Assessing frailty in aged zebrafish using a quick pseudo-frailty index

While biomedical advancements have significantly extended human longevity, increased lifespan is frequently decoupled from healthspan, as these additional years are often accompanied by frailty and chronic morbidity. Frailty is characterized by a multisystem decline in physiological reserve, and renders individuals disproportionately vulnerable to adverse outcomes -including mortality- when faced with health stressors. Consequently, research into the biological mechanisms linking ageing to the onset of frailty is needed. The zebrafish is increasingly utilized as a model for human aging and frailty due to its high degree of genetic homology. With a short lifespan of approximately three years, zebrafish show several conserved senescent phenotypes, including cataracts, sarcopenia, spinal curvature, and motor decline. Crucially, as in humans, ageing in zebrafish is not strictly chronological; apparent biological age often diverges from calendar age, with physical condition indicating frailty status more accurately. We propose a frailty index designed to evaluate the divergence between successful ageing and frailty in zebrafish. By utilizing easily quantifiable phenotypic markers such as spinal curvature and Body Mass Index, this index provides a score that predicts frailty status as validated against expert assessment. Implementing this standardized metric will facilitate cross-laboratory comparisons and enhance the reproducibility of future zebrafish-based ageing research.