Frailty in rodents: Models, underlying mechanisms, and management

Frailty is a clinical geriatric syndrome characterized by decreased multisystem function and increased vulnerability to adverse outcomes. Although numerous studies have been conducted on frailty, the underlying mechanisms and management strategies remain unclear. As rodents share homology with humans, they are used extensively as animal models to study human diseases. Rodent frailty models can be classified broadly into the genetic modification and non-genetic modification models, the latter of which include frailty assessment models (based on the Fried frailty phenotype and frailty index methods) and induced frailty models. Such models were developed for use in investigating frailty-related physiological changes at the gene, cellular, molecular, and system levels, including the organ system level. Furthermore, exercise, diet, and medication interventions, in addition to their combinations, could improve frailty status in rodents. Rodent frailty models provide novel and effective tools for frailty research. In the present paper, we review research progress in rodent frailty models, mechanisms, and management, which could facilitate and guide further clinical research on frailty in older adults.