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.

Keywords: Frailty; Muscle; Sarcopenia..

Figure 1.

Criterion 1: grip strength. Left: A–K were individual grip test scores, in seconds, for each animal. The cohort mean of the grip test was 99±14 seconds. Right: the frailty criterion of the grip strength. Animals A–K were ranked from high to low (top to the bottom). The cutoff point was 31 seconds, 1.5 SD below the mean. The grip strength scores of animal H (24 seconds) and G (28 seconds) were below the 1.5 SD cutoff point (dark bars), whereas the remaining animals were above the cutoff point (light bars).

Figure 2.

Criterion 2: walking speed. Left: A–K were individual rotarod speed, in rpm, for each animal. The cohort mean of the rotarod test was 9.6±0.6rpm. Right: the frailty criterion of walking speed. Animals A–K were ranked from high to low (top to the bottom). The cutoff point was 6.8rpm, 1.5 SD below the mean. The walking speed score of animal H (6.3rpm) was below the 1.5 SD cutoff point (dark bar), whereas for the remaining animals, it is above the cutoff point (light bars).

Figure 3.

Criterion 3: physical activity. Left: A–K were individual voluntary wheel-running distances, in km/d, for each animal. The cohort mean of the voluntary wheel running was 1.53±0.25 km/d. Right: the frailty criterion of physical activity. Animals A–K were ranked from high to low (top to the bottom). The cutoff point was 0.37 km/d, 1.5 SD below the mean. The physical activity score of each mouse within our cohort was above the cutoff point (light bars).

Figure 4.

Criterion 4: endurance. Left: A–K were individual endurance scores, in seconds, for each mouse. The cohort mean of the endurance score was 74±9 seconds. Right: the frailty criterion of endurance score. Mice A–K were ranked from high to low (top to the bottom). The cutoff point was 33 seconds, 1.5 SD below the mean. The endurance scores of mouse H (23 seconds) and mouse G (31 seconds) were below the 1.5 SD cutoff point (dark bars), whereas the remaining mice were above the cutoff point (light bars).