期刊
CELL BIOCHEMISTRY AND BIOPHYSICS
卷 53, 期 2, 页码 65-74出版社
HUMANA PRESS INC
DOI: 10.1007/s12013-008-9041-4
关键词
NAD World; Metabolism; Aging; Sirt1; Nampt; Systemic NAD biosynthesis; Pancreatic beta cells; Neurons; Robustness; Frailty
资金
- National Institute on Aging [AG024150]
- Ellison Medical Foundation,
- Longer Life Foundation
- NATIONAL INSTITUTE ON AGING [R01AG024150] Funding Source: NIH RePORTER
For the past several years, it has been demonstrated that the NAD-dependent protein deacetylase Sirt1 and nicotinamide phosphoribosyltransferase (Nampt)-mediated 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 NAD-dependent deacetylase Sirt1 serves as a universal mediator that executes metabolic effects in a tissue-dependent 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 mammals.
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