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Title of Journal: Cell Biochem Biophys

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Abbravation: Cell Biochemistry and Biophysics

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Humana Press Inc

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DOI

10.1007/s10354-005-0238-5

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1559-0283

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The NAD World A New Systemic Regulatory Network f

Authors: Shinichiro Imai
Publish Date: 2009/01/07
Volume: 53, Issue: 2, Pages: 65-
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Abstract

For the past several years it has been demonstrated that the NADdependent protein deacetylase Sirt1 and nicotinamide phosphoribosyltransferase Namptmediated systemic NAD biosynthesis together play a critical role in the regulation of metabolism and possibly aging in mammals Based on our recent studies on these two critical components we have developed a hypothesis of a novel systemic regulatory network named “NAD World” for mammalian aging Conceptually in the NAD World systemic NAD biosynthesis mediated by intra and extracellular Nampt functions as a driver that keeps up the pace of metabolism in multiple tissues/organs and the NADdependent deacetylase Sirt1 serves as a universal mediator that executes metabolic effects in a tissuedependent manner in response to changes in systemic NAD biosynthesis This new concept of the NAD World provides important insights into a systemic regulatory mechanism that fundamentally connects metabolism and aging and also conveys the ideas of functional hierarchy and frailty for the regulation of metabolic robustness and aging in mammalsI thank all members of the Imai lab for their helpful discussions and comments I apologize to those whose work is not cited due to the focus of this review and space limitations This work was supported by grants from the National Institute on Aging AG024150 Ellison Medical Foundation and Longer Life Foundation to S I

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