Two hallmarks of aging in GRZ and MZCS strains of nothobranchius furzeri : Mitochondrial dysfunction and loss of proteostasis

Details

Supervisors

Page, Melissa ; Rees, Jean-François

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries, à finalité spécialisée

Abstract

enThe global demographic landscape is changing, with a growing proportion of older individuals and, as a result, an increase in age-related diseases such as Alzheimer’s and Parkinson’s. Clarifying how aging and neurodegenerative diseases develop at cellular and molecular levels is therefore essential. This thesis investigated two hallmarks of aging in vivo: mitochondrial dysfunction and loss of proteostasis. The turquoise killifish Nothobranchius furzeri was chosen as a model, primarly, because of its naturally short lifespan, which makes it particularly suitable for aging studies. Two strains were included: GRZ, a highly inbred line with reduced longevity, and MZCS, a more diverse population with a longer lifespan. The study was structured in two parts. First, mitochondrial DNA (mtDNA) copy number per cell was measured in brain and liver at different ages in both strains, in order to compare how mtDNA changes with age and genetic background. In a second step, Fluorescence confocal microscopy was used in the MZCS strain to examine mitochondrial abundance through ATP synthase staining, and to explore loss of proteostasis by detecting aggresome-like structures in the brain. By combining quantitative and imaging approaches, this work aimed to provide a better picture of how mitochondria and proteostasis are changing with aging in N. furzeri. It also highlights the interest of comparing strains with distinct genetic backgrounds as a way to study the cellular mechanisms of aging and neurodegeneration without relying on transgenic organisms.