devastating for individuals, their support networks, and healthcare services; with clear detrimental impacts on both clinical (e.g., mortality, frailty, and post-treatment complications) and societal (e.g., independence maintenance) outcomes. Whether declines in muscle quantity and quality are an inevitable component of ageing remains to be completely understood. Nevertheless, strategies to mitigate these declines are of vital importance to improve the health span of older adults. This review aims to provide an overview of the declines in skeletal muscle mass and function with advancing age, describes the wide-ranging implications of these declines, and finally suggests strategies to mitigate them, including the merits of emerging pharmaceutical agents.
由于上个世纪医学治疗和相关政策的进步,预期寿命大大提高,并且在全球范围内仍在继续增加。然而,寿命和“健康寿命”(无病健康状态下的时间长度)之间的脱节也在增加,骨骼肌肉是造成这种情况的主要原因。生物衰老伴随着骨骼肌质量和功能的下降,这被称为肌肉减少症。肌肉减少症的机制是多因素的,已知包括肌肉蛋白周转率的显著改变以及对肌肉神经输入的适应。然而,迄今为止,每个因素的相对贡献在很大程度上仍未得到探索。具体来说,随着年龄的增长,肌肉对关键合成代谢刺激的蛋白质合成反应减弱,而神经成分的改变,从运动皮层和运动神经元兴奋性到神经肌肉接头,可能解释了与质量相比功能丧失的幅度更大。这些损失的后果对个人、他们的支持网络和医疗保健服务可能是毁灭性的;对临床(例如死亡率、虚弱和治疗后并发症)和社会(例如独立性维持)结果都有明显的不利影响。肌肉数量和质量的下降是否是衰老的一个不可避免的组成部分仍有待完全理解。然而,减轻这些下降的策略对于提高老年人的健康寿命至关重要。本综述旨在概述随着年龄增长骨骼肌质量和功能的下降,描述这些下降的广泛影响,最后提出减轻这些下降的策略,包括新兴药物制剂的优点。