Document Type
Article
Publication Date
10-1-2024
Original Citation
Luciano A,
Robinson L,
Garland G,
Lyons B,
Korstanje R,
Di Francesco A,
Churchill G.
Longitudinal fragility phenotyping contributes to the prediction of lifespan and age-associated morbidity in C57BL/6 and Diversity Outbred mice. Geroscience. 2024;46(5):4937-54.
Keywords
JMG, Animals, Longevity, Frailty, Mice, Inbred C57BL, Aging, Phenotype, Mice, Male, Machine Learning, Female, Algorithms, Longitudinal Studies, Life Expectancy, Morbidity
JAX Source
Geroscience. 2024;46(5):4937-54.
ISSN
2509-2723
PMID
38935230
DOI
https://doi.org/10.1007/s11357-024-01226-9
Grant
This work was supported by the National Institutes of Health (Nathan Shock Centers of Excellence in the Basic Biology of Aging program, grant number AG38070 to R.K. and G.C.) and Calico Life Sciences LLC (Dietary Intervention of Aging in Genetically Diverse Animals, grant number CALICO-GAC-06 to G.C.).
Abstract
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.