The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans.
The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans.
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DOI：
10.1016/j.arr.2018.07.005
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发表时间：
2018-11
影响因子：
13.1
通讯作者：
Atherton PJ
中科院分区：
文献类型：
--
作者：
Wilkinson DJ;Piasecki M;Atherton PJ
随着年龄的增长，肌肉量的减少是由于单个肌肉纤维的萎缩和丧失。合成代谢抵抗是与年龄相关的纤维萎缩的基础。纤维的丧失与运动单元的去神经支配和重塑有关。在今后的研究中应考虑这两个因素的可塑性。与年龄相关的骨骼肌质量和功能丧失，即肌肉减少症，除了与全因死亡率有关外，还与身体虚弱和发病率（慢性病）风险增加有关。肌肉量的减少最初发生在中年（每年约1%），在严重的情况下，到8 - 9岁时可导致肌肉量减少约50%。这篇综述将重点关注随着年龄增长的肌肉退化，并强调调节肌肉质量和功能下降的两种基本机制：肌纤维萎缩和肌纤维损失（发育不全）及其测量。人类肌纤维萎缩的机制与肌肉蛋白合成（MPS）和分解（MPB）的不平衡有关；然而，由于肌肉蛋白质转换的基础改变证据有限，因此，对调节肌肉昼夜动态平衡的基本环境信号（即体力活动和营养）的“合成代谢抵抗”似乎是肌肉蛋白质平衡中与年龄相关的分解代谢扰动的基础。虽然衰老肌肉对合成代谢刺激脱敏的“上游”驱动因素尚未明确，但它们最有可能与营养/运动刺激转化为影响mRNA翻译和蛋白质水解的信号的效率受损有关。此外，在解剖纤维计数的尸体研究中显示了肌肉纤维的损失，从iEMG研究中显示了运动单元的损失，尽管在人类中很少有分子研究。我们认为，确定对抗肌肉减少症的对策需要更好地理解肌肉纤维萎缩和纤维损失的协调调节，这可能是不可分割的联系。
Loss of muscle mass with age is due to atrophy and loss of individual muscle fibres. Anabolic resistance is fundamental in age-related fibre atrophy. Fibre loss is associated with denervation and remodelling of motor units. The plasticity of both factors should be considered in future research. Age-related loss of skeletal muscle mass and function, sarcopenia, is associated with physical frailty and increased risk of morbidity (chronic diseases), in addition to all-cause mortality. The loss of muscle mass occurs incipiently from middle-age (∼1%/year), and in severe instances can lead to a loss of ∼50% by the 8–9th decade of life. This review will focus on muscle deterioration with ageing and highlight the two underpinning mechanisms regulating declines in muscle mass and function: muscle fibre atrophy and muscle fibre loss (hypoplasia) – and their measurement. The mechanisms of muscle fibre atrophy in humans relate to imbalances in muscle protein synthesis (MPS) and breakdown (MPB); however, since there is limited evidence for basal alterations in muscle protein turnover, it would appear that “anabolic resistance” to fundamental environmental cues regulating diurnal muscle homeostasis (namely physical activity and nutrition), underlie age-related catabolic perturbations in muscle proteostasis. While the ‘upstream’ drivers of the desensitization of aged muscle to anabolic stimuli are poorly defined, they most likely relate to impaired efficiency of the conversion of nutritional/exercise stimuli into signalling impacting mRNA translation and proteolysis. Additionally, loss of muscle fibres has been shown in cadaveric studies using anatomical fibre counts, and from iEMG studies demonstrating motor unit loss, albeit with few molecular investigations of this in humans. We suggest that defining countermeasures against sarcopenia requires improved understandings of the co-ordinated regulation of muscle fibre atrophy and fibre loss, which are likely to be inextricably linked.
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DOI：
10.1113/jp272857
发表时间：
2016-12-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Brook MS;Wilkinson DJ;Mitchell WK;Lund JN;Phillips BE;Szewczyk NJ;Greenhaff PL;Smith K;Atherton PJ
通讯作者：
Atherton PJ
DOI：
10.1111/apha.12532
发表时间：
2016-01
期刊：
Acta physiologica (Oxford, England)
影响因子：
--
作者：
Brook MS;Wilkinson DJ;Phillips BE;Perez-Schindler J;Philp A;Smith K;Atherton PJ
通讯作者：
Atherton PJ
影响因子：
7.1
作者：
Atherton, Philip J.;Etheridge, Timothy;Rennie, Michael J.
通讯作者：
Rennie, Michael J.
影响因子：
6
作者：
BENNET, WM;CONNACHER, AA;RENNIE, MJ
通讯作者：
RENNIE, MJ
DOI：
10.1152/ajpendo.00415.2005
发表时间：
2006-04-01
影响因子：
5.1
作者：
Cuthbertson, DJ;Babraj, J;Rennie, M
通讯作者：
Rennie, M