The biology of frailty in humans and animals: Understanding frailty and promoting translation

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.