SPELL - Nematode

Citation	Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H, Shamanna RA, Kalyanasundaram S, Bollineni RC, Wilson MA, Iser WB, Wollman BN, Morevati M, Li J, Kerr JS, Lu Q, Waltz TB, Tian J, Sinclair DA, Mattson MP, Nilsen H, Bohr VA. NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metab, 2016.
PubMed ID	27732836
Short Description	NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. GEO Record: N.A. Platform: N.A. Download gene-centric, log2 transformed data: WBPaper00051555.ce.mr.csv
# of Conditions	48
Full Description	Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD(+), and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD(+) reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan inboth animal models. Mechanistically, treatments that increase intracellular NAD(+) also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions. Experimental Details: WBPaper00051555:N2_Control_Day1_Rep1 WBPaper00051555:N2_Control_Day1_Rep2 WBPaper00051555:N2_Control_Day1_Rep3 WBPaper00051555:N2_Nicotinamide-Riboside_Day1_Rep1 WBPaper00051555:N2_Nicotinamide-Riboside_Day1_Rep2 WBPaper00051555:N2_Nicotinamide-Riboside_Day1_Rep3 WBPaper00051555:N2_Sirtuin1720_Day1_Rep1 WBPaper00051555:N2_Sirtuin1720_Day1_Rep2 WBPaper00051555:N2_Sirtuin1720_Day1_Rep3 WBPaper00051555:N2_Olaparib_Day1_Rep1 WBPaper00051555:N2_Olaparib_Day1_Rep2 WBPaper00051555:N2_Olaparib_Day1_Rep3 WBPaper00051555:atm-1(gk186)_Control_Day1_Rep1 WBPaper00051555:atm-1(gk186)_Control_Day1_Rep2 WBPaper00051555:atm-1(gk186)_Control_Day1_Rep3 WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day1_Rep1 WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day1_Rep2 WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day1_Rep3 WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day1_Rep1 WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day1_Rep2 WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day1_Rep3 WBPaper00051555:atm-1(gk186)_Olaparib_Day1_Rep1 WBPaper00051555:atm-1(gk186)_Olaparib_Day1_Rep2 WBPaper00051555:atm-1(gk186)_Olaparib_Day1_Rep3 WBPaper00051555:N2_Control_Day10_Rep1 WBPaper00051555:N2_Control_Day10_Rep2 WBPaper00051555:N2_Control_Day10_Rep3 WBPaper00051555:N2_Nicotinamide-Riboside_Day10_Rep1 WBPaper00051555:N2_Nicotinamide-Riboside_Day10_Rep2 WBPaper00051555:N2_Nicotinamide-Riboside_Day10_Rep3 WBPaper00051555:N2_Sirtuin1720_Day10_Rep1 WBPaper00051555:N2_Sirtuin1720_Day10_Rep2 WBPaper00051555:N2_Sirtuin1720_Day10_Rep3 WBPaper00051555:N2_Olaparib_Day10_Rep1 WBPaper00051555:N2_Olaparib_Day10_Rep2 WBPaper00051555:N2_Olaparib_Day10_Rep3 WBPaper00051555:atm-1(gk186)_Control_Day10_Rep1 WBPaper00051555:atm-1(gk186)_Control_Day10_Rep2 WBPaper00051555:atm-1(gk186)_Control_Day10_Rep3 WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day10_Rep1 WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day10_Rep2 WBPaper00051555:atm-1(gk186)_Nicotinamide-Riboside_Day10_Rep3 WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day10_Rep1 WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day10_Rep2 WBPaper00051555:atm-1(gk186)_Sirtuin1720_Day10_Rep3 WBPaper00051555:atm-1(gk186)_Olaparib_Day10_Rep1 WBPaper00051555:atm-1(gk186)_Olaparib_Day10_Rep2 WBPaper00051555:atm-1(gk186)_Olaparib_Day10_Rep3.
Tags	Method: microarray, Species: Caenorhabditis elegans, Topic: response to chemical