Identifying the Onset of Frailty

Abstract

PURPOSE: Frailty is a clinical syndrome associated with adverse health outcomes in older adults. Currently, there is a great need to identify interventions to prevent or delay the onset as well as decrease the burden of frailty symptoms. Identifying the onset of frailty is one of the first steps in developing effective interventions. Therefore, the purpose of this study was to determine the onset of frailty using the mouse frailty index. METHODS: Male C57BL/6J (n=32) were purchased at 12 months of age. At 14 months of age, the mice were subjected to a frailty assessment that included 5 criteria: loss of body weight, weakness (grip strength), slow walking speed (Rota-rod), low activity level (voluntary wheel running) and poor endurance (treadmill test). Mice repeated these tests every 3 months throughout their lifespan. The designated cutoff point for each frailty criterion was determined from data collected at 14 months of age and was set at 1.5 SD below the mean. If a mouse had three of the criteria scores below the cutoff points, the mouse was identified as frail, while a mouse with two criteria scores was identified as mildly frail. RESULTS: Prevalence of frailty increased across the lifespan of the mice, with 75% of the 35 month old mice identified as frail. The survival rate at 35 months of age was 25% of the original cohort. The onset of frailty occurred at 23 months of age (88% survival) while mice 17 months of age (94% survival) were considered mildly frail. Mildly frail mice fell below the cutoff points for endurance and walking speed, whereas the frail mice fell below the cutoff points for endurance, walking speed, and activity levels. Although endurance, walking speed, and activity levels were the criterion identified in the frail mice, all criteria included in the frailty assessment decreased across the lifespan of mice. Reductions were observed in body weight (5.3%), strength (18.9%) endurance (51.1%), walking speed (31.4%), and activity levels (89.9%). A progression from mildly frail to frail to mortality was observed; in that, mildly frail mice at 17 months of age were frail by 23 months and died at 26 months. CONCLUSIONS: Taken together, the onset of frailty occurs early in the lifespan and is associated with negative outcomes in mice. It provides the framework to develop interventions for preventing or delaying the frailty.