Assessing onset, prevalence and survival in mice using a frailty phenotype

Abstract

Little is known whether frailty assessments in mice are capable of distinguishing important characteristics of the frailty syndrome. The goals of this study were to identify the onset and the prevalence of frailty across the lifespan and to determine if a frailty phenotype predicts mortality. Body weight, walking speed, strength, endurance and physical activity were assessed in male C57BL/6 mice every three months starting at 14 months of age. Mice that fell in the bottom 20% for walking speed, strength, endurance and physical activity, and in the top 20% for body weight were considered to have a positive frailty marker. The onset of frailty occurred at 17 months, and represented only 3.5% of the mouse cohort. The percentage of frail mice increased with age until basically every mouse was identified as frail. Frail, pre-frail, and non-frail mice had mean survival ages of 27, 29 and 34 months, respectively. In closing, frail mice lack resilience; in that, multiple tissue/organ systems may deteriorate at an accelerated rate and ultimately lead to early mortality when compared to non-frail mice. Identifying the onset and prevalence of frailty, in addition to predicting mortality, has potential to yield information about several aging processes.

Short-Term ONX-0914 Administration: Performance and Muscle Phenotype in Mdx Mice

“…On Day 1 and 8, the mice were placed on the Rota-Rod (PanLabLetica, Cornella, Spain) and walked at 4 rpm for 30 s [ 39 , 40 ]. Next, the rotation speed increased to 40 rpm over a 5-min period.…”

“…The mice were placed on the grip meter grid (Coulbourn Instruments, Whitehall, PA, USA) and the tail was pulled back (torso kept in horizontal position) [ 39 , 40 ]. When the mouse was unable to maintain its grip, the trial ended, and the maximal grip strength was recorded (in grams).…”

Identifying Characteristics of Frailty in Female Mice Using a Phenotype Assessment Tool

“…The updated frailty index includes clinical observations of several biological systems (ie, musculoskeletal, integument, ocular, nasal systems, and respiratory) and signs of discomfort, body weight, and temperature. On the other hand, the original mouse frailty phenotype ( 8 ) was recently modified with the inclusion of body weight and an established endurance test (ie, time to fatigue on a motorized treadmill) ( 12 ). Using this updated frailty phenotype, Baumann and colleagues ( 12 ) identified the onset and prevalence of frailty, and overall health and mortality risk in a cohort of male mice across the life span (14–37 months of age).…”

“…On the other hand, the original mouse frailty phenotype ( 8 ) was recently modified with the inclusion of body weight and an established endurance test (ie, time to fatigue on a motorized treadmill) ( 12 ). Using this updated frailty phenotype, Baumann and colleagues ( 12 ) identified the onset and prevalence of frailty, and overall health and mortality risk in a cohort of male mice across the life span (14–37 months of age). The onset of frailty occurred at 17 months of age (100% survival rate) with the prevalence of frailty increasing across the life span; in that, nearly every mouse was frail by 32 months of age (52% survival rate).…”

“…The onset of frailty occurred at 17 months of age (100% survival rate) with the prevalence of frailty increasing across the life span; in that, nearly every mouse was frail by 32 months of age (52% survival rate). Because high body weight has potential to impact health status ( 12 , 15 ), the authors recommend heavy mice late in adulthood be considered positive for the frailty criterion of body weight.…”