SPELL - Nematode

Citation	Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Morevati M, Lee HJ, Kato H, Kassahun H, Lee JH, Filippelli D, Okur MN, Mangerich A, Croteau DL, Maezawa Y, Lyssiotis CA, Tao J, Yokote K, Rusten TE, Mattson MP, Jasper H, Nilsen H, Bohr VA. NAD⁺ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun, 2019.
PubMed ID	31754102
Short Description	NAD⁺ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. GEO Record: GSE108968 Platform: GPL10094 Download gene-centric, log2 transformed data: WBPaper00058882.ce.mr.csv
# of Conditions	32
Full Description	Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD⁺, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD⁺ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). 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 extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD⁺ levels counteracts WS phenotypes. Experimental Details: WBPaper00058882:N2_control_rep1 WBPaper00058882:N2_control_rep2 WBPaper00058882:N2_control_rep3 WBPaper00058882:N2_control_rep4 WBPaper00058882:N2_NR_rep1 WBPaper00058882:N2_NR_rep2 WBPaper00058882:N2_NR_rep3 WBPaper00058882:N2_NR_rep4 WBPaper00058882:N2_SRIT1_rep1 WBPaper00058882:N2_SRIT1_rep2 WBPaper00058882:N2_SRIT1_rep3 WBPaper00058882:N2_SRIT1_rep4 WBPaper00058882:N2_Ola_rep1 WBPaper00058882:N2_Ola_rep2 WBPaper00058882:N2_Ola_rep3 WBPaper00058882:N2_Ola_rep4 WBPaper00058882:wrn-1(gk99)_control_rep1 WBPaper00058882:wrn-1(gk99)_control_rep2 WBPaper00058882:wrn-1(gk99)_control_rep3 WBPaper00058882:wrn-1(gk99)_control_rep4 WBPaper00058882:wrn-1(gk99)_NR_rep1 WBPaper00058882:wrn-1(gk99)_NR_rep2 WBPaper00058882:wrn-1(gk99)_NR_rep3 WBPaper00058882:wrn-1(gk99)_NR_rep4 WBPaper00058882:wrn-1(gk99)_SRIT1_rep1 WBPaper00058882:wrn-1(gk99)_SRIT1_rep2 WBPaper00058882:wrn-1(gk99)_SRIT1_rep3 WBPaper00058882:wrn-1(gk99)_SRIT1_rep4 WBPaper00058882:wrn-1(gk99)_Ola_rep1 WBPaper00058882:wrn-1(gk99)_Ola_rep2 WBPaper00058882:wrn-1(gk99)_Ola_rep3 WBPaper00058882:wrn-1(gk99)_Ola_rep4.
Tags	Method: microarray, Species: Caenorhabditis elegans, Topic: WT vs. mutant