Toward productive aging: SIRT1, systemic NAD biosynthesis, and the NAD world.

In our current society, achieving "productive aging," which aims to keep people as productive as possible with good health and spirit for their private and social activities as they grow older, will be important to maximize the duration of high quality of life and to promote a stable economy and solvent social security in healthcare systems. To achieve this goal, we have been studying mechanisms of mammalian aging and longevity, focusing on the physiological importance of the mammalian nicotinamide adenine dinucleotide (NAD)--dependent protein deacetylase SIRT1 and systemic NAD biosynthesis mediated by nicotinamide phosphoribosyltransferase for the regulation of metabolism and aging. Through these studies, we have recently proposed a comprehensive concept of a novel systemic regulatory network for metabolism and aging, named "NAD World." This new concept of NAD World also conveys ideas of functional hierarchy and frailty for the induction of aging in mammals. Details of the NAD World and its implications to age-associated metabolic diseases such as type 2 diabetes will be discussed.