Clinically Relevant Frailty Index for Mice

Abstract

Frailty is a clinical syndrome associated with the aging process and adverse outcomes. The purpose of this short report was to initiate the development of a Frailty Index in 27- to 28-month-old C57BL/6 mice that matched the clinical criteria used in humans (weakness, slow walking speed, low activity level, poor endurance). The selected criteria included grip strength, walking speed, physical activity, and endurance. The criteria in mice were evaluated by the inverted-cling grip test, rotarod test, voluntary wheel running, and derived endurance scores. Each criterion had a designated cutoff point (1.5 SD below the cohort mean) to identify the mice with the lowest performance. If a mouse presented with three of the criteria scores below the cutoff points, it was identified as frail. Mild frailty was designated if two criteria were below the cutoff points. In this mouse cohort, one mouse was identified as frail and one was mildly frail. This prevalence of 9% frailty is consistent with the prevalence of frailty in humans at the same survival age. Collectively, our selected criterion, cutoff point, and Frailty Index provide a potential standardized definition for frailty in mice that is consistent with the operational definition of frailty in humans.

Animal models of frailty: current applications in clinical research

“…Based upon this work, Liu et al35 developed a mouse frailty assessment tool based on the human phenotype model of frailty. This assessment tool assesses a mouse as frail based on its grip strength (assessed with the inverted-cling grip test), maximal walking speed (assessed by rotarod), physical activity (assessed by voluntary wheel running), and endurance (composite score of rotarod and grip strength performance).…”

“…Furthermore, the criteria do not completely mimic the human phenotype assessment as there is no weight loss factor, and the endurance factor is calculated from 2 of the other measured outcomes. The authors do identify that other criterion could be used in this assessment, such as treadmill running to exhaustion as an endurance measure 35. The addition of a weight loss factor, and a non-derived endurance measure may improve the translatability of this preclinical model.…”

Translational Geroscience: Emphasizing function to achieve optimal longevity

“…Several of these approaches allow the same functions to be studied in preclinical models and humans, with the potential to extend observations to population aging [27, 39-42]. Recent development of animal models for assessing declines in integrative assessments of motor and cognitive function with primary aging, as well as syndromes of aging such as frailty, provide previously unavailable experimental opportunities for determining the efficacy of therapies on functional outcomes [40, 41, 43-46]. Such models open possibilities for more direct translation of interventions from model organisms and rodents to populations of middle-aged/older adult humans using new instruments like the NIH Toolbox test batteries for assessment of motor, cognitive and sensory function [47].…”

“…To facilitate comparisons among studies, measurements should be reliable, highly standardized and, to help ensure translational relevance, validated against human populations whenever possible [40, 41, 43]. To provide the greatest possible access for investigators, assessments of function also should be cost-effective and non-proprietary, as in the case of the recently launched NIH Toolbox testing batteries in human subjects [47].…”

Comparison Between Korean Version of Physical Activity Scale for the Elderly and International Physical Activity Questionnaire-Short Form in Evaluation of Frailty Phenotype

“…In general, most tools can be categorized as either a phenotype model or an accumulationof-deficit model 2,3,6) . Many clinical and preclinical studies used the Cardiovascular Health Study (CHS) frailty phenotype as a reference standard method [7][8][9][10] . As the construct validity and predictive validity of the CHS frailty phenotype have also been demonstrated in older Koreans 5) , the CHS frailty phenotype is widely used for varying purposes in Korea 8,11) .…”