The therapeutic perspective of NAD+ precursors in age-related diseases

Tooba Iqbal, Takashi Nakagawa*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Nicotinamide adenine dinucleotide (NAD+) is the fundamental molecule that performs numerous biological reactions and is crucial for maintaining cellular homeostasis. Studies have found that NAD+ decreases with age in certain tissues, and age-related NAD+ depletion affects physiological functions and contributes to various aging-related diseases. Supplementation of NAD+ precursor significantly elevates NAD+ levels in murine tissues, effectively mitigates metabolic syndrome, enhances cardiovascular health, protects against neurodegeneration, and boosts muscular strength. Despite the versatile therapeutic functions of NAD+ in animal studies, the efficacy of NAD+ precursors in clinical studies have been limited compared with that in the pre-clinical study. Clinical studies have demonstrated that NAD+ precursor treatment efficiently increases NAD+ levels in various tissues, though their clinical proficiency is insufficient to ameliorate the diseases. However, the latest studies regarding NAD+ precursors and their metabolism highlight the significant role of gut microbiota. The studies found that orally administered NAD+ intermediates interact with the gut microbiome. These findings provide compelling evidence for future trials to further explore the involvement of gut microbiota in NAD+ metabolism. Also, the reduced form of NAD+ precursor shows their potential to raise NAD+, though preclinical studies have yet to discover their efficacy. This review sheds light on NAD+ therapeutic efficiency in preclinical and clinical studies and the effect of the gut microbiota on NAD+ metabolism.

Original languageEnglish
Article number149590
JournalBiochemical and Biophysical Research Communications
Volume702
DOIs
StatePublished - 2024/04/02

Keywords

  • Aging
  • Gut microbiota
  • NAD
  • NAD precursors
  • Nicotinamide mononucleotide NMN
  • Nicotinamide riboside NR

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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