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NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity
Journal article   Open access   Peer reviewed

NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity

Charles Evans, Katrina Bogan, Peng Song, Charles Burant, Robert Kennedy and Charles Brenner
BMC Chemical Biology, Vol.10(1), pp.2-2
02/22/2010
DOI: 10.1186/1472-6769-10-2
PMCID: PMC2834649
PMID: 20175898
url
https://doi.org/10.1186/1472-6769-10-2View
Published (Version of record) Open Access

Abstract

BACKGROUND: NAD+ is a coenzyme for hydride transfer enzymes and a substrate for sirtuins and other NAD+-dependent ADPribose transfer enzymes. In wild-type Saccharomyces cerevisiae, calorie restriction accomplished by glucose limitation extends replicative lifespan in a manner that depends on Sir2 and the NAD+ salvage enzymes, nicotinic acid phosphoribosyl transferase and nicotinamidase. Though alterations in the NAD+ to nicotinamide ratio and the NAD+ to NADH ratio are anticipated by models to account for the effects of calorie restriction, the nature of a putative change in NAD+ metabolism requires analytical definition and quantification of the key metabolites. RESULTS: Hydrophilic interaction chromatography followed by tandem electrospray mass spectrometry were used to identify the 12 compounds that constitute the core NAD+ metabolome and 6 related nucleosides and nucleotides. Whereas yeast extract and nicotinic acid increase net NAD+ synthesis in a manner that can account for extended lifespan, glucose restriction does not alter NAD+ or nicotinamide levels in ways that would increase Sir2 activity. CONCLUSIONS: The results constrain the possible mechanisms by which calorie restriction may regulate Sir2 and suggest that provision of vitamins and calorie restriction extend lifespan by different mechanisms.

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