Development of a Rat Clinical Frailty Index

Yorke, Amy; Kane, Alice E.; Friesen, Camille L. Hancock; Howlett, Susan E.; O’Blenes, Stacy B.

doi:10.1093/gerona/glw339

Cited by 47 publications

(44 citation statements)

References 44 publications

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“…Frailty assessment tools have also recently been developed for use in aging rats. For instance, the simplified mouse frailty index tool has been adapted for use in aging rats . This instrument measures the accumulation of age‐related health deficits that are specifically seen in aging rats.…”

Section: Animal Modelsmentioning

confidence: 99%

The biology of frailty in humans and animals: Understanding frailty and promoting translation

Bisset

Howlett

2019

Aging Medicine

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Frailty is a state of high vulnerability to adverse health outcomes. This concept is used to explain the heterogeneity in rates of aging in people of the same age. Frailty has important clinical implications, because even minor stressors can lead to adverse outcomes, including death, in frail individuals. Although frailty mechanisms are not well understood, advances in our ability to qualify frailty have encouraged efforts in this area. Quantification of frailty with both “frailty phenotype” and “frailty index” approaches has begun to highlight putative frailty mechanisms and new animal models of frailty are inspiring preclinical research. These models either adapt frailty phenotype and frailty index tools for use in animals or they use genetically manipulated mice that mimic conditions seen in frailty (eg, inflammation, sarcopenia, weakness). This review: describes commonly used tools to quantify frailty clinically, discusses potential frailty mechanisms, and describes animal models of frailty. It also highlights how these models have been used to explore frailty mechanisms and potential frailty interventions, including pharmacological treatments, diet, and exercise. These exciting new developments in the field have the potential to facilitate translational research, improve our understanding of mechanisms of frailty, and help develop new interventions to mitigate frailty in our aging population.

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Section: Animal Modelsmentioning

confidence: 99%

The biology of frailty in humans and animals: Understanding frailty and promoting translation

Bisset

Howlett

2019

Aging Medicine

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“…Each mouse was assessed with the MCFI at one time point and days to death post FI measurement were determined. For some analyses FI scores were stratified as either high (≥0.21) or low (<0.21), using a cut-off point that is commonly used clinically (Rockwood et al, 2011 ; Blodgett et al, 2015 ), and has been used previously in rodents (Yorke et al, 2017 ). To compare the rates of deficit accumulation in different sex and genotype groups in the present study, the natural log of the FI was plotted against age.…”

Section: Methodsmentioning

confidence: 99%

Sex Differences in Healthspan Predict Lifespan in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Kane

Shin

Wong

et al. 2018

Front. Aging Neurosci.

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Mouse models of Alzheimer’s disease (AD) exhibit marked differences in life expectancy depending on their genotype and sex. The assessment of frailty could provide a measure of healthspan to facilitate comparisons between different AD models. We used a validated mouse frailty index (FI) assessment tool to explore genotype and sex differences in lifespan and healthspan of 3xTg-AD mice and their B6129F2 wild-type (WT) controls. This tool is based on an approach commonly used in people and quantifies frailty by counting the accumulation of age-related health deficits. The number of deficits in an individual divided by the total number measured yields an FI score theoretically between 0 and 1, with higher scores denoting more frailty. Male 3xTg-AD mice aged 300–600 days had higher FI scores (Mean FI = 0.21 ± 0.03) than either male WT (Mean FI = 0.15 ± 0.01) or female 3xTg-AD mice (Mean FI = 0.10 ± 0.01), and the elevated frailty scores were accompanied by parallel increases in mortality. Frailty increased exponentially with age, and higher rates of deficit accumulation elevated mortality risk in all groups of mice. When mice were stratified by FI score, frailty predicted mortality, at least in females. Therefore, the mouse clinical FI provides a valuable tool for evaluating healthspan in mouse models of AD with different lifespans.

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“…Environmental factors such as timing and location of assessment, and housing conditions of the mice may also effect FI scores but further studies are needed. Finally, specific D r a f t items in the mouse FI can be replaced or supplemented, especially in the optimisation of the FI for other strains or species as we have recently shown in the aging rat model (Yorke et al 2017). .…”

Section: Discussionmentioning

confidence: 99%

“…It is also possible that the concept of assessing frailty as FI deficit accumulation could be applied to develop novel frailty screening tools for other species used in aging research. Our group recently modified the mouse clinical FI for use in Fischer 344 rats (Yorke et al 2017). Some of the deficits were removed, for example vision loss, as this item saturates at a young age for all albino rats, and some items were added, such as porphyrin staining which is commonly seen in ageing…”

Section: R a F Tmentioning

confidence: 99%

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Implementation of the mouse frailty index

Kane

Ayaz

Ghimire

et al. 2017

Can. J. Physiol. Pharmacol.

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Frailty is considered a state of high vulnerability for adverse health outcomes for people of the same age. Those who are frail have higher mortality, worse health outcomes, and use more health care services than those who are not frail. Despite this, little is known about the biology of frailty, the effect of frailty on pharmacological or surgical outcomes, and potential interventions to attenuate frailty. In humans, frailty can be quantified using a frailty index (FI) based on the principle of deficit accumulation. The recent development of an FI in naturally ageing mice provides an opportunity to conduct frailty research in a validated preclinical model. The mouse FI has been successfully used across a wide range of applications; however, there are some factors that should be considered in implementing this tool. This review summarises the current literature, presents some original data, and suggests areas for future research on the current applications of the mouse FI, inter-rater reliability of the FI, the effect of observer characteristics and environmental factors on mouse FI scores, and the individual items that make up the FI assessment. The implementation of this tool into preclinical frailty research should greatly accelerate translational research in this important field.

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Development of a Rat Clinical Frailty Index

Cited by 47 publications

References 44 publications

The biology of frailty in humans and animals: Understanding frailty and promoting translation

The biology of frailty in humans and animals: Understanding frailty and promoting translation

Sex Differences in Healthspan Predict Lifespan in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Implementation of the mouse frailty index

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