Rodent models of frailty and their application in preclinical research

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.