ABSTRACT: Deep sequencing of endogenous mRNA from Caenorhabditis elegans in the presence and absence of 1-methylnicotinamide (MNA) and nicotinic acid (NA)
Project description:Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan of different species. Contrasting recent observations, we here find that overexpression of sir-2.1, the orthologue of mammalian SirT1, does extend C. elegans lifespan. Sirtuins are known to convert NAD+ into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, also in the absence of sir-2.1. Consistently, impairment of sir-2.1 prevents extension of lifespan by nicotinic acid (NA), a NAD+ precursor. Taken together, sirtuins extend lifespan by promoting formation of MNA to generate a phase I - mediated ROS signal, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation. 9 samples: 3 mRNA profiles of C.elegans 48h after L4 exposed to nicotinic acid; 3 mRNA profiles of C.elegans 48h after L4 exposed to 1-MNA; 3 mRNA profiles of C.elegans 48h after L4 as controls (H20)
Project description:Sirtuins, a family of histone deacetylases, have a fiercely debated role in regulating lifespan of different species. Contrasting recent observations, we here find that overexpression of sir-2.1, the orthologue of mammalian SirT1, does extend C. elegans lifespan. Sirtuins are known to convert NAD+ into nicotinamide (NAM). We here find that NAM and its metabolite, 1-methylnicotinamide (MNA), extend C. elegans lifespan, also in the absence of sir-2.1. Consistently, impairment of sir-2.1 prevents extension of lifespan by nicotinic acid (NA), a NAD+ precursor. Taken together, sirtuins extend lifespan by promoting formation of MNA to generate a phase I - mediated ROS signal, providing an unexpected mechanistic role for sirtuins beyond histone deacetylation.
Project description:Deep sequencing of endogenous mRNA from Caenorhabditis elegans in the presence of 2-deoxy-D-glucose (DOG) at 4 different time points
