Evaluating frailty assessment tools and biological frailty markers in C57BL/6 female mice

Frailty is a complex condition characterized by a decline in multiple physiological systems, compromising an individual's ability to maintain homeostasis. The onset and progression of frailty are linked to negative health outcomes such as disability, hospitalization, and mortality. To better understand frailty mechanisms, animal models have become valuable due to their accessibility to critical tissues and the ability to control variables. This study investigates frailty in female C57BL/6JN mice by comparing the two most widely accepted frailty assessment tools-the Physical Phenotype (PP) and the Frailty Index (FI). While FI relies on the accumulation of health deficits, PP focuses on functional physical performance. Our results suggest that these tools are complementary rather than interchangeable, each targeting distinct markers of frailty. To address the limitations of both, we propose a new combined assessment tool, the Vitality Phenotype (VP), which integrates physical performance and health deficits into a more comprehensive evaluation. We also explore the challenges in standardizing frailty cutoff values and the need for a reference group to enhance the accuracy of frailty identification. Lastly, we investigate the correlation between frailty criteria and biological markers, particularly bone mineral density (BMD), which shows a significant relationship with physical performance metrics such as grip strength and voluntary wheel activity, highlighting its potential role in frailty pathophysiology.