NAD+ and sirtuins in aging and disease

Shin ichiro Imai, Leonard Guarente

Research output: Contribution to journalReview article

484 Scopus citations

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.

Original languageEnglish
Pages (from-to)464-471
Number of pages8
JournalTrends in Cell Biology
Volume24
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Nicotinamide mononucleotide
  • Nicotinamide phosphoribosyltransferase
  • Nicotinamide riboside
  • Poly-ADP-ribose polymerases
  • Sirtuins

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