Abstract
Frailty is an age-related condition characterized by a multisystem functional decline, increased vulnerability to stressors, and adverse health outcomes. Quantifying the degree of frailty in humans and animals is a health measure useful for translational geroscience research. Two frailty measurements, namely the frailty phenotype (FP) and the clinical frailty index (CFI), have been validated in mice and are frequently applied in preclinical research. However, these two tools are based on different concepts and do not necessarily identify the same mice as frail. In particular, the FP is based on a dichotomous classification that suffers from high sample size requirements and misclassification problems. Based on the monthly longitudinal non-invasive assessment of frailty in a large cohort of mice, here we develop an alternative scoring method, which we called physical function score (PFS), proposed as a continuous variable that resumes into a unique function, the five criteria included in the FP. This score would not only reduce misclassification of frailty but it also makes the two tools, PFS and CFI, integrable to provide an overall measurement of health, named vitality score (VS) in aging mice. VS displays a higher association with mortality than PFS or CFI and correlates with biomarkers related to the accumulation of senescent cells and the epigenetic clock. This longitudinal non-invasive assessment strategy and the VS may help to overcome the different sensitivity in frailty identification, reduce the sample size in longitudinal experiments, and establish the effectiveness of therapeutic/preventive interventions for frailty or other age-related diseases in geriatric animals.
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Data availability
The data that support the findings of this study are available from the corresponding author (MM), upon reasonable request.
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Acknowledgements
The authors would like to acknowledge the Centro Piattaforme Tecnologiche (CPT) of Verona University for the IVIS Spectrum usage. The authors wish also to acknowledge Andrea Amoroso, Daniele Pierelli and Huillca Quispe Doctor Ambrosio from Charles River Laboratory Italia, as well as Beatrice Bartozzi and Gianni Bernardini for their precious technical support.
Funding
This work was supported by The Network IRCCS AGING “Rete Nazionale di Ricerca sull’invecchiamento e la longevità attiva – Implementazione della RoadMap nella ricerca sull’Aging (IRMA)” to FL; by Fondazione Cariplo (grant 2016–1006) “Multicomponent Analysis of Physical Frailty Biomarkers” to EN, MP, and AV; and by Ricerca Corrente funding from Italian Ministry of Health to IRCCS-INRCA (MM and MP) and to IRCCS MultiMedica (AP).
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Conceptualization: MM EN, AV. Data curation: MM, SM. Formal analysis: SM. Funding acquisition: AP, MM, AV, MP, EN, FL. Investigation: MM, GB, AS, MEG, RG. Methodology: MM, FB. Project administration: FL, MP. Supervision: AP, MP, FL. Visualization: SM. Writing—original draft: SM, MM. Writing—review and editing: MP, FP, RG, EN, AV.
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Marcozzi, S., Bigossi, G., Giuliani, M.E. et al. Comprehensive longitudinal non-invasive quantification of healthspan and frailty in a large cohort (n = 546) of geriatric C57BL/6 J mice. GeroScience 45, 2195–2211 (2023). https://doi.org/10.1007/s11357-023-00737-1
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DOI: https://doi.org/10.1007/s11357-023-00737-1