An Automated, Home-Cage, Video Monitoring-based Mouse Frailty Index Detects Age-associated Morbidity in C57BL/6 and Diversity Outbred Mice

Ruby, J. Graham; Francesco, Andrea Di; Ylagan, Paulo; Luo, Angela; Keyser, Robert; Williams, Owen A.; Spock, Sarah; Li, Wenzhou; Vongtharangsy, Nalien; Chatterjee, Sandip; Sloan, Cricket A.; Ledogar, Charles; Kuiper, Veronica; Kite, Janessa; Cosino, Marcelo; Cha, Paulyn; Karlsson, Eleanor M.

doi:10.1093/gerona/glad035

Cited by 6 publications

(2 citation statements)

References 52 publications

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“…Since our study was initiated, there have been significant advances in non-invasive methods for frailty assessment in mice and humans. For example, machine-vision-based FI for mice using video cameras and ML to automate frailty index scoring from morphometric features, behavioral assessment, and gait analysis [38, 39]. These methods could enable high-throughput frailty phenotyping in large colonies of aged mice without overwhelming human labor resources.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Fragility Phenotyping Predicts Lifespan and Age-Associated Morbidity in C57BL/6 and Diversity Outbred Mice

Luciano,

Robinson,

Garland

et al. 2024

Preprint

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Aging studies in mammalian models often depend on natural lifespan data as a primary outcome. Tools for lifespan prediction could accelerate these studies and reduce the need for veterinary intervention. Here, we leveraged large-scale longitudinal frailty and lifespan data on two genetically distinct mouse cohorts to evaluate noninvasive strategies to predict life expectancy in mice. We applied a modified frailty assessment, the Fragility Index, derived from existing frailty indices with additional deficits selected by veterinarians. We developed an ensemble machine learning classifier to predict imminent mortality (95% proportion of life lived [95PLL]). Our algorithm represented improvement over previous predictive criteria but fell short of the level of reliability that would be needed to make advanced prediction of lifespan and thus accelerate lifespan studies. Highly sensitive and specific frailty-based predictive endpoint criteria for aged mice remain elusive. While frailty-based prediction falls short as a surrogate for lifespan, it did demonstrate significant predictive power and as such must contain information that could be used to inform the conclusion of aging experiments. We propose a frailty-based measure of healthspan as an alternative target for aging research and demonstrate that lifespan and healthspan criteria reveal distinct aspects of aging in mice.

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Section: Discussionmentioning

confidence: 99%

Longitudinal Fragility Phenotyping Predicts Lifespan and Age-Associated Morbidity in C57BL/6 and Diversity Outbred Mice

Luciano,

Robinson,

Garland

et al. 2024

Preprint

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“…Next, we compare our prediction with published experimental data. Several experimental groups have developed the methods to directly measure frailty and sickspan in mice [35][36][37] , but to our knowledge none have yet published individual-level sickspan or longitudinal frailty index of mice cohorts under longevity interventions 37,38 . Thus we do not yet have data on sickspan in mice.…”

Section: Several Interventions In Mice Are Predicted To Compress Sick...mentioning

confidence: 99%

Compression of morbidity by interventions that steepen the survival curve

Yang,

Mayo,

Levy

et al. 2023

Preprint

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Longevity research aims to enhance the period of healthy life, known as the healthspan, while minimizing the duration of disability and morbidity, known as the sickspan. Various interventions extend lifespan in model organisms, but it is not known which of these are likely to compress the relative sickspan. Here, we present a theory that predicts which interventions effectively compress the sickspan. The theory is based on the shape of the survival curve - the fraction of organisms surviving as a function of age. Interventions that lengthen mean lifespan while preserving the shape of the survival curve, known as scaling, are hypothesized to extend the sickspan proportionally, without compressing it. Such interventions include caloric restriction and most other known longevity interventions. Conversely, a small subset of interventions that extend lifespan and alter the shape of the survival curve, particularly by steepening it, are predicted to compress the sickspan. We provide intuitive explanations for this theory and demonstrate its origin from the saturated removal model, a recent mathematical aging model calibrated in mice. We discuss specific longevity interventions in mice that steepen the survival curves, including senolytics, ketogenic diet, and agents that reduce glucose spikes and protect blood vessels, as potential candidates for compressing the sickspan. This hypothesis offers insights into the potential strategies for achieving compressed morbidity and extending healthspan.

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Preclinical Models of Frailty

Mishra,

Howlett

2024

Frailty

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An Automated, Home-Cage, Video Monitoring-based Mouse Frailty Index Detects Age-associated Morbidity in C57BL/6 and Diversity Outbred Mice

Cited by 6 publications

References 52 publications

Longitudinal Fragility Phenotyping Predicts Lifespan and Age-Associated Morbidity in C57BL/6 and Diversity Outbred Mice

Longitudinal Fragility Phenotyping Predicts Lifespan and Age-Associated Morbidity in C57BL/6 and Diversity Outbred Mice

Compression of morbidity by interventions that steepen the survival curve

Preclinical Models of Frailty

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