MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
NIHR Nottingham Biomedical Research Centre, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
Physiol Rev. 2023 Apr 1;103(2):1137-1191. doi: 10.1152/physrev.00037.2021. Epub 2022 Oct 14.
"Frailty" is a term used to refer to a state characterized by enhanced vulnerability to, and impaired recovery from, stressors compared with a nonfrail state, which is increasingly viewed as a loss of resilience. With increasing life expectancy and the associated rise in years spent with physical frailty, there is a need to understand the clinical and physiological features of frailty and the factors driving it. We describe the clinical definitions of age-related frailty and their limitations in allowing us to understand the pathogenesis of this prevalent condition. Given that age-related frailty manifests in the form of functional declines such as poor balance, falls, and immobility, as an alternative we view frailty from a physiological viewpoint and describe what is known of the organ-based components of frailty, including adiposity, the brain, and neuromuscular, skeletal muscle, immune, and cardiovascular systems, as individual systems and as components in multisystem dysregulation. By doing so we aim to highlight current understanding of the physiological phenotype of frailty and reveal key knowledge gaps and potential mechanistic drivers of the trajectory to frailty. We also review the studies in humans that have intervened with exercise to reduce frailty. We conclude that more longitudinal and interventional clinical studies are required in older adults. Such observational studies should interrogate the progression from a nonfrail to a frail state, assessing individual elements of frailty to produce a deep physiological phenotype of the syndrome. The findings will identify mechanistic drivers of frailty and allow targeted interventions to diminish frailty progression.
“虚弱”一词是指与非虚弱状态相比，对压力源的易感性增加和恢复能力受损的状态，它正逐渐被视为一种弹性丧失。随着预期寿命的延长和与之相关的身体虚弱时间的增加，需要了解虚弱的临床和生理特征及其驱动因素。我们描述了与年龄相关的虚弱的临床定义及其在理解这种普遍疾病发病机制方面的局限性。鉴于与年龄相关的虚弱表现为平衡不良、跌倒和活动能力下降等功能下降的形式，我们可以从生理角度来看待虚弱，并描述已知的虚弱的器官基础组成部分，包括肥胖、大脑和神经肌肉、骨骼肌肉、免疫和心血管系统，作为单独的系统以及多系统失调的组成部分。这样做的目的是强调对虚弱的生理表型的现有理解，并揭示虚弱轨迹的关键知识差距和潜在机制驱动因素。我们还回顾了人类通过运动干预来减少虚弱的研究。我们得出的结论是，老年人需要进行更多的纵向和干预性临床研究。这些观察性研究应该探究从不虚弱状态到虚弱状态的进展，评估虚弱的各个要素，以产生该综合征的深层生理表型。研究结果将确定虚弱的机制驱动因素，并允许进行有针对性的干预来减缓虚弱的进展。
