Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada; Department of Medicine (Geriatric Medicine), Dalhousie University, Halifax, NS, Canada.
Mech Ageing Dev. 2019 Apr;179:1-10. doi: 10.1016/j.mad.2019.01.008. Epub 2019 Jan 28.
In clinical medicine, the concept of frailty is viewed as a state of high vulnerability to adverse health outcomes in people of the same age. Frailty is an important challenge because the loss of physiological reserve means that even minor stressors can lead to disability and death in those who are frail. Even so, the biology of frailty is not well understood. Rodent models of frailty are stimulating research into the biology of frailty. These pre-clinical models are based on "reverse-translation". Investigators have adapted either the "frailty phenotype" approach or the "frailty index" approach, originally developed in humans, for use in animals. This review briefly describes rodent models of frailty, discusses how these models have been used to explore mechanisms of frailty and how they have been employed to assess the impact of frailty on various experimental outcomes. The review also highlights studies that have used rodent models to investigate interventions to attenuate frailty, including drug treatment, dietary modifications and exercise. The ability to model frailty in animals is an exciting development that promises to accelerate the translation of laboratory discoveries into new clinical interventions, and situates frailty research in the larger context of geroscience.
在临床医学中，衰弱被视为同年龄段人群易发生不良健康后果的一种高度脆弱状态。衰弱是一个重要的挑战，因为生理储备的丧失意味着，即使是轻微的压力源也会导致脆弱人群残疾和死亡。即便如此，衰弱的生物学机制仍未得到很好的理解。衰弱的啮齿动物模型正在激发对衰弱生物学的研究。这些临床前模型是基于“反向翻译”。研究人员已经调整了最初在人类中开发的“衰弱表型”方法或“衰弱指数”方法，以便在动物中使用。这篇综述简要描述了衰弱的啮齿动物模型，讨论了这些模型如何用于探索衰弱的机制，以及如何用于评估衰弱对各种实验结果的影响。该综述还强调了使用啮齿动物模型研究减弱衰弱的干预措施的研究，包括药物治疗、饮食改变和运动。在动物中建模衰弱的能力是一个令人兴奋的发展，有望加速实验室发现转化为新的临床干预措施，并将衰弱研究置于老年科学的更大背景下。
