The biology of frailty in humans and animals: Understanding frailty and promoting translation.
The biology of frailty in humans and animals: Understanding frailty and promoting translation.
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DOI：
10.1002/agm2.12058
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发表时间：
2019-03-01
期刊：
影响因子：
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通讯作者：
Howlett, Susan E
中科院分区：
文献类型：
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作者：
Bisset, Elise S;Howlett, Susan E
虚弱是一种极易受到不利健康后果影响的状态。这一概念被用来解释同龄人群老龄化速度的异质性。虚弱具有重要的临床意义，因为在虚弱的人中，即使是轻微的应激源也会导致不良后果，包括死亡。尽管脆弱的机制还没有被很好地理解，但我们在确定脆弱的能力方面的进步鼓励了这一领域的努力。用“脆弱表型”和“脆弱指数”方法对脆弱进行量化，已经开始强调可能的脆弱机制，新的脆弱动物模型正在激发临床前研究。这些模型要么采用动物的脆弱表型和脆弱指数工具，要么使用模仿脆弱状态(如炎症、骨骼减少、虚弱)的基因操纵的小鼠。这篇综述：描述了临床上常用的量化脆弱的工具，讨论了潜在的脆弱机制，并描述了脆弱的动物模型。它还强调了这些模型如何被用于探索脆弱机制和潜在的脆弱干预，包括药物治疗、饮食和运动。该领域的这些令人兴奋的新发展有可能促进转化研究，提高我们对脆弱机制的理解，并帮助开发新的干预措施来缓解我们老龄化人口的脆弱。
Frailty is a state of high vulnerability to adverse health outcomes. This concept is used to explain the heterogeneity in rates of aging in people of the same age. Frailty has important clinical implications, because even minor stressors can lead to adverse outcomes, including death, in frail individuals. Although frailty mechanisms are not well understood, advances in our ability to qualify frailty have encouraged efforts in this area. Quantification of frailty with both "frailty phenotype" and "frailty index" approaches has begun to highlight putative frailty mechanisms and new animal models of frailty are inspiring preclinical research. These models either adapt frailty phenotype and frailty index tools for use in animals or they use genetically manipulated mice that mimic conditions seen in frailty (eg, inflammation, sarcopenia, weakness). This review: describes commonly used tools to quantify frailty clinically, discusses potential frailty mechanisms, and describes animal models of frailty. It also highlights how these models have been used to explore frailty mechanisms and potential frailty interventions, including pharmacological treatments, diet, and exercise. These exciting new developments in the field have the potential to facilitate translational research, improve our understanding of mechanisms of frailty, and help develop new interventions to mitigate frailty in our aging population.