Calorie restriction extends yeast life span by lowering the level of NADH
TL;DR: It is shown that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2, validating the model that NADh regulates yeast longevity in response to CR.
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Abstract: Calorie restriction (CR) extends life span in a wide variety of species. Previously, we showed that calorie restriction increases the replicative life span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase. Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR.
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Regulatory Effects of NAD+ Metabolic Pathways on Sirtuin Activity
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TL;DR: Current results and thinking of how NAD+ metabolic pathways regulate sirtuin activities and how regulated NAD+ levels can impact cell physiology are described and Nicotinamide riboside and nicotinamide mononucleotide precursors are discussed.
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A fluorescent turn-on probe for nitroreductase imaging in living cells and tissues under hypoxia conditions
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References
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.
3.6K
Guide to yeast genetics and molecular biology
Christine Guthrie,Gerald R. Fink +1 more
TL;DR: This volume and its companion, Volume 350, are specifically designed to meet the needs of graduate students and postdoctoral students as well as researchers, by providing all the up-to-date methods necessary to study genes in yeast.
2.6K
The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
TL;DR: It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
TL;DR: In this paper, the lifespan of C. elegans strains containing duplications of chromosomal regions was surveyed and it was shown that a duplication containing sir-2.1-the SIR2 gene most homologous to yeast-confers a lifespan that is extended by up to 50%.
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Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae
TL;DR: These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.
1.9K