NAD+ Deficiency Is a Common Central Pathological Factor of a Number of Diseases and Aging: Mechanisms and Therapeutic Implications

Antioxid Redox Signal. 2019 Feb 20;30(6):890-905. doi: 10.1089/ars.2017.7445. Epub 2018 Feb 7.


Increasing evidence has indicated critical roles of nicotinamide adenine dinucleotide, oxidized form (NAD+) in various biological functions. NAD+ deficiency has been found in models of a number of diseases such as cerebral ischemia, myocardial ischemia, and diabetes, and in models of aging. Applications of NAD+ or other approaches that can restore NAD+ levels are highly protective in these models of diseases and aging. NAD+ produces its beneficial effects by targeting at multiple pathological pathways, including attenuating mitochondrial alterations, DNA damage, and oxidative stress, by modulating such enzymes as sirtuins, glyceraldehyde-3-phosphate dehydrogenase, and AP endonuclease. These findings have suggested great therapeutic and nutritional potential of NAD+ for diseases and senescence. Recent Advances: Approaches that can restore NAD+ levels are highly protective in the models of such diseases as glaucoma. The NAD+ deficiency in the diseases and aging results from not only poly(ADP-ribose) polymerase-1 (PARP-1) activation but also decreased nicotinamide phosphoribosyltransferase (Nampt) activity and increased CD38 activity. Significant biological effects of extracellular NAD+ have been found. Increasing evidence has suggested that NAD+ deficiency is a common central pathological factor in a number of diseases and aging. Critical Issues and Future Directions: Future studies are required for solidly establishing the concept that "NAD+ deficiency is a common central pathological factor in a number of disease and aging." It is also necessary to further investigate the mechanisms underlying the NAD+ deficiency in the diseases and aging. Preclinical and clinical studies should be conducted to determine the therapeutic potential of NAD+ for the diseases and aging.

Keywords: NAD; aging; cell death; diseases; tissue injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / drug effects
  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology
  • Humans
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / pathology
  • NAD / deficiency*
  • NAD / metabolism
  • NAD / pharmacology
  • NAD / therapeutic use*
  • Signal Transduction / drug effects


  • NAD