GSE108968 NAD+ repletion inhibits accelerated aging in Werner syndrome through the restoration of mitophagy

Contributors : Evandro F Fang ; Yujun Hou ; Martin B Jensen ; Henok Kassahun ; Marya Morevati ; Jesse S Kerr ; David Figueroa ; Beimeng Yang ; Ho-Joon Lee ; Hisaya Kato ; Tanima SenGupta ; Tyler G Demarest ; Jong-Hyuk Lee ; Domenica Caponio ; Tomasz Kulikowicz ; Aswin Mangerich ; Deborah L Croteau ; Yoshiro Maezawa ; Costas A Lyssiotis ; Mark P Mattson ; Heinrich Jasper ; Hilde Nilsen ; Vilhelm A BohrSeries Type : Expression profiling by arrayOrganism : Caenorhabditis elegansMetabolic dysfunction is a primary feature of the premature aging Werner syndrome (WS), a heritable human disease caused by mutations in the gene encoding the DNA helicase Werner (WRN). However, the relationship between WRN mutation and its severe metabolic phenotypes is unclear. Here we report mitochondrial dysfunction and depletion of NAD+, a fundamental ubiquitous cofactor, in WS patient samples and WS animal models. NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably delays accelerated aging, including stem cell dysfunction in both C. elegans and Drosophila models of WS. Mechanistically, WRN physically binds to a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) and facilitates its NAD+ production. Our findings reveal an unprecedented anti-aging mechanism of WRN that integrates its new function of NAD+ synthesis to coordinate mi...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Caenorhabditis elegans Source Type: research