Age-Dependent Response to AKI in African Turquoise Killifish

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Background: Acute kidney injury (AKI) is common, but outcomes and resolution vary markedly by age. Age-dependent regenerative capacity post-AKI is poorly understood, in part due to a lack of suitable models. We propose the short-lived African turquoise killifish (ATK, Nothobranchius furzeri) as a novel model to study renal aging and age-related AKI responses. ATK has a compressed lifespan (~4–6 months) and exhibits rapid aging, facilitating accelerated studies of age-dependent renal senescence and regeneration. Methods: AKI was induced by intraperitoneal gentamicin, following established protocols. Young (6–10 weeks) and old (>18 weeks) fish were analyzed at defined time points post-injury. Structural and molecular changes were assessed via histology (H&E, Picro Sirius Red), immunofluorescence (γ-H2AX, TUNEL), and transmission electron microscopy. Renal function was evaluated by fluorescent-dextran clearance assays, and transcriptional changes by quantitative PCR (qPCR). Results: Histology of uninjured kidneys from older fish confirmed an aged phenotype: glomerulosclerosis, tubular atrophy, and increased collagen deposition (fibrosis). Gentamicin induced AKI, as evidenced by histological damage, impaired dextran clearance, and altered gene expression. Preliminary data indicate that older fish, compared to young, exhibit an attenuated and delayed inflammatory response to AKI, accompanied by more severe functional impairment despite comparatively milder morphological injury. Conclusion: These findings demonstrate that ATK is a promising model for studying kidney aging and age-dependent AKI responses. Importantly, aged ATK kidneys develop fibrotic changes and functional decline akin to mammalian renal aging. Future studies will investigate senescence pathways to elucidate mechanisms of age-related renal regeneration. Funding: Other NIH Support - P30GM154610, Government Support – Non-U.S.

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