2026/03/23 by Anne Cathrine Hyde, Pamela S Ellis, Sherif El-Khamisy +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Epigenetics and DNA Methylation #Genetics, Aging, and Longevity in Model Organisms #Zebrafish Biomedical Research Applications
paper · pdf · doi:10.1242/bio.062345
openalex publication_date 2026/03/23 · openalex created_date 2026/03/24 · openalex updated_date 2026/08/01
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 characterised 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 utilised as a model for human aging and frailty due to its high degree of genetic homology. With a short lifespan of approximately 3 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 utilising 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 standardised metric will facilitate cross-laboratory comparisons and enhance the reproducibility of future zebrafish-based ageing research.