In recent years, nicotinamide adenine dinucleotide (NAD+) biology has been increasingly drawing significant attention within the scientific community and providing its vast implication for various age-associated pathophysiologies and disease conditions. Particularly, the role of NAD+ in the regulation of sirtuins, an evolutionary conserved family of NAD+-dependent deacetylases/deacylases, has been extensively studied. Systemic NAD+ biosynthesis mediated by intra- and extracellular nicotinamide phosphoribosyltransferase and sirtuins cooperate to regulate many fundamental biological processes in different tissues and organs and promote physiological resilience in response to nutritional and environmental perturbations. Accumulating lines of evidence suggest that systemic decline in NAD+ availability is a critical trigger for age-associated functional decline and disease conditions through the reduction in sirtuin activities in different subcellular compartments. In this chapter, we will discuss the current understanding of the intimate connection between systemic NAD+ biosynthesis and sirtuin functions and its implications in aging and longevity control.

Original languageEnglish
Title of host publicationIntroductory Review on Sirtuins in Biology, Aging, and Disease
Number of pages19
ISBN (Electronic)9780128135006
ISBN (Print)9780128134993
StatePublished - Apr 25 2018


  • Aging
  • Extracellular NAMPT (eNAMPT)
  • Hypothalamus
  • Longevity
  • NAD World
  • Nicotinamide adenine dinucleotide (NAD)
  • Nicotinamide mononucleotide (NMN)
  • Nicotinamide phosphoribosyltransferase (NAMPT)
  • Nicotinamide/nicotinic acid mononucleotide adenylyltransferases (NMNATs)
  • Sirtuins


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