A possibility of nutriceuticals as an anti-aging intervention: activation of sirtuins by promoting mammalian NAD biosynthesis.
Aging science has recently drawn much attention, and discussions on the possibility of anti-aging medicine have multiplied. One potential target for the development of anti-aging drugs is the SIR2 (silent information regulator 2) family of NAD-dependent deacetylases/ADP-ribosyltransferases, called "sirtuins." Sirtuins regulate many fundamental biological processes in response to a variety of environmental and nutritional stimuli. In mammals, the mammalian SIR2 ortholog SIRT1 has been most studied, and small molecule SIRT1 activators (STACs), including a plant-derived polyphenolic compound resveratrol, have been developed. On the other hand, sirtuin activity is regulated by NAD biosynthetic pathways, and nicotinamide phosphoribosyltransferase (NAMPT) plays a critical role in the regulation of mammalian sirtuin activity. Recent studies have provided a proof of concept for the idea that nicotinamide mononucleotide (NMN), the NAMPT reaction product, can be used as a nutriceutical to activate SIRT1 activity. Based on these recent findings, the possibility of sirtuin-targeted nutriceutical development will be discussed.
Imai
Shin-Ichiro
S
Department of Developmental Biology, Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, USA. imaishin@wustl.edu
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015195:Drug Design; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D009243:NAD / Q000096:biosynthesis*; D009537:Nicotinamide Mononucleotide / Q000494:pharmacology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000502:physiology; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D037761:Sirtuins / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000494:pharmacology*
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D054852:Small Molecule Libraries; D009243:NAD; D009537:Nicotinamide Mononucleotide; D054409:Nicotinamide Phosphoribosyltransferase; D037761:Sirtuins