Cholesterol is crucial to maintain normal cellular function. In human, it has also been involved in various neurodegeneration processes, as Niemann-Pick and Alzheimer diseases. Recently, we have identified a small nucleolar RNA (jouvence) required in the epithelial cells of the gut (enterocytes), and showed that its overexpression extends lifespan. A transcriptomic analysis has revealed a deregulation of several genes in jouvence mutants. Among them, ninaD encoding a mammalian homolog to class B Scavenger receptor is importantly upregulated. In Drosophila, ninaD is required for the uptake of the dietary carotenoid, used for the formation of rhodopsin. Here, we show that jouvence-deleted flies are deficient in cholesterol-ester, as well as old flies present neurodegenerative lesions. Restoring ninaD mRNA expression level in enterocytes restores the metabolic cholesterol-ester level, prevents neurodegeneration and extends lifespan, revealing a gut-brain axis. Our studies demonstrates that ninaD is a central regulator of cholesterol homeostasis and a longevity-promoting factor.
bioRxiv Subject Collection: Neuroscience