Project description:In this work we took 9 samples from brain and 6 samples from muscle of the African turquoise killifish (Nothobranchius furzeri) at 3.5, 8.5 and 14 weeks. Total RNA was sequenced and circRNAs were detected.
Project description:The mammalian central nervous system (CNS) is susceptible to age-related pathologies, resulting in progressive, irreversible disease. Neurodegenerative eye conditions, like glaucoma and age-related macular degeneneration (AMD), are on the rise due to increased life expectancy. Despite this, there are currently no long-term therapies to prevent degeneration and vision loss. The short-lived African turquoise kililfsh (Nothobranchius furzeri GRZ-AD) is an ideal genetic model for ageing studies, exhibiting rapid ageing phenotypes within its four to six-mont lifespan. Investigating the molecular consequences of ageing in the retina, we conducted bulk RNA-sequencing, revealing dysregulation of genetic pathways associated with ageing CNS and retinal diseas in the aged killifish retina.
Project description:The mammalian central nervous system (CNS) and its retina are susceptible to age-related patholgoies, resulting in progressive, irreversible diseases like glaucoma and age-related macular degeneration (AMD), which are increasingly prevalent with rising life expectancy. Currently, there are no targeted long-term therapies to prevent vision loss. The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for ageing studies, displaying rapid ageing phenotypes within its four to six-month lifespan. Our investigation on the molecular consequences of ageing in the retina, employing scRNA-sequencing, shows a a comprehensive overview of the cellular heterogeneity of the killifish retina, uncovering age-related gene expression changes specific to certain retinal cell populations.
Project description:Here, we performed a longitudinal study of genome-wide gene expression in the short-lived killifish Nothobranchius furzeri (MZM-0410 strain) and correlated variations in transcript abundance at two time points during early adult life with age at death.
Project description:Introduction: Aging is associated with progressive loss of renal function and vascular structure, with and without chronic kidney disease. However, the mechanisms driving renal vascular aging and potential therapeutic interventions remain poorly understood. Methods: To model this state-of-affairs, we used African turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate. We then inhibited the sodium-glucose co-transporter 2 inhibition (SGLT2i) to test a potential therapeutic intervention. Histological, immunofluorescent, and 3D vascular imaging were used to evaluate glomerular, tubular, and vascular changes. Single-nuclei transcriptomic profiling was performed on whole kidneys to identify age- and treatment-associated molecular signatures. Results: Aged killifish kidneys exhibited hallmark features of human renal aging, including glomerulosclerosis, tubular fibrosis, and vascular rarefaction. Functional changes included increased proteinuria and altered tubular transporter expression. Transcriptomic profiling revealed a metabolic shift from oxidative phosphorylation to glycolysis and upregulation of pro-inflammatory pathways. Aged vasculature also displayed a marked reduction in tight junctions and cell–cell contacts. Dapagliflozin attenuated age-related vascular rarefaction, preserved functional peritubular capillary networks, and reduced albuminuria by restoring a youthful transcriptional profile and enhancing intercellular signaling. However, fish lifespan was not extended. Conclusion: This study establishes the killifish as a translational model for investigating renal vascular aging. We show that SGLT2i preserves renal microvascular structure and function, reduces proteinuria, and reprograms the aged transcriptome. These results support a vascular-protective role of SGLT2i in mitigating age-related renal deterioration.