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Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002. Epub 2014 Apr 29.

NAD+ and sirtuins in aging and disease.

Author information

  • 1Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: imaishin@wustl.edu.
  • 2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Glenn Laboratory for the Science of Aging, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: leng@mit.edu.

Abstract

Nicotinamide adenine dinucleotide (NAD(+)) is a classical coenzyme mediating many redox reactions. NAD(+) also plays an important role in the regulation of NAD(+)-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD(+) levels decline during the aging process and may be an Achilles' heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.

KEYWORDS:

NAD(+); nicotinamide mononucleotide; nicotinamide phosphoribosyltransferase; nicotinamide riboside; poly-ADP-ribose polymerases; sirtuins

PMID:
24786309
PMCID:
PMC4112140
DOI:
10.1016/j.tcb.2014.04.002
[PubMed - indexed for MEDLINE]
Free PMC Article
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