Preclinical models of frailty: Focus on interventions and their translational impact: A review

Abstract

The concept of frailty refers to heterogeneity in the risk of adverse outcomes for people of the same age. It is traditionally thought of as the inability of the body to maintain homeostasis. It can help explain differences between chronological and biological age and can quantify healthspan in experimental studies. Although clinical studies have developed tools to quantify frailty over the past two decades, preclinical models of frailty have only recently been introduced. This review describes the notion of frailty and outlines two commonly used clinical approaches to quantify frailty: The frailty phenotype and the frailty index. Translation of these methodologies for use in animals is introduced and studies that use these models to evaluate interventions designed to attenuate or exacerbate frailty are discussed. These include studies involving manipulation of diet, implementation of exercise regimens and tests of pharmaceutical agents to exacerbate or attenuate frailty. Together, this body of work suggests that preclinical frailty assessment tools are a valuable new resource to quantify the impact of interventions on overall health. Future studies could deploy these models to evaluate new frailty therapies, test combinations of interventions and assess interventions to enhance the ability to resist stressors in the setting of ageing.